Introducció de material exòtic per a l'obtenció de blat de moro farratger: resultats preliminars

Peer Reviewe

Ionic Liquids as Reaction Media in Catalytic Oxidations with Manganese and Iron Pyridyl Triazacyclononane Complexes

A family of bioinspired iron and manganese complexes of general formula [MII(CF3SO3)2(Me,XPyTACN)], where Me,XPyTACN = 1-[2’-(6-X-pyridyl)methyl]-4,7-dimethyl-1,4,7-triazacyclononane, and M = Fe, and Mn has been studied as efficient catalytic systems for hydrogen peroxide oxidation reactions. Previous work revealed that the manganese derivative [MnII(CF3SO3)2(Me,HPyTACN)], 1, in acetonitrile exhibits a high catalytic activity in the epoxidation of a wide range of olefins (TON: 810-4500), using acetic acid and hydrogen peroxide as primary oxidant. The analogous iron based complex [FeII(CF3SO3)2(Me,HPyTACN)], 2a and [FeII(CF3SO3)2(Me,MePyTACN)], 2b promote the high added value oxidation reaction of alkanes in mild conditions. In this work sustainability and selectivity of the oxidative system is improved with the use of the ionic liquids (ILs) as reaction medium. The possibility to recycle the catalytic phase without loss of the activity with respect to the original reaction in acetonitrile (MeCN) is reported

A high-affinity antibody against the CSP N-terminal domain lacks Plasmodium falciparum inhibitory activity

Malaria is a global health concern and research efforts are ongoing to develop a superior vaccine to RTS,S/AS01. To guide immunogen design, we seek a comprehensive understanding of the protective humoral response against Plasmodium falciparum circumsporozoite protein (PfCSP). In contrast to the well-studied responses to the repeat region and the C-terminus, the antibody response against the N-terminal domain of PfCSP (N-CSP) remains obscure. Here, we characterized the molecular recognition and functional efficacy of the N-CSP-specific monoclonal antibody 5D5. The crystal structure at 1.85 Åresolution revealed that 5D5 binds an α-helical epitope in N-CSP with high affinity through extensive shape and charge complementarity, and the unusual utilization of an N-linked glycan. Nevertheless, functional studies indicated low 5D5 binding to live Pf sporozoites, and lack of sporozoite inhibition in vitro and in mosquitoes. Overall, our data on low recognition and inhibition of sporozoites do not support the inclusion of the 5D5 epitope into the next generation of CSP-based vaccines.Summary Statement The Plasmodium falciparum sporozoite surface protein, PfCSP, is an attractive vaccine target, but the antibody response against the CSP N-terminal domain has remained understudied. Here, to guide immunogen design, Thai et al. provide insights into the binding motif and functional efficacy of the N-terminal domain-specific monoclonal antibody, 5D5

Reversal by RARα agonist Am580 of c-Myc-induced imbalance in RARα/RARγ expression during MMTV-Myc tumorigenesis

Introduction Retinoic acid signaling plays key roles in embryonic development and in maintaining the differentiated status of adult tissues. Recently, the nuclear retinoic acid receptor (RAR) isotypes α, β and γ were found to play specific functions in the expansion and differentiation of the stem compartments of various tissues. For instance, RARγ appears to be involved in stem cell compartment expansion, while RARα and RARβ are implicated in the subsequent cell differentiation. We found that over-expressing c-Myc in normal mouse mammary epithelium and in a c-Myc-driven transgenic model of mammary cancer, disrupts the balance between RARγ and RARα/β in favor of RARγ. Methods The effects of c-Myc on RAR isotype expression were evaluated in normal mouse mammary epithelium, mammary tumor cells obtained from the MMTV-Myc transgenic mouse model as well as human normal immortalized breast epithelial and breast cancer cell lines. The in vivo effect of the RARα-selective agonist 4-[(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)carboxamido]benzoic acid (Am580) was examined in the MMTV-Myc mouse model of mammary tumorigenesis. Results Modulation of the RARα/β to RARγ expression in mammary glands of normal mice, oncomice, and human mammary cell lines through the alteration of RAR-target gene expression affected cell proliferation, survival and tumor growth. Treatment of MMTV-Myc mice with the RARα-selective agonist Am580 led to significant inhibition of mammary tumor growth (~90%, P\u3c0.001), lung metastasis (P\u3c0.01) and extended tumor latency in 63% of mice. Immunocytochemical analysis showed that in these mice, RARα responsive genes such as Cyp26A1, E-cadherin, cellular retinol-binding protein 1 (CRBP1) and p27, were up-regulated. In contrast, the mammary gland tumors of mice that responded poorly to Am580 treatment (37%) expressed significantly higher levels of RARγ. In vitro experiments indicated that the rise in RARγ was functionally linked to promotion of tumor growth and inhibition of differentiation. Thus, activation of the RARα pathway is linked to tumor growth inhibition, differentiation and cell death. Conclusions The functional consequence of the interplay between c-Myc oncogene expression and the RARγ to RARα/β balance suggests that prevalence of RARγ over-RARα/β expression levels in breast cancer accompanied by c-Myc amplification or over-expression in breast cancer should be predictive of response to treatment with RARα-isotype-specific agonists and warrant monitoring during clinical trials. See related editorial by Garattini et al http://breast-cancer-research.com/content/14/5/11

A new prognostic algorithm based on stage of cirrhosis and HVPG to improve risk-stratification after variceal bleeding

Background & Aims: HVPG decrease ≥20% or ≤12mmHg (“responders”) indicates good prognosis during propranolol/nadolol treatment but requires two HVPG measurements. We aimed at simplifying risk‐stratification after variceal bleeding using clinical data and HVPG. Methods: 193 cirrhotic patients (62% with ascites and/or hepatic encephalopathy, HE) included within 7‐days of bleeding had HVPG measured before and at 1‐3 months of treatment with propranolol/nadolol plus endoscopic band ligation. End‐points: Rebleeding and rebleeding/transplantation‐free survival for 4‐years. Another cohort (n=231) served as validation set. Results: During follow‐up 45 patients had variceal bleeding and 61 died. HVPG‐responders (n=71) had lower rebleeding‐risk (10% vs 34%, p=0.001) and better survival than 122 non‐responders (61% vs 39%, p=0.001). Patients with/HE (n=120) had lower survival than patients without (40% vs 63%, p=0.005). Among patients with ascites/HE, those with baseline HVPG≤16mmHg (n=16) had low rebleeding‐risk (13%). By contrast, among patients with ascites/HE and baseline HVPG>16mmHg, only HVPG‐responders (n=32) had good prognosis, with lower rebleeding‐risk and better survival than non‐responders (n=72) (respective proportions: 7% vs 39%,p=0.018; 56% vs 30% p=0.010). These findings allowed developing a new algorithm for risk‐stratification in which HVPG‐response was only measured in patients with ascites and/or HE and baseline HVPG>16mmHg. This algorithm reduced the grey‐zone (high‐risk patients not dying on follow‐up) from 46% to 35% and decreased by 42% the HVPG measurements required. The validation cohort confirmed these results. Conclusion: Restricting HVPG measurements to patients with ascites/HE and measuring HVPG‐response only if baseline HVPG>16mmHg improves detection of high‐risk patients while markedly reducing the number of HVPG measurements required

Insulin-like growth factor I (IGF-I)-induced chronic gliosis and retinal stress lead to neurodegeneration in a mouse model of retinopathy

Insulin-like growth factor I (IGF-I) exerts multiple effects on different retinal cell types in both physiological and pathological conditions. Despite the growth factor's extensively described neuroprotective actions, transgenic mice with increased intraocular levels of IGF-I showed progressive impairment of electroretinographic amplitudes up to complete loss of response, with loss of photoreceptors and bipolar, ganglion, and amacrine neurons. Neurodegeneration was preceded by the overexpression of genes related to retinal stress, acute-phase response, and gliosis, suggesting that IGF-I altered normal retinal homeostasis. Indeed, gliosis and microgliosis were present from an early age in transgenic mice, before other alterations occurred, and were accompanied by signs of oxidative stress and impaired glutamate recycling. Older mice also showed overproduction of pro-inflammatory cytokines. Our results suggest that, when chronically increased, intraocular IGF-I is responsible for the induction of deleterious cellular processes that can lead to neurodegeneration, and they highlight the importance that this growth factor may have in the pathogenesis of conditions such as ischemic or diabetic retinopathy

Sfrp3 modulates stromal-epithelial crosstalk during mammary gland development by regulating Wnt levels

Mammary stroma is essential for epithelial morphogenesis and development. Indeed, postnatal mammary gland (MG) development is controlled locally by the repetitive and bi-directional cross-talk between the epithelial and the stromal compartment. However, the signalling pathways involved in stromal–epithelial communication are not entirely understood. Here, we identify Sfrp3 as a mediator of the stromal–epithelial communication that is required for normal mouse MG development. Using Drosophila wing imaginal disc, we demonstrate that Sfrp3 functions as an extracellular transporter of Wnts that facilitates their diffusion, and thus, their levels in the boundaries of different compartments. Indeed, loss of Sfrp3 in mice leads to an increase of ductal invasion and branching mirroring an early pregnancy state. Finally, we observe that loss of Sfrp3 predisposes for invasive breast cancer. Altogether, our study shows that Sfrp3 controls MG morphogenesis by modulating the stromal-epithelial cross-talk during pubertal development

BMP7 overexpression in adipose tissue induces white adipogenesis and improves insulin sensitivity in ob/ob mice

Altres ajuts: ICREA Academia AwardBackground/objectives: During obesity, hypertrophic enlargement of white adipose tissue (WAT) promotes ectopic lipid deposition and development of insulin resistance. In contrast, WAT hyperplasia is associated with preservation of insulin sensitivity. The complex network of factors that regulates white adipogenesis is not fully understood. Bone morphogenic protein 7 (BMP7) can induce brown adipogenesis, but its role on white adipogenesis remains to be elucidated. Here, we assessed BMP7-mediated effects on white adipogenesis in ob/ob mice. Methods: BMP7 was overexpressed in either WAT or liver of ob/ob mice using adeno-associated viral (AAV) vectors. Analysis of gene expression, histological and morphometric alterations, and metabolites and hormones concentrations were carried out. Results: Overexpression of BMP7 in adipocytes of subcutaneous and visceral WAT increased fat mass, the proportion of small-size adipocytes and the expression of adipogenic and mature adipocyte genes, suggesting induction of adipogenesis irrespective of fat depot. These changes were associated with reduced hepatic steatosis and improved insulin sensitivity. In contrast, liver-specific overproduction of BMP7 did not promote WAT hyperplasia despite BMP7 circulating levels were similar to those achieved after genetic engineering of WAT. Conclusions: This study unravels a new autocrine/paracrine role of BMP7 on white adipogenesis and highlights that BMP7 may modulate WAT plasticity and increase insulin sensitivity