Coordinated regulation of follicle development by germ and somatic cells

The continuum of folliculogenesis begins in the fetal ovary with the differentiation of the oogonia and their isolation within the primordial follicles. Primordial follicle activation is an enigmatic process, whereby some follicles enter the growing pool to become primary follicles, thereby embarking on an irreversible progression towards ovulation or atresia. This process is under the coordinated regulation of factors from the oocyte itself, as well as from the somatic cells of the ovary, in particular the theca and granulosa cells, which are structural components of the follicle. These two influences provide the principal stimuli for the growth of the follicle to the late preantral or early antral stage of development. The endocrine effects of the gonadotrophins FSH and LH are essential to the continued progression of the follicle and most atresia can be attributed to the failure to receive or process the gonadotrophin signals. The peri-ovulatory state has received intensive investigation recently, demonstrating a coordinated role for gonadotrophins, steroids, epidermal growth factor family proteins and prostaglandins. Thus, a complex programme of coordinated interaction of governing elements from both germ and somatic cell sources is required for successful follicle development.

Resource entitlements of indigenous minorities, their poverty and conservation of nature: Status of Australian Aborigines, comparisons with India's tribals, theory and changing policies globally

Considers the relevance of A.K. Sen’s theory of entitlements to the situation facing indigenous tribal people, its relationship to institutionalism, and to theories of property rights. Changing world views about the resource entitlements that should be given to local communities are outlined concentrating on the views expressed by the World Conservation Union (IUCN). These changing views have relevance for the resource entitlements of indigenous tribal communities and are reflected in differences in the policy approaches inherent in the Convention on International Trade in Endangered Species (CITES) and the more recent Convention on Biological Diversity. The latter embodies the view that provision of greater resource entitlements to local communities can provide economic incentives for nature conservation. There is a case for Indigenous Australians to be given greater rights to market the natural produce from their lands. Despite progress with land rights, they are not entitled to market much of the natural produce from their land. The socioeconomic status of Australian Aborigines is outlined. Their standard of living and their life expectancy are low by world standards and in comparison to other Australians. This is partly a result of historical events that have restricted their rights. These events are outlined briefly. Views differ about the appropriate development paths for Indigenous Australians and these are assessed. Concern on environmental and economic grounds is expressed about the view that the economic development of Australian Aboriginal communities would be accelerated by replacing their communal land titles by private land titles and encouraging Western-style agriculture and commercial development of their lands. Some comparisons are also made with the situation of India’s Tribals.

Regulation of Trypanosoma cruzi-Induced Myocarditis by Programmed Death Cell Receptor

Trypanosoma cruzi infection causes intense myocarditis, leading to cardiomyopathy and severe cardiac dysfunction. Protective adaptive immunity depends on balanced signaling through a T cell receptor and coreceptors expressed on the T cell surface. Such coreceptors can trigger stimulatory or inhibitory signals after binding to their ligands in antigen-presenting cells (APC). T. cruzi modulates the expression of coreceptors in lymphocytes after infection. Deregulated inflammation may be due to unbalanced expression of these molecules. Programmed death cell receptor 1 (PD-1) is a negative T cell coreceptor that has been associated with T cell anergy or exhaustion and persistent intracellular infections. We aimed to study the role of PD-1 during T. cruzi-induced acute myocarditis in mice. Cytometry assays showed that PD-1 and its ligands are strongly upregulated in lymphocytes and APC in response to T. cruzi infection in vivo and in vitro. Lymphocytes infiltrating the myocardium exhibited high levels of expression of these molecules. An increased cardiac inflammatory response was found in mice treated with blocking antibodies against PD-1, PD-L1, and to a lesser extent, PD-L2, compared to that found in mice treated with rat IgG. Similar results in PD-1(-/-) mice were obtained. Moreover, the PD-1 blockade/deficiency led to reduced parasitemia and tissue parasitism but increased mortality. These results suggest the participation of a PD-1 signaling pathway in the control of acute myocarditis induced by T. cruzi and provide additional insight into the regulatory mechanisms in the pathogenesis of Chagas` disease.

Differential inclusions and robust control theory

Uncontrolled systems (x) over dot is an element of Ax, where A is a non-empty compact set of matrices, and controlled systems (x) over dot is an element of Ax + Bu are considered. Higher-order systems 0 is an element of Px - Du, where and are sets of differential polynomials, are also studied. It is shown that, under natural conditions commonly occurring in robust control theory, with some mild additional restrictions, asymptotic stability of differential inclusions is guaranteed. The main results are variants of small-gain theorems and the principal technique used is the Krasnosel'skii-Pokrovskii principle of absence of bounded solutions.

Should optional properties be used in conceptual modelling? A theory and three empirical tests

An important feature of some conceptual modelling grammars is the features they provide to allow database designers to show real-world things may or may not possess a particular attribute or relationship. In the entity-relationship model, for example, the fact that a thing may not possess an attribute can be represented by using a special symbol to indicate that the attribute is optional. Similarly, the fact that a thing may or may not be involved in a relationship can be represented by showing the minimum cardinality of the relationship as zero. Whether these practices should be followed, however, is a contentious issue. An alternative approach is to eliminate optional attributes and relationships from conceptual schema diagrams by using subtypes that have only mandatory attributes and relationships. In this paper, we first present a theory that led us to predict that optional attributes and relationships should be used in conceptual schema diagrams only when users of the diagrams require a surface-level understanding of the domain being represented by the diagrams. When users require a deep-level understanding, however, optional attributes and relationships should not be used because they undermine users' abilities to grasp important domain semantics. We describe three experiments which we then undertook to test our predictions. The results of the experiments support our predictions.

Blocking systemic nitric oxide production alters neuronal activation in brain structures involved in cardiovascular regulation during polymicrobial sepsis

In a previous study, we concluded that overproduction of nitric oxide (NO) by inducible nitric Oxide synthase (iNOS) in the late phase of sepsis prevents hypothalamic activation, blunts vasopressin secretion and contributes to hypotension, irreversible shock and death. The aim of this follow-up study was to evaluate if the same neuronal activation pattern happens in brain structures related to cardiovascular functions. Male Wistar rats received intraperitoneal injections of aminoguanidine, an iNOS inhibitor, or saline 30 min before cecal ligation and puncture (CLP) or sham surgeries. The animals were perfused 6 or 24 h after the surgeries and the brains were removed and processed for Fos immunocytochemistry We observed an increase (P < 0.001) in c-fos expression 6 h after CLP in the area postrema (AP), nucleus of he tractus solitarius (NTS), ventral lateral medulla (VLM), locus coeruleus (LC) and parabrachial nucleus (PB). At 24 h after CLP, however, c-fos expression was strongly decreased in all these nuclei (P < 0.05), except for the VLM. Aminoguanidine reduced c-fos expression in the AP and NTS at 6 h after CLR but showed an opposite effect at 24 h, with an increase in the AP, NTS, and also in the VLM. No such effect was observed in the LC and PB at 6 or 24 h. In all control animals, c-fos expression was minimal or absent. We conclude that in the early phase of sepsis iNOS-derived NO may be partially responsible for the activation of brain structures related to cardiovascular regulation. During the late phase, however, this activation is reduced or abolished. (C) 2009 Elsevier Ireland Ltd. All rights reserved.

Patch dynamics and metapopulation theory: the case of successional species

We present a mathematical framework that combines extinction-colonization dynamics with the dynamics of patch succession. We draw an analogy between the epidemiological categorization of individuals (infected, susceptible, latent and resistant) and the patch structure of a spatially heterogeneous landscape (occupied-suitable, empty-suitable, occupied-unsuitable and empty-unsuitable). This approach allows one to consider life-history attributes that influence persistence in patchy environments (e.g., longevity, colonization ability) in concert with extrinsic processes (e.g., disturbances, succession) that lead to spatial heterogeneity in patch suitability. It also allows the incorporation of seed banks and other dormant life forms, thus broadening patch occupancy dynamics to include sink habitats. We use the model to investigate how equilibrium patch occupancy is influenced by four critical parameters: colonization rate? extinction rate, disturbance frequency and the rate of habitat succession. This analysis leads to general predictions about how the temporal scaling of patch succession and extinction-colonization dynamics influences long-term persistence. We apply the model to herbaceous, early-successional species that inhabit open patches created by periodic disturbances. We predict the minimum disturbance frequency required far viable management of such species in the Florida scrub ecosystem. (C) 2001 Academic Press.

Up-regulation of p21(WAF1)/(CIP1) by histone deacetylase inhibitors reduces their cytotoxicity

Histone deacetylase inhibitors show promise as chemotherapeutic agents and have been demonstrated to block proliferation in a wide range of tumor cell lines. Much of this antiproliferative effect has been ascribed to the up-regulated expression of the cyclin-dependent kinase inhibitor p21(WAF1/CIP1). In this article, we report that p21 expression was up-regulated by relatively low doses of the histone deacetylase inhibitor azelaic bishydroxamic acid (ABHA) and correlated with a proliferative arrest. Higher doses of ABHA were cytotoxic. Cells that did not up-regulate p21 expression were hypersensitive to killing by ABHA and died via apoptosis, whereas up-regulation of p21 correlated with reduced sensitivity and a block in the apoptotic mechanism, and these cells seemed to die by necrosis. Using isogenic p21(+/+) and p21(-/-) cell lines and direct inhibition of caspase activity, we demonstrate that the reduced sensitivity to killing by ABHA is a consequence of inhibition of apoptosis by up-regulated p21 expression. These data indicate the enormous potential of therapeutic strategies that bypass the cytoprotective effect of p21 and act on the same molecular targets as the histone deacetylase inhibitors.

Physiological roles and regulation of mammalian sulfate transporters

All cells require inorganic sulfate for normal function. Sulfate is among the most important macronutrients; in cells and is the fourth most abundant anion in human plasma (300 muM). Sulfate is the major sulfur source in many organisms, and because it is a hydrophilic anion that cannot passively cross the lipid bilayer of cell membranes, all cells require a mechanism for sulfate influx and efflux to ensure an optimal supply of sulfate in the body. The class of proteins involved in moving sulfate into or out of cells is called sulfate transporters. To date, numerous sulfate transporters have been identified in tissues and cells from many origins. These include the renal sulfate transporters NaSi-1 and sat-1, the ubiquitously expressed diastrophic dysplasia sulfate transporter DTDST, the intestinal sulfate transporter DRA that is linked to congenital chloride diarrhea, and the erythrocyte anion exchanger AE1. These transporters have only been isolated in the last 10-15 years, and their physiological roles and contributions to body sulfate homeostasis are just now beginning to be determined. This review focuses on the structural and functional properties of mammalian sulfate transporters and highlights some of regulatory mechanisms that control their expression in vivo, under normal physiological and pathophysiological states.

A social identity theory of leadership

A social identity theory of leadership is described that views leadership as a group process generated by social categorization and prototype-based depersonalization processes associated with social identity. Group identification, as self-categorization, constructs an intragroup prototypicality gradient that invests the most prototypical member with the appearance of having influence; the appearance arises because members cognitively and behaviorally conform to the prototype. The appearance of influence becomes a reality through depersonalized social attraction processes that make followers agree and comply with the leader's ideas and suggestions. Consensual social attraction also imbues the leader with apparent status and creates a status-based structural differentiation within the group into leader(s) and followers, which has characteristics of unequal status intergroup relations. In addition, a fundamental attribution process constructs a charismatic leadership personality for the leader, which further empowers the leader and sharpens the leader-follower status differential. Empirical support for the theory is reviewed and a range of implications discussed, including intergroup dimensions, uncertainty reduction and extremism, power, and pitfalls of prototype-based leadership.