Melanoma-restricted genes

Human metastatic cutaneous melanoma has gained a well deserved reputation for its immune responsiveness. The reason(s) remain(s) unknown. We attempted previously to characterize several variables that may affect the relationship between tumor and host immune cells but, taken one at the time, none yielded a convincing explanation. With explorative purposes, high-throughput technology was applied here to portray transcriptional characteristics unique to metastatic cutaneous melanoma that may or may not be relevant to its immunogenic potential. Several functional signatures could be identified descriptive of immune or other biological functions. In addition, the transcriptional profile of metastatic melanoma was compared with that of primary renal cell cancers (RCC) identifying several genes co-coordinately expressed by the two tumor types. Since RCC is another immune responsive tumor, commonalities between RCC and melanoma may help untangle the enigma of their potential immune responsiveness. This purely descriptive study provides, therefore, a map for the investigation of metastatic melanoma in future clinical trials and at the same time may invite consideration of novel therapeutic targets

Selection and validation of endogenous reference genes using a high throughput approach

BACKGROUND: Endogenous reference genes are commonly used to normalize expression levels of other genes with the assumption that the expression of the former is constant in different tissues and in different physiopathological conditions. Whether this assumption is correct it is, however, still matter of debate. In this study, we searched for stably expressed genes in 384 cDNA array hybridization experiments encompassing different tissues and cell lines. RESULTS: Several genes were identified whose expression was highly stable across all samples studied. The usefulness of 8 genes among them was tested by normalizing the relative gene expression against test genes whose expression pattern was known. The range of accuracy of individual endogenous reference genes was wide whereas consistent information could be obtained when information pooled from different endogenous reference genes was used. CONCLUSIONS: This study suggests that even when the most stably expressed genes in array experiments are used as endogenous reference, significant variation in test gene expression estimates may occur and the best normalization is achieved when data from several endogenous reference genes are pooled together to minimize minimal but significant variation among samples. We are presently optimizing strategies for the preparation of endogenous reference gene mixtures that could yield information comparable to that of data pooled from individual endogenous reference gene normalizations

From the Singular to the Plural: Exploring Diversities in Contemporary Childhoods in sub-Saharan Africa

The challenges that sub-Saharan Africa has faced in the post-colonial period have come to characterise the way the region is perceived. These narratives are especially evident in the various ways children’s lives are discussed, leading to a particular focus on childhoods in difficult circumstances or at the margins. This has eclipsed the mundanities of everyday life for many children whose lives are not characterised by ‘lacks’. This article seeks to move beyond an overwhelming focus on childhoods defined by what they lack by illustrating the multitude of childhoods which exist in the continent

Robotic milking technologies and renegotiating situated ethical relationships on UK dairy farms

Robotic or automatic milking systems (AMS) are novel technologies that take over the labor of dairy farming and reduce the need for human-animal interactions. Because robotic milking involves the replacement of 'conventional' twice-a-day milking managed by people with a system that supposedly allows cows the freedom to be milked automatically whenever they choose, some claim robotic milking has health and welfare benefits for cows, increases productivity, and has lifestyle advantages for dairy farmers. This paper examines how established ethical relations on dairy farms are unsettled by the intervention of a radically different technology such as AMS. The renegotiation of ethical relationships is thus an important dimension of how the actors involved are re-assembled around a new technology. The paper draws on in-depth research on UK dairy farms comparing those using conventional milking technologies with those using AMS. We explore the situated ethical relations that are negotiated in practice, focusing on the contingent and complex nature of human-animal-technology interactions. We show that ethical relations are situated and emergent, and that as the identities, roles, and subjectivities of humans and animals are unsettled through the intervention of a new technology, the ethical relations also shift. © 2013 Springer Science+Business Media Dordrecht

Expression of genes involved in the T cell signalling pathway in circulating immune cells of cattle 24 months following oral challenge with Bovine Amyloidotic Spongiform Encephalopathy (BASE)

BACKGROUND: Bovine Amyloidotic Spongiform Encephalopathy (BASE) is a variant of classical BSE that affects cows and can be transmitted to primates and mice. BASE is biochemically different from BSE and shares some molecular and histo-pathological features with the MV2 sub-type of human sporadic Creutzfeld Jakob Disease (sCJD). RESULTS: The present work examined the effects of BASE on gene expression in circulating immune cells. Ontology analysis of genes differentially expressed between cattle orally challenged with brain homogenate from cattle following intracranial inoculation with BASE and control cattle identified three main pathways which were affected. Within the immune function pathway, the most affected genes were related to the T cell receptor-mediated T cell activation pathways. The differential expression of these genes in BASE challenged animals at 10,12 and 24 months following challenge, vs unchallenged controls, was investigated by real time PCR. CONCLUSIONS: The results of this study show that the effects of prion diseases are not limited to the CNS, but involve the immune system and particularly T cell signalling during the early stage following challenge, before the appearance of clinical signs.Andrea Trovato, Simona Panelli, Francesco Strozzi, Caterina Cambulli, Ilaria Barbieri, Nicola Martinelli, Guerino Lombardi, Rossana Capoferri and John L William

Corrigendum:“Dating the funerary use of caves in Liguria (northwestern Italy) from the Neolithic to historic times. Results from a large-scale AMS campaign on human skeletal series” [Quat. Int. 536 (2020) 30–44] (Quaternary International (2020) 536 (30–44), (S1040618219308857), (10.1016/j.quaint.2019.11.034))

In Appendix 1, and Supplementary Information Tables S1 and S2, the age class of individual [AC6726.4 (Prob. AC EIV BB)/ACN 030] is indicated as “adolescent”; the correct age class is “adult”. In Appendix 1, and Supplementary Information Tables S1 and S2, the age class of individual [AC V BB/ACN 031] is indicated as “adult”; the correct age class is “adolescent”, as also discussed in the text. The mistake does not change the results in Table 4

Cold non-ischemic heart preservation with continuous perfusion prevents early graft failure in orthotopic pig-to-baboon xenotransplantation

Background Successful preclinical transplantations of porcine hearts into baboon recipients are required before commencing clinical trials. Despite years of research, over half of the orthotopic cardiac xenografts were lost during the first 48 hours after transplantation, primarily caused by perioperative cardiac xenograft dysfunction (PCXD). To decrease the rate of PCXD, we adopted a preservation technique of cold non-ischemic perfusion for our ongoing pig-to-baboon cardiac xenotransplantation project. Methods Fourteen orthotopic cardiac xenotransplantation experiments were carried out with genetically modified juvenile pigs (GGTA1- KO/hCD46/hTBM) as donors and captive-bred baboons as recipients. Organ preservation was compared according to the two techniques applied: cold static ischemic cardioplegia (IC; n = 5) and cold non-ischemic continuous perfusion (CP; n = 9) with an oxygenated albumin-containing hyperoncotic cardioplegic solution containing nutrients, erythrocytes and hormones. Prior to surgery, we measured serum levels of preformed anti-non-Gal-antibodies. During surgery, hemodynamic parameters were monitored with transpulmonary thermodilution. Central venous blood gas analyses were taken at regular intervals to estimate oxygen extraction, as well as lactate production. After surgery, we measured troponine T and serum parameters of the recipient's kidney, liver and coagulation functions. Results In porcine grafts preserved with IC, we found significantly depressed systolic cardiac function after transplantation which did not recover despite increasing inotropic support. Postoperative oxygen extraction and lactate production were significantly increased. Troponin T, creatinine, aspartate aminotransferase levels were pathologically high, whereas prothrombin ratios were abnormally low. In three of five IC experiments, PCXD developed within 24 hours. By contrast, all nine hearts preserved with CP retained fully preserved systolic function, none showed any signs of PCXD. Oxygen extraction was within normal ranges; serum lactate as well as parameters of organ functions were only mildly elevated. Preformed anti-non-Gal-antibodies were similar in recipients receiving grafts from either IC or CP preservation. Conclusions While standard ischemic cardioplegia solutions have been used with great success in human allotransplantation over many years, our data indicate that they are insufficient for preservation of porcine hearts transplanted into baboons: Ischemic storage caused severe impairment of cardiac function and decreased tissue oxygen supply, leading to multi-organ failure in more than half of the xenotransplantation experiments. In contrast, cold non-ischemic heart preservation with continuous perfusion reliably prevented early graft failure. Consistent survival in the perioperative phase is a prerequisite for preclinical long-term results after cardiac xenotransplantation

Dating the funerary use of caves in Liguria (northwestern Italy) from the Neolithic to historic times:Results from a large-scale AMS campaign on human skeletal series

The multidisciplinary research team of this new project aimed at the chronological, anthropological and funerary behavior characterization of the skeletal remains unearthed from various caves in western Liguria (northwestern Italy) between the mid-1800s and the 1990s. Most of the burials and scattered bone assemblages were excavated prior to the development of modern stratigraphic methods, or come from disturbed contexts, often resulting in a vague chrono-cultural attribution. We present here the results of a systematic dating project that produced 130 new AMS dates on human bone samples (documented burials or individuals from scattered remains) from sixteen Ligurian caves, including most of the skeletal series from renowned sites such as Arene Candide Cave and Grotta Pollera. Results highlighted the funerary use of these caves from the last quarter of the sixth millennium BCE to the Common Era, with the majority of results clustering in the first half of the fifth millennium BCE. These dates allow for an initial assessment of patterns in Neolithic mortuary use of Ligurian caves, and aided in particular the characterization of funerary practices during the Square Mouthed Pottery culture