Histoire des drogues d'origine végétale /

v. 1

Histoire des drogues d'origine végétale /

v. 2

Spillovers and growth in a local interaction model

In this paper we aim at studying to what extent spillovers between firms may foster economic growth. The attention is addressed to the spillovers connected with the R&D activity that improves the quality of the goods firms supply. Our model develops a growth theory framework and we assume that firms spread around a circle. Our study assesses that spillovers between neighbors affect the probability of successful research for each of them. In particular, spillovers are the forces fuelling growth when, on the whole, firms turn out to be net receivers with respect to their neighbors.

En els marges de la ciència?: Frenologia i mesmerisme en una cultura industrial, Barcelona 1842-1845

L’objectiu d’aquest treball és estudiar la popularització de la frenologia i del mesmerisme (també conegut com a magnetisme animal) a la Catalunya de mitjan segle XIX. A Catalunya el procés de popularització d’aquestes ciències va tenir el seu punt àlgid durant la primera meitat de la dècada de 1840, coincidint amb les activitats del frenòleg Marià Cubí Soler (1801-1875). El treball demostra la importància del context polític i cultural, així com la incomoditat que generaven les pràctiques de frenòlegs i magnetitzadors com a elements clau per entendre les actituds de l’elit intel•lectual catalana vers la introducció d’aquestes noves ciències.

First report of Ascarophis Van Beneden, 1871: A. Brasiliensis n.sp. (Nematoda, Ascarophidinae) and Procamallanus (Spirocamallanus) Pereira/Annereaux, 1946 (Nematoda, Procamallaninae) in South America

Ascarophis brasiliensis recovered from the stomach of Trachinotus carolinus (L. 1766), is proposed as a new species and Procamallanus (Spirocamallanus) pereirai Annereaux, 1946 is redescribed from a new host: Paralonchurus brasiliensis (Steind., 1875). A. brasiliensis is more closely related to A. crassicolis Dollfus & Campana-Rouget, 1956, from which it differs mainly by the absence of cervical cuticular expansion and size of the eggs. The new species is also compared to A. cooperi johnston & Mawson, 1945 and A. girellae (Yamaguti, 1935) Campana-rouget, 1955. The validity of the proposed species is discussed.

Disaggregating chaperones: an unfolding story.

Stress, molecular crowding and mutations may jeopardize the native folding of proteins. Misfolded and aggregated proteins not only loose their biological activity, but may also disturb protein homeostasis, damage membranes and induce apoptosis. Here, we review the role of molecular chaperones as a network of cellular defenses against the formation of cytotoxic protein aggregates. Chaperones favour the native folding of proteins either as "holdases", sequestering hydrophobic regions in misfolding polypeptides, and/or as "unfoldases", forcibly unfolding and disentangling misfolded polypeptides from aggregates. Whereas in bacteria, plants and fungi Hsp70/40 acts in concert with the Hsp100 (ClpB) unfoldase, Hsp70/40 is the only known chaperone in the cytoplasm of mammalian cells that can forcibly unfold and neutralize cytotoxic protein conformers. Owing to its particular spatial configuration, the bulky 70 kDa Hsp70 molecule, when distally bound through a very tight molecular clamp onto a 50-fold smaller hydrophobic peptide loop extruding from an aggregate, can locally exert on the misfolded segment an unfolding force of entropic origin, thus destroying the misfolded structures that stabilize aggregates. ADP/ATP exchange triggers Hsp70 dissociation from the ensuing enlarged unfolded peptide loop, which is then allowed to spontaneously refold into a closer-to-native conformation devoid of affinity for the chaperone. Driven by ATP, the cooperative action of Hsp70 and its co-chaperone Hsp40 may thus gradually convert toxic misfolded protein substrates with high affinity for the chaperone, into non-toxic, natively refolded, low-affinity products. Stress- and mutation-induced protein damages in the cell, causing degenerative diseases and aging, may thus be effectively counteracted by a powerful network of molecular chaperones and of chaperone-related proteases.

Top Three Pharmacogenomics and Personalized Medicine Applications at the Nexus of Renal Pathophysiology and Cardiovascular Medicine.

Pharmacogenomics is a field with origins in the study of monogenic variations in drug metabolism in the 1950s. Perhaps because of these historical underpinnings, there has been an intensive investigation of 'hepatic pharmacogenes' such as CYP450s and liver drug metabolism using pharmacogenomics approaches over the past five decades. Surprisingly, kidney pathophysiology, attendant diseases and treatment outcomes have been vastly under-studied and under-theorized despite their central importance in maintenance of health, susceptibility to disease and rational personalized therapeutics. Indeed, chronic kidney disease (CKD) represents an increasing public health burden worldwide, both in developed and developing countries. Patients with CKD suffer from high cardiovascular morbidity and mortality, which is mainly attributable to cardiovascular events before reaching end-stage renal disease. In this paper, we focus our analyses on renal function before end-stage renal disease, as seen through the lens of pharmacogenomics and human genomic variation. We herein synthesize the recent evidence linking selected Very Important Pharmacogenes (VIP) to renal function, blood pressure and salt-sensitivity in humans, and ways in which these insights might inform rational personalized therapeutics. Notably, we highlight and present the rationale for three applications that we consider as important and actionable therapeutic and preventive focus areas in renal pharmacogenomics: 1) ACE inhibitors, as a confirmed application, 2) VDR agonists, as a promising application, and 3) moderate dietary salt intake, as a suggested novel application. Additionally, we emphasize the putative contributions of gene-environment interactions, discuss the implications of these findings to treat and prevent hypertension and CKD. Finally, we conclude with a strategic agenda and vision required to accelerate advances in this under-studied field of renal pharmacogenomics with vast significance for global public health.

Association of N-acetylaspartate and cerebrospinal fluid Aβ42 in dementia.

The interplay of amyloid and mitochondrial function is considered crucial in the pathophysiology of Alzheimer's disease (AD). We tested the association of the putative marker of mitochondrial function N-acetylaspartate (NAA) as measured by proton magnetic resonance spectroscopy within the medial temporal lobe and cerebrospinal fluid amyoid-β42 (Aβ42), total Tau and pTau181. 109 patients were recruited in a multicenter study (40 mild AD patients, 14 non-AD dementia patients, 29 mild cognitive impairment (MCI) AD-type patients, 26 MCI of non-AD type patients). NAA correlated with Aβ42 within the AD group. Since the NAA concentration is coupled to neuronal mitochondrial function, the correlation between NAA and Aβ42 may reflect the interaction between disrupted mitochondrial pathways and amyloid production.

Association between conventional risk factors and different ultrasound-based markers of atherosclerosis at carotid and femoral levels in a middle-aged population.

Ultrasound detection of sub-clinical atherosclerosis (ATS) may help identify individuals at high cardiovascular risk. Most studies evaluated intima-media thickness (IMT) at carotid level. We compared the relationships between main cardiovascular risk factors (CVRF) and five indicators of ATS (IMT, mean and maximal plaque thickness, mean and maximal plaque area) at both carotid and femoral levels. Ultrasound was performed on 496 participants aged 45-64 years randomly selected from the general population of the Republic of Seychelles. 73.4 % participants had ≥ 1 plaque (IMT thickening ≥ 1.2 mm) at carotid level and 67.5 % at femoral level. Variance (adjusted R2) contributed by age, sex and CVRF (smoking, LDL-cholesterol, HDL-cholesterol, blood pressure, diabetes) in predicting any of the ATS markers was larger at femoral than carotid level. At both carotid and femoral levels, the association between CVRF and ATS was stronger based on plaque-based markers than IMT. Our findings show that the associations between CVRF and ATS markers were stronger at femoral than carotid level, and with plaque-based markers rather than IMT. Pending comparison of these markers using harder cardiovascular endpoints, our findings suggest that markers based on plaque morphology assessed at femoral artery level might be useful cardiovascular risk predictors.

Jaume Brossa (1868-1919) regeneracionista i revolucionari

Treball de recerca realitzat per una alumna d'ensenyament secundari i guardonat amb un Premi CIRIT per fomentar l'esperit científic del Jovent l'any 2009. El present treball és un estudi de la personalitat humana, literària i filosòfica de Jaume Brossa així com un anàlisi del medi sociohistòric que li va tocar viure. El mètode utilitzat ha estat, en primer lloc, un rastreig de material original, articles publicats entre els anys 1892 i 1902 en diversos òrgans de premsa de Barcelona i Madrid. Una vegada obtingut el material requerit, s’ha sondejat per dins de les seves línies fins a trobar quin era el seu pensament en molts aspectes, a saber: el seu posicionament entorn els grans centres d’atenció del seu temps: el nacionalisme, el moviment obrer, l’estètica modernista en les seves parcel•les de música, literatura, teatre etc., tots aquests camps, tractats des de la base de la seva actitud regeneracionista i revolucionària. L’estudi s’ha realitzat des d’un enfocament crític: intentar esbrinar quines han estat les causes per les quals un autor certament notable de les nostres lletres ha estat marginat o, si més no, minimitzat en el seu abast intel•lectual. I, tal com es planteja al començament del treball, aquest consta d’una recerca de causes, implicacions, contextos etc. que ens permetin esbrinar per què Jaume Brossa ha estat desacreditat.

Host innate immune responses to microbial pathogens.

Sepsis is among the leading causes of death worldwide and its incidence is increasing. Defined as the host response to infection, sepsis is a clinical syndrome considered to be the expression of a dysregulated immune reaction induced by danger signals that may lead to organ failure and death. Remarkable progresses have been made in our understanding of the molecular basis of host defenses in recent years. The host defense response is initiated by innate immune sensors of danger signals designated under the collective name of pattern-recognition receptors. Members of the family of microbial sensors include the complement system, the Toll-like receptors, the nucleotide-binding oligomerization domainlike receptors, the RIG-I-like helicases and the C-type lectin receptors. Ligand-activated pattern-recognition receptors kick off a cascade of intracellular events resulting in the expression of co-stimulatory molecules and release of effector molecules playing a fundamental role in the initiation of the innate and adaptive immune responses. Fine tuning of proinflammatory and anti-inflammatory reactions is critical for keeping the innate immune response in check. Overwhelming or dysregulated responses induced by infectious stimuli may have dramatic consequences for the host as shown by the profound derangements observed in sepsis. Unfortunately, translational research approaches aimed at the development of therapies targeting newly identified innate immune pathways have not held their promises. Indeed, all recent clinical investigations of adjunctive anti-sepsis treatments had little, if any, impact on morbidity and all-cause mortality of sepsis. Dissecting the mechanisms underlying the transition from infection to sepsis is essential for solving the sepsis enigma. Important components of the puzzle have already been identified, but the hunt must go on in the laboratory and at the bedside.