Recognizing animal personhood in compassionate conservation.

Compassionate conservation is based on the ethical position that actions taken to protect biodiversity should be guided by compassion for all sentient beings. Critics argue that there are 3 core reasons harming animals is acceptable in conservation programs: the primary purpose of conservation is biodiversity protection; conservation is already compassionate to animals; and conservation should prioritize compassion to humans. We used argument analysis to clarify the values and logics underlying the debate around compassionate conservation. We found that objections to compassionate conservation are expressions of human exceptionalism, the view that humans are of a categorically separate and higher moral status than all other species. In contrast, compassionate conservationists believe that conservation should expand its moral community by recognizing all sentient beings as persons. Personhood, in an ethical sense, implies the individual is owed respect and should not be treated merely as a means to other ends. On scientific and ethical grounds, there are good reasons to extend personhood to sentient animals, particularly in conservation. The moral exclusion or subordination of members of other species legitimates the ongoing manipulation and exploitation of the living worlds, the very reason conservation was needed in the first place. Embracing compassion can help dismantle human exceptionalism, recognize nonhuman personhood, and navigate a more expansive moral space.

Reconocimiento de la Calidad de Persona en los Animales dentro de la Conservación Compasiva Resumen La conservación compasiva está basada en la posición ética que parte de que las acciones tomadas para proteger a la biodiversidad deberían estar dirigidas por la compasión por todos los seres sintientes. Los críticos de esta postura argumentan que hay tres razones nucleares por las que el daño a los animales es aceptable dentro de los programas de conservación: el principal motivo de la conservación es la protección de la biodiversidad; la conservación ya es compasiva con los animales; y la conservación debería priorizar la compasión hacia los humanos. Usamos un análisis de argumentos para aclarar los valores y la lógica subyacentes al debate en torno a la conservación compasiva. Encontramos que el rechazo a la conservación compasiva es una expresión de la excepcionalidad humana, la visión de que los humanos están en un nivel categóricamente separado y de mayor moral que todas las demás especies. Por el contrario, los conservacionistas compasivos creen que la conservación debería expandir su comunidad moral al reconocer a todos los seres sintientes como personas. La calidad de persona, en un sentido ético, implica que el individuo merece respeto y no debería ser tratado solamente como un medio para otros fines. Si hablamos desde fundamentos científicos y éticos, existen muy buenas razones para extender la calidad de persona a todos los animales sintientes, particularmente en la conservación. La exclusión moral o la subordinación de los miembros de otras especies justifica la continua manipulación y explotación de los seres vivos, la justa razón por la que necesitamos de la conservación desde el principio. La aceptación de la compasión nos puede ayudar a desmantelar la excepcionalidad humana, a reconocer la calidad de persona no humana y a navegar un espacio moral más expansivo.

A moral panic over cats.

Some conservationists believe that free-ranging cats pose an enormous risk to biodiversity and public health and therefore should be eliminated from the landscape by any means necessary. They further claim that those who question the science or ethics behind their arguments are science deniers (merchants of doubt) seeking to mislead the public. As much as we share a commitment to conservation of biodiversity and wild nature, we believe these ideas are wrong and fuel an unwarranted moral panic over cats. Those who question the ecological or epidemiological status of cats are not science deniers, and it is a false analogy to compare them with corporate and right-wing special interests that perpetrate disinformation campaigns over issues, such as smoking and climate change. There are good conservation and public-health reasons and evidence to be skeptical that free-ranging cats constitute a disaster for biodiversity and human health in all circumstances. Further, there are significant and largely unaddressed ethical and policy issues (e.g., the ethics and efficacy of lethal management) relative to how people ought to value and coexist with cats and native wildlife. Society is better served by a collaborative approach to produce better scientific and ethical knowledge about free-ranging cats.

Pánico Moral por los Gatos Resumen Algunos conservacionistas creen que los gatos sueltos representan un riesgo enorme para la biodiversidad y la salud pública, por lo que deberían ser eliminados del paisaje a como dé lugar. Los conservacionistas además alegan que quienes cuestionan la ciencia o la ética detrás de estos argumentos son negadores de la ciencia (mercaderes de la duda) que buscan desinformar al público. Por mucho que compartamos un compromiso con la conservación de la biodiversidad y la fauna silvestre, creemos que estás ideas están equivocadas y alimentan un pánico moral injustificado por los gatos. Aquellos que cuestionan el estado ecológico o epidemiológico de los gatos no son negadores de la ciencia y es una analogía falsa compararlos con los intereses especiales de los corporativos y de la derecha política, los cuales perpetúan las campañas de desinformación de temas como el cigarro y el cambio climático. Existen razones y evidencias de conservación y salud pública para ser escépticos sobre el argumento de que los gatos sueltos constituyen un desastre para la biodiversidad y la salud humana bajo todas las circunstancias. Además, hay temas éticos y políticos que no reciben atención (p. ej.: la ética y la eficacia del manejo letal) relativos a cómo las personas deberían valorar y coexistir con los gatos y la fauna nativa. La sociedad se beneficia más con una estrategia colaborativa para producir un mejor conocimiento científico y ético sobre los gatos que viven sueltos.

Author Correction: Intergenerational equity can help to prevent climate change and extinction.

The original Article mistakenly coded the constitutional rights of Australia as containing a governmental duty to protect the environment (blue in the figures); this has been corrected to containing no explicit mention of environmental protection (orange in the figures). The original Article also neglected to code the constitutional rights of the Cayman Islands (no data; yellow in the figures); this has been corrected to containing a governmental duty to protect the environment (blue in the figures).Although no inferences changed as a result of these errors, many values changed slightly and have been corrected. The proportion of the world's nations having constitutional rights to a healthy environment changed from 75% to 74%. The proportions of nations in different categories given in the Fig. 1 caption all changed except purple countries (3.1%): green countries changed from 47.2% to 46.9%; blue countries changed from 24.4% to 24.2%; and orange countries changed from 25.3% to 25.8%. The proportion of the global atmospheric CO2 emitted by the 144 nations changed from 72.6% to 74.4%; the proportion of the world's population represented by the 144 nations changed from 84.9% to 85%. The values of annual average CO2 emissions for blue countries changed from 363,000 Gg to 353,000 Gg and for orange countries from 195,000 Gg to 201,000 Gg. The proportion of threatened mammals endemic to a single country represented by the 144 countries changed from 91% to 84%. Figures 1-3 have been updated to show the correct values and map colours and the Supplementary Information has been updated to give the correct country codes.

Endoplasmic reticulum stress and unfolded protein response in Atm-deficient thymocytes and thymic lymphoma cells are attributable to oxidative stress.

Both oxidative stress and endoplasmic reticulum (ER) stress have been implicated in carcinogenesis. It is well documented that cells deficient in the ataxia-telangiectasia mutated (ATM) gene undergo oxidative stress, which is critically involved in thymic lymphomagenesis in Atm-/- mice. Here we demonstrate that undifferentiated Atm-/- thymocytes show signs of ER stress and of the unfolded protein response (UPR). Using two-dimensional (2-D) gel electrophoresis and mass spectrometry (MS) analysis, we identified 22 differentially expressed proteins, including the ER stress marker glucose-regulated protein 78 (GRP78), in Atm-/- thymocytes and in Atm-/- thymic lymphoma cells relative to Atm+/+ thymocytes. The phosphorylated alpha subunit of eukaryotic translation initiation factor 2 (p-eIF2alpha), a UPR marker, was also increased in Atm-/- thymocytes. Cells of the ATL-1 line, which were derived from an Atm-/- mouse thymic lymphoma, were more sensitive to the ER stress inducer tunicamycin than were Atm+/+ thymic leukemia ASL-1 cells. Notably, treatment with hydrogen peroxide duplicated the effects of ATM deficiency in cultured thymocytes, and treatment with the novel cell-permeable thiol antioxidant N-acetylcysteine amide (AD4) reduced elevated p-eIF2alpha levels in thymocytes of Atm-/- mice. Thus, we propose that ER stress and the UPR are secondary to oxidative stress in Atm-/- thymocytes.

The glucocorticoid receptor is increased in Atm-/- thymocytes and in Atm-/- thymic lymphoma cells, and its nuclear translocation counteracts c-myc expression.

We have previously demonstrated that spontaneous DNA synthesis in immature thymocytes of Atm-/- mice is elevated, and that treatment with the glucocorticoid dexamethasone (Dex) attenuates this increased DNA synthesis and prevents the development of thymic lymphomas. Deregulation of c-myc may drive the uncontrolled proliferation of Atm-/- thymocytes, since upregulation of c-myc parallels the elevated DNA synthesis in the cells. In this study, we show that the glucocorticoid receptor (GR) is expressed at high levels in Atm-/- thymocytes and in Atm-/- thymic lymphoma cells, although serum glucocorticoid (GC) levels in Atm-/- mice are similar to those in Atm+/+ mice. In cultured Atm-/- thymic lymphoma cells treated with Dex, GR nuclear translocation occurs, resulting in suppression of DNA synthesis and c-myc expression at both the mRNA and protein levels. Interestingly, the GR antagonist RU486 also causes GR nuclear translocation, but does not affect DNA synthesis and c-myc expression in Atm-/- thymic lymphoma cells. As expected, RU486 reverses the suppressive effects of Dex on DNA synthesis and c-myc expression. Administration of Dex to Atm-/- mice decreases the elevated c-Myc protein levels in their thymocytes. These findings suggest that GC/GR signaling plays an important role in regulating c-myc expression in Atm-/- thymocytes and thymic lymphoma cells.

ATM controls c-Myc and DNA synthesis during postnatal thymocyte development through regulation of redox state.

The oncoprotein c-Myc is essential for thymocyte development, and its dysregulation causes lymphoid malignancies. We have demonstrated previously that spontaneous DNA synthesis in Atm(-/-) thymocytes is markedly increased over that of Atm(+/+) thymocytes and that glucocorticoid dexamethasone suppresses thymocyte DNA synthesis and prevents the ultimate development of thymic lymphoma in Atm(-/-) mice. Recently, we reported that in Atm(-/-) thymic lymphoma cells c-Myc is overexpressed compared with the levels of c-Myc in primary thymocytes from wild-type or Atm(-/-) mice. In this study, we show that c-Myc expression progressively increases with age in primary thymocytes from Atm(-/-) mice and that the upregulation of c-Myc parallels the elevated DNA synthesis in the cells, suggesting that deregulation of c-Myc may drive the uncontrolled proliferation of thymocytes in Atm(-/-) mice. Here we also demonstrate that Atm(-/-) thymocytes exhibit increased levels of hydrogen peroxide, NF-E2-related factor (Nrf-2), peroxiredoxin-1, and intracellular glutathione relative to thymocytes from Atm(+/+) mice. Importantly, reduction of hydrogen peroxide by administration of the antioxidant N-acetylcysteine to Atm(-/-) mice attenuates the elevation of Nrf-2, c-Myc, and DNA synthesis in their thymocytes, suggesting that ATM may control c-Myc and DNA synthesis during postnatal thymocyte development by preventing accumulation of reactive oxygen species.

Retrovirus-induced oxidative stress with neuroimmunodegeneration is suppressed by antioxidant treatment with a refined monosodium alpha-luminol (Galavit).

Oxidative stress is involved in many human neuroimmunodegenerative diseases, including human immunodeficiency virus disease/AIDS. The retrovirus ts1, a mutant of Moloney murine leukemia virus, causes oxidative stress and progressive neuro- and immunopathology in mice infected soon after birth. These pathological changes include spongiform neurodegeneration, astrogliosis, thymic atrophy, and T-cell depletion. Astrocytes and thymocytes are directly infected and killed by ts1. Neurons are not infected, but they also die, most likely as an indirect result of local glial infection. Cytopathic effects of ts1 infection in cultured astrocytes are associated with accumulation of the viral envelope precursor protein gPr80env in the endoplasmic reticulum (ER), which triggers ER stress and oxidative stress. We have reported (i) that activation of the Nrf2 transcription factor and upregulation of antioxidative defenses occurs in astrocytes infected with ts1 in vitro and (ii) that some ts1-infected astrocytes survive infection by mobilization of these pathways. Here, we show that treatment with a refined monosodium alpha-luminol (Galavit; GVT) suppresses oxidative stress and Nrf2 activation in cultured ts1-infected astrocytes. GVT treatment also inhibits the development of spongiform encephalopathy and gliosis in the central nervous system (CNS) in ts1-infected mice, preserves normal cytoarchitecture in the thymus, and delays paralysis, thymic atrophy, wasting, and death. GVT treatment of infected mice reduces ts1-induced oxidative stress, cell death, and pathogenesis in both the CNS and thymus of treated animals. These studies suggest that oxidative stress mediates ts1-induced neurodegeneration and T-cell loss.

Astrocytes survive chronic infection and cytopathic effects of the ts1 mutant of the retrovirus Moloney murine leukemia virus by upregulation of antioxidant defenses.

The ts1 mutant of Moloney murine leukemia virus (MoMuLV) induces a neurodegenerative disease in mice, in which glial cells are infected by the retrovirus but neurons are not. ts1 infection of primary astrocytes, or of the immortalized astrocytic cell line C1, results in accumulation of the ts1 gPr80(env) envelope protein in the endoplasmic reticulum (ER), with ER and oxidative stress. Notably, only about half of the infected astrocytes die in these cultures, while the other half survive, continue to proliferate, and continue to produce virus. To determine how these astrocytes survive ts1 infection in culture, we established a chronically infected subline of the living cells remaining after the death of all acutely infected cells in an infected C1 cell culture (C1-ts1-S). We report here that C1-ts1-S cells proliferate more slowly, produce less virus, show reduced H2O2 levels, increase their uptake of cystine, and maintain higher levels of intracellular GSH and cysteine compared to acutely infected or uninfected C1 cells. C1-ts1-S cells also upregulate their thiol antioxidant defenses by activation of the transcription factor NF-E2-related factor 2 (Nrf2) and its target genes. Interestingly, despite maintenance of higher levels of intracellular reduced thiols, C1-ts1-S cells are more sensitive to cystine deprivation than uninfected C1 cells. We conclude that some ts1-infected astrocytes survive and adapt to virus-induced oxidative stress by successfully mobilizing their thiol redox defenses.

ATM deficiency induces oxidative stress and endoplasmic reticulum stress in astrocytes.

ATM kinase, the product of the ataxia telangiectasia mutated (Atm) gene, is activated by genomic damage. ATM plays a crucial role in cell growth and development. Here we report that primary astrocytes isolated from ATM-deficient mice grow slowly, become senescent, and die in culture. However, before reaching senescence, these primary Atm(-/-) astrocytes, like Atm(-/-) lymphocytes, show increased spontaneous DNA synthesis. These astrocytes also show markers of oxidative stress and endoplasmic reticulum (ER) stress, including increased levels of heat shock proteins (HSP70 and GRP78), malondialdehyde adducts, Cu/Zn superoxide dismutase, procaspase 12 cleavage, and redox-sensitive phosphorylation of extracellular signal-regulated protein kinase 1 and 2 (ERK1/2). In addition, HSP70 and ERK1/2 phosphorylation are upregulated in the cerebella of ATM-deficient mice. This increase in ERK1/2 phosphorylation is seen primarily in cerebellar astrocytes, or Bergmann glia, near degenerating Purkinje cells. ERK1/2 activation and astrogliosis are also found in other parts of the brain, for example, the cortex. We conclude that ATM deficiency induces intrinsic growth defects, oxidative stress, ER stress, and ERKs activation in astrocytes.

Activation of transcription factor Nrf-2 and its downstream targets in response to moloney murine leukemia virus ts1-induced thiol depletion and oxidative stress in astrocytes.

The neuroimmunodegenerative syndrome that develops in mice infected with ts1, a mutant of Moloney murine leukemia virus, resembles human AIDS. Both ts1 and human immunodeficiency virus type 1 infect astrocytes, microglia, and oligodendrocytes but do not infect neurons. Oxidative stress has been implicated in the neuropathology of AIDS dementia and other neurodegenerative diseases. We report here that ts1 infection of astrocytes (both transformed C1 cells and primary cultures) also induces thiol (i.e., glutathione and cysteine) depletion and reactive oxygen species (ROS) accumulation, events occurring in parallel with viral envelope precursor gPr80(env) accumulation and upregulated expression of endoplasmic reticulum chaperones GRP78 and GRP94. Furthermore, ts1-infected astrocytes mobilize their thiol redox defenses by upregulating levels of the Nrf-2 transcription factor, as well its targets, the xCT cystine/glutamate antiporter, gamma-glutamylcysteine ligase, and glutathione peroxidase. Depleting intracellular thiols by treating uninfected astrocytes with buthionine sulfoximine (BSO), a glutathione synthesis inhibitor, or by culturing in cystine-deficient medium, also induces ROS accumulation, activates Nrf-2, and upregulates Nrf-2 target gene expression in these astrocytes. Overexpression of Nrf-2 in astrocytes specifically increases expression of the above thiol synthesis-related proteins. Further treatment with BSO or N-acetylcysteine in transfected cells modulates this expression. Thiol depletion also accelerates cell death, while thiol supplementation promotes survival of ts1-infected cells. Together, our results indicate that ts1 infection of astrocytes, along with ts1-induced gPr80(env) accumulation, endoplasmic reticulum stress, thiol depletion, and oxidative stress, accelerates cell death; in response to the thiol depletion and oxidative stress, astrocytes activate their Nrf-2-mediated thiol antioxidant defenses, promoting cell survival.

Prevention of thymic lymphoma development in Atm-/- mice by dexamethasone.

We have reported (M. Yan et al., FASEB J., 15: 1132-1138, 2001) that spontaneous DNA synthesisis markedly increased in the thymocytes from the atrophied thymi of young Atm-/- mice. We, therefore, set out to determine whether this elevated DNA synthesis is responsible for the development of thymic lymphomas in all Atm-/- mice by 4-5 months of age. We show here that in Atm-/- mice: (a) increased DNA synthesis occurs, especially in the immature CD4(-) CD8(-) (dominant negative) and CD8(+) thymocyte populations; (b) the relative percentage of dominant negative cells increases significantly during postnatal development, with a sharp peak at 4 weeks of age; and (c) dexamethasone suppresses DNA synthesis in these thymocytes and prevents thymic lymphoma development. These observations suggest that ataxia telangiectasia mutated (ATM) down-regulates the proliferation of thymocytes, allowing T-cell development and differentiation. The results also show that dexamethasone, like ATM, checks DNA synthesis in developing thymocytes. Finally, the data document for the first time that dexamethasone prevents or slows thymic lymphoma development in Atm-/- mice.

The peroxisome proliferator phenylbutyric acid (PBA) protects astrocytes from ts1 MoMuLV-induced oxidative cell death.

Oxidative stress is involved in the pathogenesis of several neurodegenerative diseases, including Parkinson's disease, Alzheimer's disease, and HIV neuroAIDS. In this study, we have investigated an agent, phenylbutyric acid, that ameliorates cell death in murine astrocytes infected with ts1 MoMuLV (ts1). Phenylbutyric acid, an aromatic short chain fatty acid, was shown to prevent the loss of catalase that occurs in ts1 infected astrocytes, and to prevent ts1-mediated cell death. Cell cotransfection studies demonstrated that phenylbutyric acid activates peroxisome proliferator receptors (PPARs) in astrocytes, and binds to the peroxisome proliferator-activated receptors alpha and gamma. This observation suggests that the effects of PBA may be mediated by PPARs in astrocytes. Phenylbutyric acid also maintained catalase protein levels in brain of ts1-infected mice, and delayed the hindlimb paralysis caused by ts1 infection. Because PBA activates peroxisome proliferator-activated receptors and prevents loss of catalase, we suggest that ts1-induced oxidative stress in infected astrocytes that is alleviated by PBA is mediated via PPARalpha and/or PPARgamma.