Distinctive, fine-scale distribution of Eastern Caribbean sperm whale vocal clans reflects island fidelity rather than environmental variables.

Environmental variables are often the primary drivers of species' distributions as they define their niche. However, individuals, or groups of individuals, may sometimes adopt a limited range within this larger suitable habitat as a result of social and cultural processes. This is the case for Eastern Caribbean sperm whales. While environmental variables are reasonably successful in describing the general distribution of sperm whales in the region, individuals from different cultural groups have distinct distributions around the Lesser Antilles islands. Using data collected over 2 years of dedicated surveys in the Eastern Caribbean, we conducted habitat modeling and habitat suitability analyses to investigate the mechanisms responsible for such fine-scale distribution patterns. Vocal clan-specific models were dramatically more successful at predicting distribution than general species models, showing how a failure to incorporate social factors can impede accurate predictions. Habitat variation between islands did not explain vocal clan distributions, suggesting that cultural group segregation in the Eastern Caribbean sperm whale is driven by traditions of site/island fidelity (most likely maintained through conformism and homophily) rather than habitat type specialization. Our results provide evidence for the key role of cultural knowledge in shaping habitat use of sperm whales within suitable environmental conditions and highlight the importance of cultural factors in shaping sperm whale ecology. We recommend that social and cultural information be incorporated into conservation and management as culture can segregate populations on fine spatial scales in the absence of environmental variability.

Hydrogen peroxide removes TRPM4 current desensitization conferring increased vulnerability to necrotic cell death.

Necrosis is associated with an increase in plasma membrane permeability, cell swelling, and loss of membrane integrity with subsequent release of cytoplasmic constituents. Severe redox imbalance by overproduction of reactive oxygen species is one of the main causes of necrosis. Here we demonstrate that H(2)O(2) induces a sustained activity of TRPM4, a Ca(2+)-activated, Ca(2+)-impermeant nonselective cation channel resulting in an increased vulnerability to cell death. In HEK 293 cells overexpressing TRPM4, H(2)O(2) was found to eliminate in a dose-dependent manner TRPM4 desensitization. Site-directed mutagenesis experiments revealed that the Cys(1093) residue is crucial for the H(2)O(2)-mediated loss of desensitization. In HeLa cells, which endogenously express TRPM4, H(2)O(2) elicited necrosis as well as apoptosis. H(2)O(2)-mediated necrosis but not apoptosis was abolished by replacement of external Na(+) ions with sucrose or the non-permeant cation N-methyl-d-glucamine and by knocking down TRPM4 with a shRNA directed against TRPM4. Conversely, transient overexpression of TRPM4 in HeLa cells in which TRPM4 was previously silenced re-established vulnerability to H(2)O(2)-induced necrotic cell death. In addition, HeLa cells exposed to H(2)O(2) displayed an irreversible loss of membrane potential, which was prevented by TRPM4 knockdown.

P2X4 activation modulates volume-sensitive outwardly rectifying chloride channels in rat hepatoma cells.

Volume-sensitive outwardly rectifying (VSOR) Cl(-) channels are critical for the regulatory volume decrease (RVD) response triggered upon cell swelling. Recent evidence indicates that H(2)O(2) plays an essential role in the activation of these channels and that H(2)O(2) per se activates the channels under isotonic isovolumic conditions. However, a significant difference in the time course for current onset between H(2)O(2)-induced and hypotonicity-mediated VSOR Cl(-) activation is observed. In several cell types, cell swelling induced by hypotonic challenges triggers the release of ATP to the extracellular medium, which in turn, activates purinergic receptors and modulates cell volume regulation. In this study, we have addressed the effect of purinergic receptor activation on H(2)O(2)-induced and hypotonicity-mediated VSOR Cl(-) current activation. Here we show that rat hepatoma cells (HTC) exposed to a 33% hypotonic solution responded by rapidly activating VSOR Cl(-) current and releasing ATP to the extracellular medium. In contrast, cells exposed to 200 microm H(2)O(2) VSOR Cl(-) current onset was significantly slower, and ATP release was not detected. In cells exposed to either 11% hypotonicity or 200 microm H(2)O(2), exogenous addition of ATP in the presence of extracellular Ca(2+) resulted in a decrease in the half-time for VSOR Cl(-) current onset. Conversely, in cells that overexpress a dominant-negative mutant of the ionotropic receptor P2X4 challenged with a 33% hypotonic solution, the half-time for VSOR Cl(-) current onset was significantly slowed down. Our results indicate that, at high hypotonic imbalances, swelling-induced ATP release activates the purinergic receptor P2X4, which in turn modulates the time course of VSOR Cl(-) current onset in a extracellular Ca(2+)-dependent manner.

[The system of informal caregiving as inequality]. / El sistema informal de cuidados en clave de desigualdad.

In our setting, it is families, not the health and social services, who play the greatest role in providing continuous care to persons in need of such services. Informal health care poses two key questions with regard to the issue of equity: differences in the burdens borne by men and women, which contribute to gender inequality and, depending on their educational and socio-economic level, inequities in their ability to choose and gain access to needed resources and support services, thus contributing to social class inequalities. Distributing the burden of caregiving between men and women, and between the family and the state, constitutes a crucial debate in public health. This study analyzes the concept and characteristics of informal care, provides data on its dimensions in our setting, and analyzes the profile of caregivers, as well as the work they do and the impact it has on their lives. Finally, it presents currently existing models and support strategies for informal caregivers. It is largely women who assume the principal role of providing informal care, undertaking the most difficult and demanding tasks and dedicating the largest share of their time to them. As a result, women bear an elevated cost in their lives in terms of health, quality of life, access to employment and professional development, social relations, availability of time for themselves, and economic repercussions. Unemployed, under-educated women from the least privileged social classes constitute the largest group of informal caregivers in our country. Any policies aimed at supporting those who provide such care should keep in mind the unequal point from which they start and be evaluated in terms of their impact on gender and social class inequality.

Hydroxyl radical activation of a Ca(2+)-sensitive nonselective cation channel involved in epithelial cell necrosis.

In a previous work the involvement of a fenamate-sensitive Ca(2+)-activated nonselective cation channel (NSCC) in free radical-induced rat liver cell necrosis was demonstrated (5). Therefore, we studied the effect of radical oxygen species and oxidizing agents on the gating behavior of a NSCC in a liver-derived epithelial cell line (HTC). Single-channel currents were recorded in HTC cells by the excised inside-out configuration of the patch-clamp technique. In this cell line, we characterize a 19-pS Ca(2+)-activated, ATP- and fenamate-sensitive NSCC nearly equally permeable to monovalent cations. In the presence of Fe(2+), exposure of the intracellular side of NSCC to H(2)O(2) increased their open probability (P(o)) by approximately 40% without affecting the unitary conductance. Desferrioxamine as well as the hydroxyl radical (.OH) scavenger MCI-186 inhibited the effect of H(2)O(2), indicating that the increase in P(o) was mediated by.OH. Exposure of the patch membrane to the oxidizing agent 5,5'-dithio-bis-2-nitrobenzoic acid (DTNB) had a similar effect to.OH. The increase in P(o) induced by.OH or DTNB was not reverted by preventing formation or by DTNB washout, respectively. However, the reducing agent dithiothreitol completely reversed the effects on P(o) of both.OH and DTNB. A similar increase in P(o) was observed by applying the physiological oxidizing molecule GSSG. Moreover, GSSG-oxidized channels showed enhanced sensitivity to Ca(2+). The effect of GSSG was fully reversed by GSH. These results suggest an intracellular site(s) of action of oxidizing agents on cysteine targets on the fenamate-sensitive NSCC protein implicated in epithelial cell necrosis.

Non-selective cation channels and oxidative stress-induced cell swelling.

Necrosis is considered as a non-specific form of cell death that induces tissue inflammation and is preceded by cell swelling. This increase in cell volume has been ascribed mainly to defective outward pumping of Na+ caused by metabolic depletion and/or to increased Na+ influx via membrane transporters. A specific mechanism of swelling and necrosis driven by the influx of Na+ through nonselective cation channels has been recently proposed (Barros et al., 2001a). We have characterized further the properties of the nonselective cation channel (NSCC) in HTC cells. The NSCC shows a conductance of approximately 18 pS, is equally permeable to Na+ and K+, impermeant to Ca2+, requires high intracellular Ca2+ as well as low intracellular ATP for activation and is inhibited by flufenamic acid. Hydrogen peroxide induced a significant increase in cell volume that was dependent on external Na+. We propose that the NSCC, which is ubiquitous though largely inactive in healthy cells, becomes activated under severe oxidative stress. The ensuing Na+ influx initiates via positive feedback a series of metabolic and electrolytic disturbances, resulting in cell death by necrosis.

El sistema informal de cuidados en clave de desigualdad / The system of informal caregiving as inequality

Los servicios sociales y sanitarios participan de forma minoritaria en el cuidado continuado de las personas que lo necesitan, y la familia constituye la principal prestadora de cuidados en nuestro entorno. La atención informal a la salud plantea dos cuestiones relacionadas con la equidad: las cargas diferenciales del cuidado entre hombres y mujeres, que generan una desigualdad de género, y la inequidad en capacidad de elección y de acceso a recursos y servicios de ayuda según el nivel educativo y socioeconómico, que plantea una desigualdad de clase social. La distribución de la responsabilidad de cuidar entre hombres y mujeres y entre familia y estado constituye un debate crucial de la salud pública. En este trabajo se analiza el concepto y características del cuidado informal, se aportan datos sobre su magnitud en nuestro medio y se analiza el perfil de las personas cuidadoras, el trabajo que realizan y el impacto que supone en sus vidas. Finalmente, se plantean modelos y estrategias de apoyo a cuidadores/as existentes en la actualidad. Las mujeres asumen de forma mayoritaria el papel de cuidadoras principales, se responsabilizan de las tareas más pesadas y demandantes y dedican más tiempo a cuidar. El coste que asumen las mujeres en sus vidas por el hecho de ser cuidadoras es elevado en términos de salud, calidad de vida, acceso al empleo y desarrollo profesional, relaciones sociales, disponibilidad del propio tiempo y repercusiones económicas. Las mujeres de menor nivel educativo, sin empleo y de clases sociales menos privilegiadas configuran el gran colectivo de cuidadoras en nuestro país. Cualquier política de apoyo a cuidadores debería tener en cuenta esta desigual situación de partida y ser evaluada en términos de su impacto en desigualdad de género y clase social (AU)

Non-selective cation channels and oxidative stress-induced cell swelling

Necrosis is considered as a non-specific form of cell death that induces tissue inflammation and is preceded by cell swelling. This increase in cell volume has been ascribed mainly to defective outward pumping of Na+ caused by metabolic depletion and/or to increased Na+ influx via membrane transporters. A specific mechanism of swelling and necrosis driven by the influx of Na+ through nonselective cation channels has been recently proposed (Barros et al., 2001a). We have characterized further the properties of the nonselective cation channel (NSCC) in HTC cells. The NSCC shows a conductance of approximately 18 pS, is equally permeable to Na+ and K+, impermeant to Ca2+, requires high intracellular Ca2+ as well as low intracellular ATP for activation and is inhibited by flufenamic acid. Hydrogen peroxide induced a significant increase in cell volume that was dependent on external Na+. We propose that the NSCC, which is ubiquitous though largely inactive in healthy cells, becomes activated under severe oxidative stress. The ensuing Na+ influx initiates via positive feedback a series of metabolic and electrolytic disturbances, resulting in cell death by necrosis