Age‐related and cancer‐related epigenomic modifications have been associated with enhanced cell‐to‐cell gene expression variability that characterizes increased cellular stochasticity. Since gene expression variability appears to be highly reduced by—and epigenetic and phenotypic stability acquired through—direct or long‐range cellular interactions during cell differentiation, we propose a common origin for aging and cancer in the failure to control cellular stochasticity by cell–cell interactions. Tissue‐disruption‐induced cellular stochasticity associated with epigenetic drift would be at the origin of organ dysfunction because of an increase in (...) phenotypic variation among cells, ultimately leading to cell death and organ failure through a loss of coordination in cellular functions, and eventually to cancerization. We propose mechanistic research perspectives to corroborate this hypothesis and explore its evolutionary consequences, highlighting a positive correlation between the median age of mass loss onset (a proxy for the onset of organ aging) and the median age at cancer diagnosis. (shrink)

Transmissible cancers are elusive and understudied parasitic life forms caused by malignant clonal cells (nine lineages are known so far). They emerge by completing sequential steps that include breaking cell cooperation, evade anti‐cancer defences and shedding cells to infect new hosts. Transmissible cancers impair host fitness, and their importance as selective force is likely largely underestimated. It is, therefore, crucial to determine how common they might be in the wild. Here, we draw a parallel between the steps required for a (...) transmissible cancer to emerge and the steps required for an intelligent civilisation to emerge in the Milky Way using a modified Drake equation. Using numerical analyses, we estimate the potential number of extant marine and bivalve species in which transmissible cancers might exist. Our results suggest that transmissible cancers are more common than expected, and that new lineages can be found by screening a large number of species. (shrink)

From an evolutionary perspective, both atavism and somatic evolution/convergent evolution theories can account for the consistent occurrence, and astounding attributes of cancers: being able to evolve from a single cell to a complex organized system, and malignant transformations showing significant similarities across organs, individuals, and species. Here, we first provide an overview of these two hypotheses, including the possibility of them not being mutually exclusive, but rather potentially representing the two extremes of a continuum in which the diversity of cancers (...) can emerge. In reviewing the current literature, we also discuss the criteria that should be applied to discriminate between the two competing theories and to determine their relevant contributions to oncogenesis and cancer progression. Finally, we deliberate on the potential applications of this conceptual framework in developing novel treatment strategies. (shrink)

Similar to parasites, malignant cells exploit the host for energy, resources and protection, thereby impairing host health and fitness. Although cancer is widespread in the animal kingdom, its impact on life history traits and strategies have rarely been documented. Devil facial tumour disease, a transmissible cancer, afflicting Tasmanian devils, provides an ideal model system to monitor the impact of cancer on host life-history, and to elucidate the evolutionary arms-race between malignant cells and their hosts. Here we provide an overview of (...) parasite-induced host life history adaptations, then both phenotypic plasticity of LH responses and changes in allele frequencies that affect LH traits of Tasmanian devils in response to DFTD are discussed. We conclude that akin to parasites, cancer can directly and indirectly affect devil LH traits and trigger host evolutionary responses. Consequently, it is important to consider oncogenic processes as a selective force in wildlife. Exposure to transmissible cancer cells, i.e., Tasmanian devil facial tumour cells, can cause changes to life history traits either as the result of phenotypic plasticity in response to exposure during the lifetime of the individual or as the result of evolutionary change in LH traits due to selection over generations.Photo credits: Frédéric Thomas, Sarah Peck, Geordie Jennings. (shrink)

Similar to parasites, cancer cells depend on their hosts for sustenance, proliferation and reproduction, exploiting the hosts for energy and resources, and thereby impairing their health and fitness. Because of this lifestyle similarity, it is predicted that cancer cells could, like numerous parasitic organisms, evolve the capacity to manipulate the phenotype of their hosts to increase their own fitness. We claim that the extent of this phenomenon and its therapeutic implications are, however, underappreciated. Here, we review and discuss what can (...) be regarded as cases of host manipulation in the context of cancer development and progression. We elaborate on how acknowledging the applicability of these principles can offer novel therapeutic and preventive strategies. The manipulation of host phenotype by cancer cells is one more reason to adopt a Darwinian approach in cancer research. -/- . (shrink)

Stochastic gene expression plays a leading developmental role through its contribution to cell differentiation. It is also proposed to promote phenotypic diversification in malignant cells. However, it remains unclear if these two forms of cellular bet‐hedging are identical or rather display distinct features. Here we argue that bet‐hedging phenomena in cancer cells are more similar to those occurring in unicellular organisms than to those of normal metazoan cells. We further propose that the atavistic bet‐hedging strategies in cancer originate from a (...) hijacking of the normal developmental bet‐hedging of metazoans. Finally, we discuss the constraints that may shape the atavistic bet‐hedging strategies of cancer cells. (shrink)

BackgroundNeuroimaging studies have shown a complex pattern of brain activation during perception of a pleasant odor and during its olfactory imagery. To date, little is known regarding changes in motor cortex excitability during these tasks. Bergamot essential oil is extensively used in perfumes and cosmetics for its pleasantness. Therefore, to further our understanding of the human sense of smell, this study aimed to investigate the effect of perception and imagery of a pleasant odor on motor cortex using Transcranial magnetic stimulation.Materials (...) and MethodsWe examined the primary motor cortex excitability during perception of a pleasant odor or perception of odorless saline. Furthermore, we tested the effect of olfactory imagery of BEO on corticospinal excitability. The increase in motor evoked potential amplitude was correlated with personality dimensions scores, pleasantness, vividness, and general imagery ability.ResultsThe results indicate that the corticospinal excitability changed after both perception and imagery of a pleasant odor. The correlation analysis shows an association with neuroticism personality trait and with general olfactory imagery ability.ConclusionBoth perception of a pleasant odor and its olfactory imagery modulate motor cortex excitability. The enhanced brain activation is affected by specific individual characteristics. Overall, our findings provide physiological evidence for a complex interaction between the olfactory and motor systems. (shrink)

BackgroundHigh frequency repetitive transcranial magnetic stimulation of the left dorsolateral prefrontal cortex has shown significant efficiency in the treatment of resistant depression. However in healthy subjects, the effects of rTMS remain unclear.ObjectiveOur aim was to determine the impact of 10 sessions of rTMS applied to the DLPFC on mood and emotion recognition in healthy subjects.DesignIn a randomised double-blind study, 20 subjects received 10 daily sessions of active or sham rTMS. The TMS coil was positioned on the left DLPFC through neuronavigation. (...) Several dimensions of mood and emotion processing were assessed at baseline and after rTMS with clinical scales, visual analogue scales, and the Ekman 60 faces test.ResultsThe 10 rTMS sessions targeting the DLPFC were well tolerated. No significant difference was found between the active group and the control group for clinical scales and the Ekman 60 faces test. Compared to the control group, the active rTM... (shrink)

Graphical AbstractCancer is a complex disease, with sophisticated cellular mechanisms as the targets of evolutionary processes driven by random genetic and epigenetic mutations. Oncogenesis is evolutionarily linked to stem cell numbers/mutations and organ/body size; therefore, inter-disciplinary frameworks across different scales (cellular, tissue, organs and species) are necessary to decipher cancer progression.

This response discusses Mookherjee’s views on plural autonomy and autonomy-promoting education, and her recognition that different cultural value systems can lead to varied responses and strategies across cultures. It considers mechanisms to counter forced marriage and argues from the standpoint of grassroots work within the Muslim community for the importance of the distinction between traditional culture and religion. It raises the issues of racism, islamophobia, and stereotyping in silencing Muslim women’s voices and reducing the space for them to argue for (...) change within communities. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:Buddhist and Catholic Monks Talk about CelibacyThomas Ryan, CSPThe electronic sign at the Minneapolis–St. Paul airport was flashing "Orange Alert" as a dozen Buddhist monks arrived in their burnt orange robes from around the country for three days of dialogue on celibacy with a similar number of Catholic monastics come together from various monasteries at St. John's Abbey in Collegeville, Minnesota. As he opened the October 26–29, 2006, meeting, (...) Rev. William Skudlarek, executive director of Monastic Interreligious Dialogue (MID), said, "You (Buddhists) have been at this for some five-to-seven hundred years longer than we have. We have something to learn."This was the second Monks in the West interreligious dialogue. The first took place in 2004 at the City of Ten Thousand Buddhas in northern California. On the Catholic side, the participants came from the Benedictine, Cistercian, and Camaldolese monasteries. On the Buddhist side, they came from the Theravada, Mahayana, and Tibetan traditions. Through the event, participants began the day with an hour of quiet sitting in meditation and joined the monastic community at St. John's for their rhythm of daily prayer.The first session dealt with theory, the "why" of celibacy. Buddhist participants explained that their teachings focus on seeing how suffering is created and cured. Attachments give rise to suffering, so advancement in the spiritual life requires letting go of one's attachments. Attachment to desires, among which are sexual desires, is a hindrance to spiritual progress. "Raging desire takes away choice, freedom," said Rev. Kusala Bhikshu, a Buddhist chaplain at UCLA, in his opening presentation. "The senses must be controlled in order to be free."Brother Gregory Perron from St. Procopius monastery in Indiana spoke of how monastic life demands a profound understanding and acceptance of solitude. "Celibacy is a tool," offered Perron, "a skillful means like intentional simplicity of life, by which our heart is burrowed out and the core of our being laid bare. By embracing it, the monk accepts the aloneness that characterizes every human being."In response to Buddhist reflections on the illusory nature of the body, Catholic participants pointed out Christianity's remarkably positive evaluation of the [End Page 143] body in the doctrines of the Incarnation, the bodily Resurrection and Ascension of Jesus, and the indwelling of the Holy Spirit. Both sides acknowledged balancing points of reference as well, such as, in Christianity, Paul's "Who will rescue me from this body of death?" (Rom 7:24). Though humankind ranks eighth from the bottom in Buddhism's thirty-two-realm cosmology, that level is the only one where spiritual growth can happen. Thus human form is in the end praised by the Buddha.In the second session, the participants moved from theory to practice. Rev. Jisho Perry from the Shasta Buddhist Abbey in California said that "the whole thrust of training is not to give in to desire that arises." He described the Buddhist method of accepting sexual feelings without either acting on them or repressing them, but just letting them pass through. "The right use of will is willingness, not willpower—the willingness to sit there and let that feeling pass through," he said.Fr. Skudlarek expressed appreciation for this Buddhist approach to transforming the sexual energy. "I never got a sense in our training of accepting the feeling with awareness and letting it pass without acting on it. You had to fight it! And the more you resisted, the stronger it got!"Rev. Heng Sure, who teaches at the Graduate Theological Union in Berkeley, presented celibacy as the first step in a three-step process that goes from celibacy to stillness to insight. "It should not be seen just as a difficult adjunct to the spiritual path, but as essential to it," he said. The practice of meditation represents daily periods when the senses are stilled and not allowed to pursue sense objects. "Something happens to the energy in the stillness; the pressure goes away." In married life, he explained, spiritual practice is "partial and piecemeal," making celibacy a more effective means to move toward insight and the peace and happiness that flow from it. In the discussion, Benedictine Fr. Mark... (shrink)

In lieu of an abstract, here is a brief excerpt of the content:Buddhist-Christian Studies 23 (2003) 143-145 [Access article in PDF] Catholic and Buddhist Monastics Focus on Suffering Thomas Ryan Paulist Office for Ecumenical and Interfaith Relations Approximately twenty Benedictine, Trappist, and Camaldolese men and women monastics met from April 13-18 with an equal number of Buddhist monastics at the Trappist Gethsemani monastery in Kentucky for five days of dialogue on the causes of suffering. The encounter, Gethsemani II, was a (...) sequel to a similar 1996 meeting at the monastery made famous by the monk Thomas Merton, a noted twentieth-century contemplative and peace activist who died in 1968. Merton's friendship with the Dalai Lama served as seminal inspiration for these two Buddhist-Christian dialogues. In a ritual at the opening of the Gethsemani II meeting, the participants, joined by a few advisors and observers to the dialogue, hung a wreath of flowers around the cross marking Merton's grave.Each day speakers from both sides initiated a conversation on a particular cause of suffering, such as greed and consumerism, personal and structural violence, sickness and aging. "I do not do well at conferences, and I came prepared to be bored," said John Daido Loori, abbot of the Zen Mountain monastery in Mount Tremper, New York, on day three, "but the level of honesty and depth of sharing in these exchanges has ripped open my heart."It is not possible in this forum to synthesize the penetrating reflections and stories on suffering offered by the participants.What may be even more important is the window offered by this dialogue into the dynamics of interfaith encounter no matter where it takes place.By sharing times of prayer, talk, meals, and rituals appropriate to each tradition, the participants became friends. They came for one thing, to talk about suffering, and in the process found another: an experience of community. They began each conversation with the musical and meditative interlude of a recorder, but the openness and sensitivity of the conversation itself became the real music. They didn't solve a single problem, but they kindled a vital force—friendship—with which to confront problems together in the future. Each brought passion for their own tradition—the gospel on the one hand and the dharma on the other—and each ended by recognizing in the other a powerful resource for healing the world.Evident in this dialogue was the emergence of a Euro-American Buddhist voice, [End Page 143] deeply respectful of the Asian tradition inherited, yet willing to think creatively about possible bridge points of understanding, of comparison, of ways of reformulating set patterns of saying things so as to better get at possible common meanings.One example of this will suffice. Suffering is at the heart of the Buddha's teachings in the Four Noble Truths, the first teachings he gave after his experience of enlightenment. First, all existence is dukkha, unsatisfactory and filled with suffering. Second, dukkha arises from tanha, a craving or clinging, which means a constant effort to find something permanent and stable in a transient world. Third, dukkha can cease totally, and this is Nirvana. Fourth, Nirvana can be reached by following the Eightfold Path described as "right" or samma: right understanding, right directed thought, right speech, right action, right livelihood, right effort, right mindfulness, right concentration. In short, the first three wisdom sayings relate to the existence, the cause, and the cessation of suffering. The fourth offers a clearly laid-out plan for liberation from suffering.The Christian approach could be typified in Pope John Paul II's 1984 Apostolic Letter "On the Meaning of Christian Suffering," which was distributed to all the participants. In reflecting on Jesus nailed to the cross, the pope observes that "in this weakness there is accomplished his lifting up, confirmed by the power of the resurrection. This means that the weaknesses of all human sufferings are capable of being infused with the same power of God manifested in Christ's cross. In such a concept, to suffer means to become particularly susceptible, particularly open, to the working of the salvific powers of God offered... (shrink)

In lieu of an abstract, here is a brief excerpt of the content:Gethsemani II:Catholic and Buddhist Monastics Focus on SufferingThomas Ryan, CSPApproximately twenty Benedictine, Trappist, and Camaldolese men and women monastics met 13-18 April 2003 with an equal number of Buddhist monastics at the Trappist Gethsemani monastery in Kentucky for five days of dialogue on the causes of suffering. The encounter, Gethsemani II, was a sequel to a similar 1996 meeting at the monastery made famous by the monk Thomas Merton, (...) a noted twentieth-century contemplative and peace activist who died in 1968. Merton's friendship with the Dalai Lama served as seminal inspiration for these two Buddhist-Christian dialogues. In a ritual at the opening of the Gethsemani II meeting, the participants, joined by a few advisors and observers to the dialogue, hung a wreath of flowers around the cross marking Merton's grave.Each day speakers from both sides initiated a conversation on a particular cause of suffering, such as greed and consumerism, personal and structural violence, sickness and aging. "I do not do well at conferences, and I came prepared to be bored," said John Daido Loori, abbot of the Zen Mountain monastery in Mt. Tremper, NY, on day three, "but the level of honesty and depth of sharing in these exchanges has ripped open my heart." It is not possible in this forum to synthesize the penetrating reflections and stories on suffering offered by the participants. What may be even more important is the window offered by this dialogue into the dynamics of interfaith encounter no matter where it takes place.By sharing times of prayer, talk, meals, and rituals appropriate to each tradition, the participants became friends. They came for one thing—to talk about suffering—and in the process found another: an experience of community. They began each conversation with the musical and meditative interlude of a recorder, but the openness and sensitivity of the conversation itself became the real music. They didn't solvea single problem, but they kindled a vital force—friendship—with which to confront problems together in the future. Each brought passion for their own tradition, the gospel on the one hand and the dharma on the other, and each ended by recognizing in the other a powerful resource for healing the world.Evident in this dialogue was the emergence of a Euro-American Buddhist voice, deeply respectful of the Asian tradition inherited, yet willing to think creatively about possible bridge points of understanding, of comparison, of ways of reformulating set [End Page 249] patterns of saying things so as to better get at possible common meanings. One example of this will suffice. Suffering is at the heart of the Buddha's teachings in the Four Noble Truths, the first teachings he gave after his experience of enlightenment. First, all existence is dukkha, unsatisfactory and filled with suffering. Second, dukkha arises from tanha, a craving or clinging, which means a constant effort to find something permanent and stable in a transient world. Third, dukkha can cease totally, and this is nirvana. Fourth, this can be reached by following the Eightfold Path described as "right" or samma: right understanding, right directed thought, right speech, right action, right livelihood, right effort, right mindfulness, right concentration. In short, the first three wisdom sayings relate to the existence, the cause, and the cessation of suffering. The fourth offers a clearly laid out plan for liberation from suffering.The Christian approach could be typified in Pope John Paul II's 1984 Apostolic Letter "On the Meaning of Christian Suffering," which was distributed to all the participants. In reflecting on Jesus nailed to the cross, the pope observes that "in this weakness there is accomplished his lifting up, confirmed by the power of the resurrection. This means that the weaknesses of all human sufferings are capable of being infused with the same power of God manifested in Christ's cross. In such a concept, to suffer means to become particularly susceptible, particularly open, to the working of the salvific powers of God offered humanity in Christ. In him God has confirmed his desire to act especially through suffering... and wishes to make his power known precisely in this weakness and emptying of self" (p... (shrink)

Examines how Stieglitz's work influenced Gertrude Stein, William Carlos Williams, Hart Crane and Sherwood Anderson and discusses how photography reshaped literary aesthetics.