Blockade of ovulation after atropine implants in the lateral hypothalamus of the rat

Résumé Des implantations d'atropine dans l'hypothalamus antérieur et latéral de la rate provoquent un diestrus prolongé et une diminution du poids de l'ovaire sans réponse utérine au déciduome traumatique. On conclut que l'atropine agit sur des voies colinérgiques en relation avec la sécrétion des gonadotrophines.

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This work was presented in part at the Third Latin American Meeting on Research in Human Reproduction (ALIRH) 1968 (Salvador, Bahia, Brasil).     

Identification and characterization of new functional truncated variants of somatostatin receptor subtype 5 in rodents

Somatostatin and cortistatin exert multiple biological actions through five receptors (sst1-5); however, not all their effects can be explained by activation of sst1-5. Indeed, we recently identified novel truncated but functional human sst5-variants, present in normal and tumoral tissues. In this study, we identified and characterized three novel truncated sst5 variants in mice and one in rats displaying different numbers of transmembrane-domains [TMD; sst5TMD4, sst5TMD2, sst5TMD1 (mouse-variants) and sst5TMD1 (rat-variant)]. These sst5 variants: (1) are functional to mediate ligand-selective-induced variations in [Ca²⁺]_i and cAMP despite being truncated; (2) display preferential intracellular distribution; (3) mostly share full-length sst5 tissue distribution, but exhibit unique differences; (4) are differentially regulated by changes in hormonal/metabolic environment in a tissue- (e.g., central vs. systemic) and ligand-dependent manner. Altogether, our results demonstrate the existence of new truncated sst5-variants with unique ligand-selective signaling properties, which could contribute to further understanding the complex, distinct pathophysiological roles of somatostatin and cortistatin.     

Simvastatin overcomes the resistance to serum withdrawal-induced apoptosis of lymphocytes from Alzheimer’s disease patients

Statins may exert beneficial effects on Alzheimer’s disease (AD) patients. Based on the antineoplastic and apoptotic effects of statins in a number of cell types, we hypothesized that statins may be able to protect neurons by controlling the regulation of cell cycle and/or apoptosis. A growing body of evidence indicates that neurodegeneration involves the cell-cycle activation in postmitotic neurons. Failure of cell-cycle control is not restricted to neurons in AD patients, but occurs in peripheral cells as well. For these reasons, we studied the role of simvastatin (SIM) on cell survival/death in lymphoblasts from AD patients. We report here that SIM induces apoptosis in AD lymphoblasts deprived of serum. SIM interacts with PI3K/Akt and ERK1/2 signaling pathways thereby decreasing the serum withdrawal-enhanced levels of the CDK inhibitor p21^Cip1 (p21) and restoring the vulnerability of AD cells to trophic factor deprivation.     

IgE-binding trypsin inhibitors in plant pollen extracts

In an attempt to access the possible role of protease-antiprotease mechanisms of non-immune defence in pollinosis, only low levels of trypsin-, kallikrein- or plasmin-like proteinases could be detected in aqueous pollen extracts. In contrast, several pollen species displayed appreciable trypsin inhibitory activity, e.g.Parietaria, Olea, Ambrosia, Rumex, Chenopodium, Holcus andPoa spp. These proteins of the serpin family of anti-proteinases were found to bind specific IgE-antibodies from the serum of hay fever patients. As examples, the IgE-binding trypsin inhibitors from the pollen ofParietaria judaica andAmbrosia elatior were purified and characterized as acidic proteins with pI 4.2 and a molecular weight of 20–24 kDa.     

Hydroxylation of demethoxy-Q6 constitutes a control point in yeast coenzyme Q6 biosynthesis

Coenzyme Q is a lipid molecule required for respiration and antioxidant protection. Q biosynthesis in Saccharomyces cerevisiae requires nine proteins (Coq1p–Coq9p). We demonstrate in this study that Q levels are modulated during growth by its conversion from demethoxy-Q (DMQ), a late intermediate. Similar conversion was produced when cells were subjected to oxidative stress conditions. Changes in Q₆/DMQ₆ ratio were accompanied by changes in COQ7 gene mRNA levels encoding the protein responsible for the DMQ hydroxylation, the penultimate step in Q biosynthesis pathway. Yeast coq null mutant failed to accumulate any Q late biosynthetic intermediate. However, in coq7 mutants the addition of exogenous Q produces the DMQ synthesis. Similar effect was produced by over-expressing ABC1/COQ8. These results support the existence of a biosynthetic complex that allows the DMQ₆ accumulation and suggest that Coq7p is a control point for the Q biosynthesis regulation in yeast. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users. Received 04 September 2008; received after revision 22 October 2008; accepted 23 October 2008     

French historical epistemology: Discourse,concepts, and the norms of rationality

In recent years, analytic philosophers have begun to recognize the value of the French school of historical epistemology (as embodied by figures such as Jean Cavaillès, Gaston Bachelard, Georges Canguilhem, and Michel Foucault) for contemporary debates in the history and philosophy of science. This tradition, which some characterize as a ‘French’ approach to the philosophy of science, however, remains largely un-read by mainstream philosophers of science. This article offers an interpretation of this tradition, highlighting what the author takes to be its two central features: (i) its claim that scientific discourse is the object of epistemology and (ii) its claim that scientific concepts are the building blocks of scientific discourse.     

Mutations in the gene encoding the latency-associated peptide of TGF-beta 1 cause Camurati-Engelmann disease

Camurati-Engelmann disease (CED; MIM 131300), or progressive diaphyseal dysplasia, is a rare, sclerosing bone dysplasia inherited in an autosomal dominant manner. Recently, the gene causing CED has been assigned to the chromosomal region 19q13 (refs 1-3). Because this region contains the gene encoding transforming growth factor-beta 1 (TGFB1), an important mediator of bone remodelling, we evaluated TGFB1 as a candidate gene for causing CED.     

Comparative analysis of the genome sequences of Bordetella pertussis,Bordetella parapertussis and Bordetella bronchiseptica

Bordetella pertussis, Bordetella parapertussis and Bordetella bronchiseptica are closely related Gram-negative beta-proteobacteria that colonize the respiratory tracts of mammals. B. pertussis is a strict human pathogen of recent evolutionary origin and is the primary etiologic agent of whooping cough. B. parapertussis can also cause whooping cough, and B. bronchiseptica causes chronic respiratory infections in a wide range of animals. We sequenced the genomes of B. bronchiseptica RB50 (5,338,400 bp; 5,007 predicted genes), B. parapertussis 12822 (4,773,551 bp; 4,404 genes) and B. pertussis Tohama I (4,086,186 bp; 3,816 genes). Our analysis indicates that B. parapertussis and B. pertussis are independent derivatives of B. bronchiseptica-like ancestors. During the evolution of these two host-restricted species there was large-scale gene loss and inactivation; host adaptation seems to be a consequence of loss, not gain, of function, and differences in virulence may be related to loss of regulatory or control functions.     

Cultural-Biology: Systemic Consequences of <Emphasis Type="Italic">Our</Emphasis> Evolutionary Natural Drift as Molecular Autopoietic Systems

Our purpose in this essay is to introduce new concepts (dynamic architecture and dynamic ecological organism-niche unity, among other) in a wide and recursive view of the systemic consequences of the following biological facts that I (Maturana in Biology of cognition, 1970, Unity and diversity of man. Le Seuil, Paris, 1978; Maturana and Varela in Autopoiesis and cognition: the realization of the living. D. Riedel Publishing Co, Boston, 1980, El Árbol del Conocimiento: Las Bases Biológicas del Conocer Humano, 1a Edición. Editorial Universitaria, Santiago, 1984; Maturana and Mpodozis in Rev Chil Hist Nat 73:261–310, 2000) and we (Maturana and Dávila in Habitar humano: en seis ensayos de biología-cultural. Juan Carlos Sáez Editorial, Chile, 2008) have presented that can be resumed as: (1) that as living systems we human beings are molecular autopoietic system; (2) that living systems live only as long as they find themselves in a medium that provides them with all the conditions that make the realization of their living possible, that is, in the continuous conservation of their relation of adaptation to the circumstances in which they find themselves; (3) that as a living system exists only in a relation of adaptation with the medium that operates as its ecological niche, its reproduction necessarily occurs as a process of systemic duplication or multiplication of the ecological organism-niche unity that it integrates; (4) that the worlds of doings that we generate as languaging beings in our conversations, explanations, reflections and theories are part of our ecological niche; and (5) that we human beings as living beings that exist in languaging, are biological–cultural beings in which our cultural and our biological manners of existences can be distinguished but cannot be separated. Of the systemic consequences of these biological facts that we consider in this essay, we wish to mention two as the principal: (1) that the diversification of manners of living produced in biological evolution is the result of differential survival in a changing medium through the conservation of adaptation, and not through competitive survival of the best; and (2) that we in our living as languaging human beings (observers) are the epistemological fundament of all that we do and know as such.     

Similarity between the effects of suprachiasmatic nuclei lesions and of pinealectomy on gonadotropin release in ovariectomized,sulpiride-treated and melatonin-replaced rats

The aim of this study was to compare the effects of pineal indole treatments on LH and FSH release in pinealectomized and suprachiasmatic lesioned and ovariectomized rats rendered hyperprolactinemic by acute sulpiride treatment. pinealectomy or suprachiasmatic nuclei lesions in female rats both decreased plasma LH and FHS at 10, but not at 20 d after surgery, whereas the daily afternoon administration of melatonin effectively restored levels of both gonadotropins to control values. In ovariectomized rats, pinealectomy or suprachiasmatic nuclei lesions were ineffective in counteracting the high plasma levels of LH and FSH. However, sulpiride treatment in both pinealectomized and suprachiasmatic nuclei lesioned and castrated female rats significantly decreased the levels of LH and FSH, an effect which was counteracted by daily afternoon melatonin administration. Other pineal indoles tested, i.e., 5-hydroxy- and 5-methoxytryptophol, were ineffective in regulating gonadotropin levels. The results suggest that the pineal gland, through its hormone melatonin, can modulate gonadotropin secretion by acting on a dopamine mechanism independent of hypothalamic suprachiasmatic areas.