Basic Incompatibilities Between Evolutionary and Behavioral Archaeology

Schiffer (1996) recently proposed that, despite some incompatibilities, considerable common ground exists between behavioral archaeology and evolutionary or selectionist, archaeology. He concludes that there is no fundamental reason why the two approaches cannot work in concert to explain human behavioral change. There are, however, several important reasons why the two programs, at least as currently conceived, cannot work together in any thoroughly integrated fashion. Although both programs employ inference, behavioral archaeology conflates the distinct roles of configurational and immanent properties, searches for nomothetic answers to questions about human behavior, overlooks historical contingency when inferring and explaining the nature of past behavior, and in some cases seems to fall back on vitalism as the mechanism of change. Evolutionary archaeology employs immanent properties inferentially, explicitly acknowledges the importance of the historical contingencies of configurational properties, explains human behavior as being time- and spacebound, and calls upon selection and drift (transmission) as the mechanisms of change. Any attempt to integrate the two approaches must begin by addressing these basic differences

The use of β-cell transcription factors in engineering artificial β cells from non-pancreatic tissue

Type 1 diabetes results from the autoimmune destruction of the insulin-producing pancreatic beta (β) cells. Patients with type 1 diabetes control their blood glucose levels using several daily injections of exogenous insulin; however, this does not eliminate the long-term complications of hyperglycaemia. Currently, the only clinically viable treatments for type 1 diabetes are whole pancreas and islet transplantation. As a result, there is an urgent need to develop alternative therapies. Recently, cell and gene therapy have shown promise as a potential cure for type 1 diabetes through the genetic engineering of 'artificial' β cells to regulate blood glucose levels without adverse side effects and the need for immunosuppression. This review compares putative target cells and the use of pancreatic transcription factors for gene modification, with the ultimate goal of engineering a glucose-responsive 'artificial' β cell that mimics the function of pancreatic β cells, while avoiding autoimmune destruction

The Connection between Ultraviolet and X-ray Outflows in AGN: the case of PDS 456

High-velocity outflows from AGN are a well-known phenomena in terms of the Broad Absorption Lines seen in the UV/optical. More recently, similar, possibly related, outflows have been reported in the X-ray. The most extreme example is seen in the nearby, luminous QSO PDS 456, which displays a massive, high velocity (50000 km s-1), high-ionization X-ray outflow of 10 solar masses yr-1. Here we present the UV spectrum of PDS 456 as observed by the Hubble Space Telescope. We find the UV spectrum is also extreme, displaying very broad emission-lines, with CIV 1549 blueshifted by 5000 km s-1 and a broad Ly-alpha absorption trough blueshifted by 14000-24000 km s-1. No strong, broad high-ionization absorption features are seen. We interpret the combined UV and X-ray spectrum of PDS 456 as the signature of a decelerating, cooling outflow, which may be driven by radiation and/or magnetic field. This outflow may be the source of some of the broad emission and absorption-line gas.Comment: Accepted for publication in MNRAS. 6 pages. 6 figure

Frequent somatic mutations of GNAQ in uveal melanoma and blue naevi.

BRAF and NRAS are common targets for somatic mutations in benign and malignant neoplasms that arise from melanocytes situated in epithelial structures, and lead to constitutive activation of the mitogen-activated protein (MAP) kinase pathway. However, BRAF and NRAS mutations are absent in a number of other melanocytic neoplasms in which the equivalent oncogenic events are currently unknown. Here we report frequent somatic mutations in the heterotrimeric G protein alpha-subunit, GNAQ, in blue naevi (83%) and ocular melanoma of the uvea (46%). The mutations occur exclusively in codon 209 in the Ras-like domain and result in constitutive activation, turning GNAQ into a dominant acting oncogene. Our results demonstrate an alternative route to MAP kinase activation in melanocytic neoplasia, providing new opportunities for therapeutic intervention

The effect of Candida albicans, Actinomyces naeslundii and Streptococcus mutans biofilm effluent on the expression of interleukin-6 and interleukin-8 from normal and oral cancer cell lines

Abstract: Oral cancer is the sixth most common cancer worldwide. It is suggested that polymicrobial infection may involve in oral carcinogenesis. This study aimed to determine the effect of mono-culture and polymicrobial biofilms effluent from C. albicans, Streptococcus mutans and Actinomyces naeslundii to the expression of Interleukin-6 (IL-6) and Interleukin-8 (IL-8) from normal and oral squamous cell carcinoma (OSCC) cell lines, with the hypothesis that biofilm effluent promote oral carcinogenesis. OKF6 cell line isolated from healthy oral cavity was grown to 80% confluent in 12-well plate and incubated with 80% (v/v) serum free medium (SFM) containing biofilm effluent from mono-culture of C. albicans (ALC3), S. mutans (SM), A. naelundii (AN) or polymicrobial (TRI) for 2 h and 24 h. Incubation of the cell line with 100% SFM (NE) was conducted to represent the negative control. To quantify the amount of IL-6 and IL-8 secreted by epithelial cells in response to biofilm effluent, the conditioned medium was collected and analysed using Bio-Plex protein array system and Bio-Rad cytokine multi-plex panel. Similar protocol was repeated with H357 cell line that was isolated from patient with OSCC. The results showed that OKF6 cell line that was incubated with ALC3 had significant decrease IL-8 expression while incubation with SM exhibited significantly increase IL-6 expression when compared to NE after 2 h incubation (P<0.05). In addition, significant increase of IL-6 and IL-8 expression were observed after 24 h incubation of OKF6 cell line with TRI effluent when compared to NE (P<0.05). The incubation of H357 with AN, SM and TRI effluent exhibited significant increase of IL-6 and IL-8 expression after 2 h incubation, whereas significant increase of the similar cytokines were observed when incubated with all effluent after 24 h in comparison to NE (P<0.05). In conclusion, biofilm effluent promotes malignant phenotype of OSCC cell line

The effect of polymicrobial interaction on the adhesion of OKF6 and H357 cell lines

Introduction: Oral cancer is classified as the sixth most common cancer in the world. It has been suggested that polymicrobial infection may have a role in oral carcinogenesis. Objective: To determine the effect of mono-culture and polymicrobial biofilms effluent from C. albicans, Streptococcus mutans and Actinomyces naeslundii to the adhesion of normal and oral cancer cell lines on extra-cellular matrix (ECM) molecules coated surfaces. Methods: Initially, OKF6 cell line isolated from healthy oral cavity was incubated in serum free medium containing effluent from mono-culture or polymicrobial biofilms of C. albicans (ALC3), S. mutans (Ingbritt), A. naelundii (NCTC 10301) for 90 minutes. Following that, the suspension was added into CytoSelect 48-well Cell Adhesion Assay ECM Array kit to determine the adhesion of the cell to fibronectin, collagen I, collagen IV, laminin and fibrinogen. Fold change of adhesion of the cells incubated in biofilm effluent in comparison to that incubated in non-effluent (NE) was enumerated. Similar protocol was repeated with H357 cell line that was isolated from patient with oral squamous cell carcinoma (OSCC). Results: The majority of OKF6 cells incubated in biofilm effluent exhibited significantly decreased adhesion to ECM molecules compared to the cells incubated in NE (P<0.05). Only when incubated with S. mutans effluent, OKF6 cells exhibited significant increase in adhesion to fibronectin (P<0.05). The incubation of H357 with C. albicans effluent exhibited significant increase of adhesion to collagen IV and laminin I when compared to NE (P < 0.05). Furthermore, the adhesion of H357 cells to laminin I were also found to increase when incubated with C. albicans (15.07-fold), S. mutans (6.54-fold), A. naeslundii (1.31-fold) and polymicrobial biofilms (10.69-fold) effluents. Conclusions: The adhesion of OKF6 and H357 to ECM are biofilm effluent-dependent and that biofilm effluent enhance the malignant phenotype of H357 when grown in medium containing biofilms effluent

A new model of cosmogenic production of radiocarbon 14C in the atmosphere

We present the results of full new calculation of radiocarbon 14C production in the Earth atmosphere, using a numerical Monte-Carlo model. We provide, for the first time, a tabulated 14C yield function for the energy of primary cosmic ray particles ranging from 0.1 to 1000 GeV/nucleon. We have calculated the global production rate of 14C, which is 1.64 and 1.88 atoms/cm2/s for the modern time and for the pre-industrial epoch, respectively. This is close to the values obtained from the carbon cycle reservoir inventory. We argue that earlier models overestimated the global 14C production rate because of outdated spectra of cosmic ray heavier nuclei. The mean contribution of solar energetic particles to the global 14C is calculated as about 0.25% for the modern epoch. Our model provides a new tool to calculate the 14C production in the Earth's atmosphere, which can be applied, e.g., to reconstructions of solar activity in the past.Comment: Published in EPSL, 337, 114, 201

Ex vivo expansion of murine MSC impairs transcription factor-induced differentiation into pancreatic β-cells

© 2019 Dario Gerace et al. Combinatorial gene and cell therapy as a means of generating surrogate β-cells has been investigated for the treatment of type 1 diabetes (T1D) for a number of years with varying success. One of the limitations of current cell therapies for T1D is the inability to generate sufficient quantities of functional transplantable insulin-producing cells. Due to their impressive immunomodulatory properties, in addition to their ease of expansion and genetic modification ex vivo, mesenchymal stem cells (MSCs) are an attractive alternative source of adult stem cells for regenerative medicine. To overcome the aforementioned limitation of current therapies, we assessed the utility of ex vivo expanded bone marrow-derived murine MSCs for their persistence in immune-competent and immune-deficient animal models and their ability to differentiate into surrogate β-cells. CD45-/Ly6+ murine MSCs were isolated from the bone marrow of nonobese diabetic (NOD) mice and nucleofected to express the bioluminescent protein, Firefly luciferase (Luc2). The persistence of a subcutaneous (s.c.) transplant of Luc2-expressing MSCs was assessed in immune-competent (NOD) (n=4) and immune-deficient (NOD/Scid) (n=4) animal models of diabetes. Luc2-expressing MSCs persisted for 2 and 12 weeks, respectively, in NOD and NOD/Scid mice. Ex vivo expanded MSCs were transduced with the HMD lentiviral vector (MOI = 10) to express furin-cleavable human insulin (INS-FUR) and murine NeuroD1 and Pdx1. This was followed by the characterization of pancreatic transdifferentiation via reverse transcriptase polymerase chain reaction (RT-PCR) and static and glucose-stimulated insulin secretion (GSIS). INS-FUR-expressing MSCs were assessed for their ability to reverse diabetes after transplantation into streptozotocin- (STZ-) diabetic NOD/Scid mice (n=5). Transduced MSCs did not undergo pancreatic transdifferentiation, as determined by RT-PCR analyses, lacked glucose responsiveness, and upon transplantation did not reverse diabetes. The data suggest that ex vivo expanded MSCs lose their multipotent differentiation potential and may be more useful as gene therapy targets prior to expansion