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The article, published in the first number of the new series of East & West journal edited by ISMEO, analyses all the archaeological and historical data available to date for the Dashtestan county from the Achaemenid period, in order to demonstrate the presence of the settlement of Tamukkan (Taoce, Taḫ(u)makka) in this area and propose for it an urban model similar to that recently hypothesized for the Achaemenid settlements of Persepolis and Pasargadae. The author examines the data of the ex...

The neurotrophin Brain-derived neurotrophic factor (BDNF) is encoded by multiple bipartite transcripts. Each BDNF transcript is composed by one out of eleven alternatively spliced exons containing the 5’untranslated region (UTR), and one common exon encompassing the coding sequence (CDS) and the 3’UTR with two variants (short and long). In neurons, BDNF mRNA variants have a distinct subcellular distribution, constituting a “spatial code”, with exon 1, 3, 5, 7 and 8 located in neuronal somata, exon 4 extending into proximal dendrites, and exon 2 and 6 reaching distal dendrites. We previously showed that the CDS encodes constitutive dendritic targeting signals (DTS) and that both the 3’UTR-short and the 3’UTR-long contain activity-dependent DTS. However, the role of individual 5’UTR exons in mRNA sorting remains unclear. Here, we tested the ability of each different BDNF 5'UTRs to affect the subcellular localization of the green fluorescent protein (GFP) reporter mRNA. We found that exon 2 splicing isoforms (2a, 2b, and 2c) induced a constitutive dendritic targeting of the GFP reporter mRNA towards distal dendritic segments. The other isoforms did not affect GFP-mRNA dendritic trafficking. Through a bioinformatic analysis, we identified five unique cis-elements in exon 2a, 2b, and 2c which might contribute to building a DTS. This study provides additional information on the mechanism regulating the cellular sorting of BDNF mRNA variants.

Attraverso l’analisi di settimanali illustrati, film, programmi televisivi, reportages di viaggio, questa tesi vuole offrire un’ampia panoramica sulle rappresentazioni africane più diffuse nella società italiana degli anni Sessanta. L’indagine considera un decennio di transizione sia per l’Italia che per l’Africa: mentre la prima, dopo aver perso Libia, Eritrea ed Etiopia durante la Seconda guerra mondiale, termina l’amministrazione fiduciaria in Somalia, la seconda è attraversata dalle lotte di liberazione e celebra la nascita dei nuovi Stati indipendenti, finalmente libera di immaginarsi svincolata dalle ingerenze europee. I casi studio presentati fanno emergere i vari aspetti dello sguardo italiano al continente africano: reticente nel riconoscere le potenzialità dei nuovi Stati e ancora viziato da una forte componente esotica e coloniale, fatica a considerare l’Africa parte della Storia mondiale, ritenendola ancora semplice meta per eccellenza delle fughe esotiche occidentali. Per quanto riguarda gli ex territori coloniali italiani, essi fanno molto spesso la loro apparizione sulle pagine delle riviste perché sfondo necessario per i racconti delle gesta eroiche dell’esercito italiano in Libia e in Africa Orientale. A queste rappresentazioni ne vengono affiancate altre, più marginali e militanti, che rivelano altri modi attraverso i quali l’immagine del Continente circolasse nei media del periodo: l’Africa e il suo desiderio di futuro, esempio per i vari soggetti rivoluzionari globali, pienamente inserita nella Storia, e l’Africa come continente in movimento, finalmente liberato dall’immobilità del mito., Through the analysis of illustrated magazines, films, television programmes, travelogues, this thesis aims to offer a broad overview on the most widespread representations of Africa in 1960s Italian society. The study examines a decade of transition for both Italy and Africa: while the former, after losing Libya, Eritrea and Ethiopia during the Second World War, ends its trusteeship in Somalia, the latter is in the midst of liberation struggles and celebrates the birth of the new independent states, finally free to imagine itself emancipated from European influence. The case studies presented highlight the various aspects of the Italian view on the African continent: reluctant to recognise the potential of the new states and still marked by a strong exotic and colonial component, it struggles to consider Africa as part of world history, still holding it to be a simple destination par excellence for exotic Western escapes. As far as the former Italian colonial territories are concerned, they very often appear in the pages of magazines as a necessary background for the stories of the heroic deeds of the Italian army in Libya and East Africa. Alongside these representations are other, more marginal and militant ones, which reveal other ways in which the image of the Continent circulated in the media of the period: Africa and its desire for the future, an example for the various global revolutionary actors, fully embedded in History, and Africa as a continent in motion, finally freed from the immobility of myth.

Background COVID-19 is a deadly pulmonary disease with peculiar characteristics, which include variable clinical course and thrombophilia. A thorough understanding of the pathological correlates of the disease is still missing. Methods Here we report the systematic analysis of 41 consecutive post-mortem samples from individuals who died of COVID-19. Histological analysis is complemented by immunohistochemistry for cellular and viral antigens and the detection of viral genomes by in situ RNA hybridization. Findings COVID-19 is characterized by extensive alveolar damage (41/41 of patients) and thrombosis of the lung micro- and macro-vasculature (29/41, 71%). Thrombi were in different stages of organization, consistent with their local origin. Pneumocytes and endothelial cells contained viral RNA even at the later stages of the disease. An additional feature was the common presence of a large number of dysmorphic pneumocytes, often forming syncytial elements (36/41, 87%). Despite occasional detection of virus-positive cells, no overt signs of viral infection were detected in other organs, which showed non-specific alterations. Interpretation COVID-19 is a unique disease characterized by extensive lung thrombosis, long-term persistence of viral RNA in pneumocytes and endothelial cells, along with the presence of infected cell syncytia. Several of COVID-19 features might be consequent to the persistence of virus-infected cells for the duration of the disease. Funding This work was supported by a King's Together Rapid COVID-19 Call grant from King's College London. MG is supported by the European Research Council (ERC) Advanced Grant 787971 "CuRE" and by Programme Grant RG/19/11/34633 from the British Heart Foundation.

Il testo presenta le attività della Joint Iranian-Italian Archaeological Mission in Fars (ICAR & Alma Mater Studiorum, Università di Bologna) e, in particolare, il nuovo progetto "Land of Persepolis", dedicato alla ricostruzione diacronica del paesaggio archeologico nella piana di Persepolis.

Vortioxetine is a novel multimodal antidepressant that modulates a wide range of neurotransmitters throughout the brain. Preclinical and clinical studies have shown that vortioxetine exerts positive effects on different cognitive domains and neuroprotective effects. Considering the key role of microglial cells in brain plasticity and cognition, we aimed at investigating the effects of pretreatment with vortioxetine in modulating behavioral and molecular effects induced by an immune challenge: peripheral injection of lipopolysaccharide (LPS). To this purpose, C57BL/6J male mice were first exposed to a 28-day standard diet or vortioxetine-enriched diet, which was followed by an acute immune challenge with LPS. Sickness symptoms and depressive-like behaviors (anhedonia and memory impairment) were tested 6 and 24 h after exposure to LPS, respectively. Moreover, the expressions of markers of immune activation and M1/M2 markers of microglia polarization were measured in the dorsal and ventral parts of the hippocampus. The pretreatment with vortioxetine did not affect both LPS-induced sickness behavior and anhedonia but prevented the deficit in the recognition memory induced by the immune challenge. At the transcriptional level, chronic exposure to vortioxetine did not prevent LPS-induced upregulation of proinflammatory cytokines 6 h after the immune challenge but rather seemed to potentiate the immune response to the challenge also by affecting the levels of expression of markers of microglia M1 phenotype, like cluster of differentiation (CD)14 and CD86, in an area-dependent manner. However, at the same time point, LPS injection significantly increased the expression of the M2 polarization inducer, interleukin 4, only in the hippocampus of animals chronically exposed to vortioxetine. These results demonstrate that a chronic administration of vortioxetine specifically prevents LPS-induced memory impairment, without affecting acute sickness behavior and anhedonia, and suggest that hippocampal microglia may represent a cellular target of this novel antidepressant medication. Moreover, we provide a useful model to further explore the molecular mechanisms specifically underlying cognitive impairments following an immune challenge.

The article, published in the first number of the new series of East & West journal edited by ISMEO, proposes an innovative methodology, based on pattern recognition techniques, for the study of the metal arrowheads, and a new typology mainly focused on materials dated between the 6th and 4th century BCE. The authors propose a first pilot study, part of a larger project still underway, in which 167 arrowheads from the sites of Persepolis, Tol-e Ajori and Susa are taken into consideration. Eac...

The article, published in the first number of the new series of East & West journal edited by ISMEO, analyses all the archaeological and historical data available to date for the Dashtestan county from the Achaemenid period, in order to demonstrate the presence of the settlement of Tamukkan (Taoce, Taḫ(u)makka) in this area and propose for it an urban model similar to that recently hypothesized for the Achaemenid settlements of Persepolis and Pasargadae. The author examines the data of the ex...

Additional file 4. Recognition sequences and p values of the bioinformatic analysis of each 5’UTR BDNF exon using RBPmap database.

Additional file 2. FASTA sequences of the 5′UTR BDNF exons used in the bioinformatic analysis.

Paolo Ognibene presents a rich overview of the Greek texts dealing with Scythians, discussing the different visions that emerge from these sources and how the Greek vision of these populations evolved, starting from an initial focus on the characteristics of justice and equality in their society, to then emphasise their more violent and ferocious characters. Based on the Greek sources and the few Persian sources available, the author also tries to analyse, beyond the difficulties in correctly...

COVID-19 is a deadly pulmonary disease with unique clinical features. A thorough understanding of the molecular and histological correlates of the disease is still missing, especially because post-mortem analysis of COVID-19-affected organs has been so far scant and often anecdotical. Here we report the results of the systematic analysis of 41 consecutive post-mortem samples from individuals who died of COVID-19. We found that the disease is characterized by extensive alveolar damage and thrombosis of the lung micro- and macro-vasculature. Thrombi were in different stages of organization, consistent with an ongoing, endogenous thrombotic process. In all the analyzed samples, in situ RNA hybridization showed that pneumocytes and vascular endothelial cells had massive presence of viral RNA even at the later stages of the disease. An additional feature of the disease was the presence, in the vast majority of patients, of a large number of dysmorphic pneumocytes, often forming large syncytial elements, a consequence of the fusogenic activity of the viral Spike protein, detected with specific antibodies. Despite occasional presence of virus-positive cells in the heart, no overt signs of viral infection were detected in other organs, which showed common alterations compatible with prolonged hypoxia, multifocal organ disease or previous comorbidities. In summary, COVID-19 is a unique interstitial pneumonia with extensive lung thrombosis, long-term persistence of viral replication in pneumocytes and endothelial cells, along with the presence of infected cellular syncytia in the lung. We propose that several of the COVID-19 disease features are due to the persistence of virus-infected cells in the lungs of the infected individuals for the duration of the disease.

With the increased prevalence of chronic diseases, non-healing wounds place a significant burden on the health system and the quality of life of affected patients. Non-healing wounds are full-thickness skin lesions that persist for months or years. While several factors contribute to their pathogenesis, all non-healing wounds consistently demonstrate inadequate vascularization, resulting in the poor supply of oxygen, nutrients, and growth factors at the level of the lesion. Most existing therapies rely on the use of dermal substitutes, which help the re-epithelialization of the lesion by mimicking a pro-regenerative extracellular matrix. However, in most patients, this approach is not efficient, as non-healing wounds principally affect individuals afflicted with vascular disorders, such as peripheral artery disease and/or diabetes. Over the last 25 years, innovative therapies have been proposed with the aim of fostering the regenerative potential of multiple immune cell types. This can be achieved by promoting cell mobilization into the circulation, their recruitment to the wound site, modulation of their local activity, or their direct injection into the wound. In this review, we summarize preclinical and clinical studies that have explored the potential of various populations of immune cells to promote skin regeneration in non-healing wounds and critically discuss the current limitations that prevent the adoption of these therapies in the clinics.

The commemorative monument of Paikuli was built by the Sasanian king Narseh (293-302 / 3 AD) next to the southern pass of the Qaradagh mountain range, about 100 km from the nowadays city of Sulaimaniyah. The bilingual inscription (Middle Persian and Parthian), originally engraved on two walls of the structure, specifies both the choice of the site and the historical context related to the monument construction. This epigraphic evidence represents indeed one of the most significant internal sources on the early Sassanian period. Since 2006 a joint team of Italian-Kurdish experts carried out research activities focused on the Paikuli monument and the surrounding area. Both of them are today the object of a new Sapienza scientific project, which aims to answering the many questions this outstanding site still raises among the scholarly public. It is in fact in order to enhance the understanding of this context that the current activities are focusing on the systematic documentation of the archaeological evidence and reconstruction of the Paikuli historical landscape.

Since 2006 a team of Italian archaeologists and epigraphists, led by Prof. Carlo G. Cereti (Sapienza University of Rome) surveyed and studied the commemorative monument erected by the Sasanian king Narseh (293 302 CE) next to a strategic pass of the Qaradagh Range (Sulaimaniyah Province). Through the data collected from the site and the Paikuli Collection held at the Slemani Museum, many innovative results have been achieved in the last decade. More specifically, the study of the bilingual inscription (Middle Persian and Parthian) and the massive sculptures of the king, once adorning the monument, provided significant improvement of the scholarly debate on the early Sasanian kingship. The ongoing activities include the documentation of all the blocks originally constituting the outer coating of the monument and now scattered on the slopes of the hill. The new set of archaeological data will soon shed light on different matters related to the still problematic feature of the monument structure structure

The crosstalk between endothelial cells and cardiomyocytes has emerged as a requisite for normal cardiac development, but also a key pathogenic player during the onset and progression of cardiac disease. Endothelial cells and cardiomyocytes are in close proximity and communicate through the secretion of paracrine signals, as well as through direct cell‐to‐cell contact. Here, we provide an overview of the endothelial cell–cardiomyocyte interactions controlling heart development and the main processes affecting the heart in normal and pathological conditions, including ischaemia, remodelling and metabolic dysfunction. We also discuss the possible role of these interactions in cardiac regeneration and encourage the further improvement of in vitro models able to reproduce the complex environment of the cardiac tissue, in order to better define the mechanisms by which endothelial cells and cardiomyocytes interact with a final aim of developing novel therapeutic opportunities., Cardiomyocytes (labelled in red by anti‐α‐actinin antibodies) and endothelial cells (labelled in green by anti‐CD31 antibodies) crosstalk in multiple ways, including paracrine communication (dashed arrows) through either secreted molecules or vesicles (red circles), direct cell–cell contact (hinges) and autocrine signalling (curved arrows). This crosstalk plays an important role during embryonic development, normal post‐natal life and several pathological conditions, thus representing a novel target for the treatment of cardiovascular disorders.

The Italian Archaeological Mission in Iraqi Kurdistan (MAIKI) of Sapienza University of Rome aims to study thehistorical, linguistic and cultural development of the Kurdish region. MAIKI activities are focused on the study of the archaeological stratigraphy of the Erbil Citadel and the Sasanian monument of Paikuli and its surroundings. The present article introduces the MAIKI research projects in these sites, themethodologies, themain problems and thepreliminary results obtained so far. Regarding the Erbil Citadel, MAIKI is involved, together with the High Commission for the Erbil Citadel (HCECR), in the study of the archaeological stratigraphy of the Erbil Citadel through the analysis of recent geophysical surveys and the study of the archaeological materials from the excavations carried out by the HCECR. Concerning Paikuli, the study of the site and its bilingual inscription has been flanked by the compilation of a new archaeological map of the surroundings of the Sasanian monument along the highway that links the cities of Darbandikhan and Chamchamal. Moreover, new ethnographic research aimed at studying the religious heritage of the region and a topographic study of the surveyed area have been launched. The analysis of aerial and satellite imagery, the field-walk campaigns and the study of the collected archaeological finds have provided us with significant data for the understanding of the history of the landscape and the settlements in the area. These researches will hopefully play a major role in enhancing the efforts to safeguard and protect the Cultural Heritage of the areas.

This paper discusses some astragals brought to light at Persepolis West by the Iranian-Italian Joint Archaeological Mission in Fars. The preliminary study of these findings and their archaeological contexts suggests a dating between the Achaemenian and the Arsacid periods. The possible relationship between the astragals and the deposits of bones (Tr. 6) used as fuel for a nearby kiln (Tr. 4) also appears significant.

The excavation of the urban site of Barikot (Swat, Pakistan), with its forty years of systematic archaeological activity and stratigraphic sequence from the Chalcolithic to the 20th century AD, provides a very fruitful harvest of stratigraphic data that currently has few comparisons in the subcontinent. The cross-analysis of the artefacts and the stratigraphic data, although needing constant updating, provides crucial information on the material culture in the area and on its diachronic evolution. This article presents the taxonomic study of copper alloy objects found in Trenches BKG 1, 3 and 4-5 of the Barikot site cross-compared with the most updated chronological sequence proposed for the site and based on the recent archaeological excavations.

Il testo presenta alcune ipotesi ricostruttive del sistema amministrativo arsacide basate sul confronto tra le fonti storico-epigrafiche e i dati archeologici.

The neurotrophin brain-derived neurotrophic factor (BDNF) is encoded by multiple transcripts generated by differential use of eight 50UTR exons (exons 1–8), which are alternatively spliced to the common exon (exon 9) containing the coding sequence (CDS) and the 30UTR region. Because the 30UTR sequence of BDNF contains two polyadenylation sites, each transcript has either a short or a long 30 noncoding tail, generating 22 transcripts in rodents and 32 in humans. Nonradioactive in situ hybridization techniques have allowed a detailed analysis of the expression pattern of different BDNF transcripts. These studies led to the discovery that BDNF splice variants are preferentially distributed in different subcellular compartments, including the soma (exons 1, 3, 5, 7, 8), proximal dendrites (exons 2, 4, 6), and distal dendrites (exons 2, 6), thereby creating a “spatial code” for local production of BDNF protein. More recently, generation of transgenic mice with disruption of BDNF production from single Bdnf exons has provided new insights into the role of individual Bdnf transcripts in regulating social behavior, food intake, visual plasticity, sleep, sensory information processing, and fear regulation. This chapter will provide a detailed description of methods for visualizing Bdnf transcripts, including a “classical” nonradioactive in situ hybridization (ISH) technique using digoxigenin and enzyme alkaline phosphatase (AP). In addition, it will describe more modern techniques, such as fluorescent in situ hybridization (FISH) with tyramide signal amplification and the RNAscope® Multiplex Fluorescent Assay, a FISH method that allows detection of up to four gene targets or Bdnf splice variants simultaneously.

Cardiomyocyte proliferation stops at birth when the heart is no longer exposed to maternal blood and, likewise, to regulatory T cells (Tregs) that are expanded to promote maternal tolerance towards the fetus. Here, we report a role of Tregs in promoting cardiomyocyte proliferation. Treg-conditioned medium promotes cardiomyocyte proliferation, similar to the serum from pregnant animals. Proliferative cardiomyocytes are detected in the heart of pregnant mothers, and Treg depletion during pregnancy decreases both maternal and fetal cardiomyocyte proliferation. Treg depletion after myocardial infarction results in depressed cardiac function, massive inflammation, and scarce collagen deposition. In contrast, Treg injection reduces infarct size, preserves contractility, and increases the number of proliferating cardiomyocytes. The overexpression of six factors secreted by Tregs (Cst7, Tnfsf11, Il33, Fgl2, Matn2, and Igf2) reproduces the therapeutic effect. In conclusion, Tregs promote fetal and maternal cardiomyocyte proliferation in a paracrine manner and improve the outcome of myocardial infarction., Regulatory T cells (Tregs) expand during pregnancy to promote tolerance towards the fetus. Here the authors show that Tregs induce proliferation of fetal and maternal cardiomyocytes during pregnancy and enhance myocardial repair via proliferation-promoting paracrine actions.

Transcription factors (TFs) exert their regulatory action by binding to DNA with specific sequence preferences. However, different TFs can partially share their binding sequences due to their common evolutionary origin. This `redundancy' of binding defines a way of organizing TFs in `motif families' by grouping TFs with similar binding preferences. Since these ultimately define the TF target genes, the motif family organization entails information about the structure of transcriptional regulation as it has been shaped by evolution. Focusing on the human TF repertoire, we show that a one-parameter evolutionary model of the Birth-Death-Innovation type can explain the TF empirical ripartition in motif families, and allows to highlight the relevant evolutionary forces at the origin of this organization. Moreover, the model allows to pinpoint few deviations from the neutral scenario it assumes: three over-expanded families (including HOX and FOX genes), a set of `singleton' TFs for which duplication seems to be selected against, and a higher-than-average rate of diversification of the binding preferences of TFs with a Zinc Finger DNA binding domain. Finally, a comparison of the TF motif family organization in different eukaryotic species suggests an increase of redundancy of binding with organism complexity., Comment: 14 pages, 5 figures. Minor changes. Final version, accepted for publication

Background: COVID-19 is a deadly pulmonary disease with peculiar characteristics, which include variable clinical course and thrombophilia. A thorough understanding of the pathological correlates of the disease is still missing. Methods: Here we report the systematic analysis of 41 consecutive post-mortem samples from individuals who died of COVID-19. Histological analysis is complemented by immunohistochemistry for cellular and viral antigens and the detection of viral genomes by in situ RNA hybridization. Findings: COVID-19 is characterized by extensive alveolar damage (41/41 of patients) and thrombosis of the lung micro- and macro-vasculature (29/41, 71%). Thrombi were in different stages of organization, consistent with their local origin. Pneumocytes and endothelial cells contained viral RNA even at the later stages of the disease. An additional feature was the common presence of a large number of dysmorphic pneumocytes, often forming syncytial elements (36/41, 87%). Despite occasional detection of virus-positive cells, no overt signs of viral infection were detected in other organs, which showed non-specific alterations. Interpretation: COVID-19 is a unique interstitial pneumonia characterized by extensive lung thrombosis, long-term persistence of viral RNA in pneumocytes and endothelial cells, along with the presence of infected cell syncytia. Several of COVID-19 features might be consequent to the persistence of virus-infected cells for the duration of the disease. Funding: This work was supported by a King’s Together Rapid COVID-19 Call grant from King’s College London. MG is supported by the European Research Council (ERC) Advanced Grant 787971 "CuRE" and by Programme Grant RG/19/11/34633 from the British Heart Foundation. Declaration of Interests: The authors declare no conflict of interests. Ethics Approval Statement: This study was approved by the competent Joint Ethical Committee of the Regione Friuli Venezia Giulia, Italy.