Resilience in times of Early Modern financial crises: the case study of Simon Ruiz network, 1553-1606

<p>In Spanish second half of the 16th century, a merchant called Simon Ruiz had built a network of business partners which allowed him to be one of the wealthiest merchants in the Iberia Peninsula. The Spanish Empire maintained military conflicts with almost all Europe, which further contributed to the insolvency of the Spanish Crown, resulting in three different bankruptcies (1557, 1575 and 1596) and several constraints in financial and commercial activity. In such troubled periods, trust in credit affairs was at stake and directly interfered with the liquidity of commercial firms. Hence, it is no surprise that several companies in Europe, defaulted.</p> <p>In this conjuncture, Simon Ruiz’s company and business network has not collapsed, maintaining its activity for 53 years. How and why did this business network resist to such contrarieties? In this paper, it is argued how the resilience of the network was fostered in two distinct, but complementary approaches: on one hand, the business strategies Ruiz used to face different economic conjunctures; on the other hand, the structural characteristics of the network, using variables of mathematical network analysis. Which strategies could prevent an Early Modern business company from collapse in an adverse economic scenario? We believe network analysis can contribute for the answer. To approach these questions, we will support our analysis on the bills of exchange and the commercial correspondence of Simon Ruiz private archive.</p

Schematic representation of P-cadherin positive and negative breast cancer histological types

<p><b>Copyright information:</b></p><p>Taken from "P-cadherin expression in breast cancer: a review"</p><p>http://breast-cancer-research.com/content/9/5/214</p><p>Breast cancer research : BCR 2007;9(5):214-214.</p><p>Published online 31 Oct 2007</p><p>PMCID:PMC2242663.</p><p></p> In normal breast, P-cadherin is only expressed by myoepithelial cells and not by luminal epithelial cells. In the low-grade arm of breast carcinomas, the majority of lesions are negative for P-cadherin expression, such as invasive lobular carcinomas (ILC), tubular carcinomas, and well differentiated ductal carcinoma (DCIS) and invasive ductal carcinomas (IDC). In the other arm, high-grade lesions are frequently positive for this cadherin, including the medullary carcinomas, a subset of poor-differentiated DCIS and IDC, and the metaplastic carcinomas, which represent a clear subtype of basal-like carcinomas

Supplementary Material to Structural and temporal patterns of the first global trading market

Additional Data description and analysis comprising 12 pages, 7 Figures and 2 Table

Azurin impairs invasion of breast cancer cells over-expressing P-cadherin.

<p>a) Schematic representation of the invasive profile of cell lines used in this work (upper panel) and E- and P-cadherin protein expression levels for each cell line (lower panel) b) Azurin decreases invasion of MCF-7/AZ.Pcad and SUM149 cells. Matrigel Invasion Assays showed that one single treatment of azurin at 50 µM for 48 h (MCF-7/AZ.Mock and MCF-7/AZ.Pcad) or 24 h (SUM149) significantly reduced the invasive behaviour of breast cancer cells.MCF-7/AZ.Mock cell line was used as a control and the invasion of this cell line was used to normalize the levels of invasion. c) Cell viability assessed with MTT assay of MCF-7/AZ.Mock, MCF-7/AZ.Pcad and SUM149 cell lines in the presence of azurin. Cells were plated in 96-well plates in the presence of 50 and 100 µM of azurin for 24 h (SUM149) or 48 h (MCF-7/AZ.Mock and MCF-7/AZ.Pcad) to match the time course of invasion assays for each cell line. Control cells received complete media without azurin.</p

Effect of azurin in FAK-Src signaling.

<p>Azurin at 50 µM and 100 µM decreased phosphorylation levels of FAK Y397 and Src Y416 in both MCF-7/AZ.Pcad and SUM149 breast cancer cells, but not Akt S473, in a dose-dependent manner. Levels for total FAK, Src and Akt were also analyzed. Results are presented as the ratio of band intensity of target protein between azurin treated samples and control samples, both normalized to their respective actin band intensity.</p

Azurin induced a decrease sPcad levels and MMP2 activity.

<p>Treatments with azurin (100 µM) leads to decreased levels of the pro-invasive soluble form P- Cadherin in the conditioned media of cultured cells, as observed by Western Blot, for both MCF-7/AZ.Pcad (a) and SUM149 (b). Gelatin zymography allowed the identification of MMP2 activity in the conditioned media of MCF-7/AZ.Pcad (c) and SUM149 (d) cells grown in a collagen type I matrix.</p

C/EBPβ physical interaction with the <i>CDH3</i> gene promoter.

<p><b>A</b>) Putative C/EBPβ-binding sites within the <i>CDH3</i> gene promoter, where it can be observed their degree of conservation between human and other primates. Grey regions represent total sequence conservation in comparison with human sequence; <b>B</b>) Proximal regulatory region of <i>CDH3</i> promoter displaying the relative localization of the predicted C/EBPβ binding sites (left panel). The right panel illustrates the enrichment (relative to input) of the <i>CDH3</i> promoter DNA-amplified fragments precipitated from DNA-protein complexes obtained by ChIP in MCF-7/AZ breast cancer cells. <b>C</b>) ChIP experiment performed in BT-20 breast cancer cells and on a frozen primary breast tumour, highly positive for P-cadherin and C/EBPβ expression, also showed the same enrichment pattern for all the putative binding sites.</p

Azurin decreases P-cadherin protein levels.

<p>a) One single treatment with azurin at 50 µM and 100 µM for 48 h (MCF-7/AZ.Pcad) and 24 h (SUM149) (to match the time course of invasion assays) reduces the P-cadherin expression by Western Blot with no significant alteration at E-cadherin levels. Results are presented as the ratio of band intensity of target protein between azurin treated samples and control samples, both normalized to their respective actin band intensity b) Same results were observed by immunofluorescence analysis of both cadherins in the same treatment conditions. c) Azurin does not significantly change the expression levels of <i>CDH1</i>/E-cadherin or <i>CDH3</i>/P-cadherin at mRNA levels, as observed by qRT-PCR at the same conditions as for Westerm Blot analysis.</p

Association and regulatory interplay between C/EBPβ and <i>CDH3</i>/P-cadherin expression in breast cancer cells.

<p><b>A</b>) Double immunostaining for C/EBPβ and P-cadherin of an invasive breast carcinoma specimen (basal-like carcinoma, histological grade III), where it can be observed C/EBPβ expression in the nuclei and P-cadherin at the cell membrane of tumour cells (magnification ×200 and ×400-inset); a haematoxylin-eosin staining of this same case is shown to ascertain tissue integrity (magnification ×100); <b>B</b>) Using C/EBPβ-targeted siRNA, a consequent reduction of P-cadherin protein levels was observed in both MCF-7/AZ and BT-20 breast cancer cell lines; <b>C</b>) MCF-7/AZ cells transiently transfected with the different C/EBPβ isoforms (LAP1, LAP2 and LIP) displayed upregulation of P-cadherin protein levels only after induction of the C/EBPβ-LIP isoform; <b>D</b>) Luciferase reporter assays performed in cells transfected with the different C/EBPβ isoforms showed that the promoter activation induced by LIP and LAP1 isoforms was significantly greater compared with the activation induced by LAP2. The co-transfection of both LIP and each LAP1 or LAP2 induced the activation of the <i>CDH3</i> promoter in an additive manner.</p