The Y chromosome in the XY sex-determination system is often shorter than its X counterpart, a condition attributed to degeneration after Y recombination ceases. Contrary to the traditional view of continuous, gradual degeneration, our study reveals stabilization within large mating populations. In these populations, we demonstrate that both mutant and active alleles on the Y chromosome can reach equilibrium through a mutation-selection balance. However, the emergence of a new species, particularly through the founder effect, can disrupt this equilibrium. (...) Specifically, if the male founders of a new species carry only a mutant allele for a particular Y-linked gene, this allele becomes fixed, leading to the loss of the corresponding active gene on the Y chromosome. Our findings suggest that the rate of Y-chromosome degeneration may be linked to the frequency of speciation events associated with single-male founder events. (shrink)

Loss of the Y‐chromosome is a common feature of species with chromosomal sex determination. However, our understanding of why some lineages frequently lose Y‐chromosomes while others do not is limited. The fragile Y hypothesis proposes that in species with chiasmatic meiosis the rate of Y‐chromosome aneuploidy and the size of the recombining region have a negative correlation. The fragile Y hypothesis provides a number of novel insights not possible under traditional models. Specifically, increased rates of Y aneuploidy (...) may impose positive selection for (i) gene movement off the Y; (ii) translocations and fusions which expand the recombining region; and (iii) alternative meiotic segregation mechanisms (achiasmatic or asynaptic). These insights as well as existing evidence for the frequency of Y‐chromosome aneuploidy raise doubt about the prospects for long‐term retention of the human Y‐chromosome despite recent evidence for stable gene content in older non‐recombining regions. (shrink)

Studies of Y chromosome evolution often emphasize gene loss, but this loss has been counterbalanced by addition of new genes. The DAZ genes, which are critical to human spermatogenesis, were acquired by the Y chromosome in the ancestor of Old World monkeys and apes. We and our colleagues recently sequenced the rhesus macaque Y chromosome, and comparison of this sequence to human and chimpanzee enables us to reconstruct much of the evolutionary history of DAZ. We (...) report that DAZ arrived on the Y chromosome about 38 million years ago via the transposition of at least 1.1 megabases of autosomal DNA. This transposition also brought five additional genes to the Y chromosome, but all five genes were subsequently lost through mutation or deletion. As the only surviving gene, DAZ experienced extensive restructuring, including intragenic amplification and gene duplication, and has been the target of positive selection in the chimpanzee lineage.Editor's suggested further reading in BioEssays Should Y stay or should Y go: The evolution of non‐recombining sex chromosomes Abstract. (shrink)

Mammalian sex chromosomes exhibit marked sexual dimorphism in behavior during gametogenesis. During oogenesis, the X chromosomes pair and participate in unrestricted recombination; both are transcriptionally active. However, during spermatogenesis the X and Y chromosomes experience spatial restriction of pairing and recombination, are transcriptionally inactive, and form a chromatin domain that is markedly different from that of the autosomes. Thus the male germ cell has to contend with the potential loss of X‐encoded gene products, and it appears that coping strategies (...) have evolved. Genetic control of sex‐chromosome inactivation during spermatogenesis does not involve pairing or the presence of the Y chromosome or an intact X chromosome, and may therefore be under exogenous control by the gonad. Sex‐chromosome reactivation during oogenesis and inactivation during spermatogenesis probably reflect specific meiotic events such as recombination. Understanding these phenomena may help explain other sex‐related differences in genetic recombination. (shrink)

The creeping vole Microtus oregoni exhibits remarkably transformed sex chromosome biology, with complete chromosome drive/drag, X‐Y fusions, sex reversed X complements, biased X inactivation, and X chromosome degradation. Beginning with a selfish X chromosome, I propose a series of adaptations leading to this system, each compensating for deleterious consequences of the preceding adaptation: (1) YY embryonic inviability favored evolution of a selfish feminizing X chromosome; (2) the consequent Y chromosome transmission disadvantage favored X‐Y fusion (...) (“XP”); (3) Xist‐based silencing of Y‐derived XP genes favored a second X‐Y fusion (“XM”); (4) X chromosome dosage‐related costs in XPXM males favored the evolution of XM loss during spermatogenesis; (5) X chromosomal dosage‐related costs in XM0 females favored the evolution of XM drive during oogenesis; and (6) degradation of the non‐recombining XP favored the evolution of biased X chromosome inactivation. I discuss recurrent rodent sex chromosome transformation, and selfish genes as a constructive force in evolution. (shrink)

Sex chromosomes in plants have been known for a century, but only recently have we begun to understand the mechanisms behind sex determination in dioecious plants. Here, we discuss evolution of sex determination, focusing on Silene latifolia, where evolution of separate sexes is consistent with the classic “two mutations” model—a loss of function male sterility mutation and a gain of function gynoecium suppression mutation, which turned an ancestral hermaphroditic population into separate males and females. Interestingly, the gynoecium suppression function (...) in S. latifolia evolved via loss of function in at least two sex‐linked genes and works via gene dosage balance between sex‐linked, and autosomal genes. This system resembles X/A‐ratio‐based sex determination systems in Drosophila and Rumex, and could represent a steppingstone in the evolution of X/A‐ratio‐based sex determination from an active Y system. (shrink)

The human Y chromosome contains very low levels of nucleotide variation. It has been variously hypothesized that this invariance reflects historic reductions in the human male population, a very recent common ancestry, a slow rate of molecular evolution, an inability to evolve adaptively, or frequent selective sweeps acting on genes borne on the Y chromosome. We propose an alternative theory in which human Y chromosome evolution is driven by mutations in the maternally inherited mitochondrial genome, which impair (...) male fertility and ultimately lead to a reduction in the effective population size (Ne) and consequently the variability of the Y chromosome. BioEssays 24:275–279, 2002. © 2002 Wiley Periodicals, Inc.; DOI 10.1002/bies.10062. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:XY/XOLianne SimonAs a boy child I might once have thrived, but the loss of a Y chromosome in one of the first few cell divisions left me a faie half–girl struggling for life—like some changeling left in place of a human baby. My genetic mosaic of XY and XO cell lines created a fetal legacy of Turner Syndrome medical issues. Among these were delayed growth, a largely (...) absent puberty, and micrognathia—a small jaw that feminized my face. [End Page E11]At two I weighed just eighteen pounds. My parents worried they might lose their little boy, I was that frail. All I knew was I was the smallest of my peer group and had a cute pixie face. I imagined myself a high–spirited elfin princess, but was in truth shy—almost timid—and prone to tears.I first responded to the Gospel at vacation Bible school. One of the women there read me Bible stories. I didn’t understand them all, but I wanted to love Jesus and be a good girl.At nine I was the size of a 6–year–old. By then I’d started growing faster, so my mother stopped taking me to the doctors. I didn’t see one again until an emergency appendectomy in college.Fifth grade brought surprises. Jim melted my heart with his Beatles love songs and cute smile. I dreamed of being his bride. Karen was the first classmate ever shorter than me. We were best friends, but one day the principal said I should play softball with the boys instead of hopscotch with her.My parents allowed me dolls and tea sets, even an Easy–Bake oven. But wearing my sister’s clothes triggered a sad–eyed lecture—boys didn’t do such things. No dresses. No talking with my hands. No long hair. And no crushes on boys.If I prayed hard enough, if I was really good, maybe God would make me a real boy—tall and strong, fast and agile—like my older brother. Two years later, puberty cracked my high–pitched squeal of a voice and sent it sliding down to a mellower soprano. I grew taller, but didn’t get muscles or body hair, and I remained hopelessly uncoordinated. An inguinal hernia kept me from running very far.High school turned my prayers into pleas for mercy. I despaired of ever fitting in. Some Christians might not have welcomed a feminine boy, but the pastor of our Southern Baptist mission considered me one more sinner in need of the saving grace of a forgiving God. He led me to faith in Christ. As a new believer, I assumed I could be a boy for real. Maybe even find a girlfriend. Instead, the mask that allowed me to function socially crumbled, leaving me no place to hide.In the spring of 1970, I registered for the draft. Me fighting in Vietnam seemed a real possibility. Or at least spending time in prison for refusing induction. Except that a delicate intersex kid would never have passed the physical. Nearly perfect SAT scores won me a scholarship to Miami, so I left a supportive home in Illinois for a boys’ dorm in south Florida.My surname then was Klett. The worst of the guys called me Clit, or sometimes Clitoris. Others derided my small size and lack of virility. One propositioned me. Another used to pin me to my bed and lie on top of me until I quit struggling. Though he stopped each time I surrendered, my defenses lay in ruin.A few of the boys were nice. David took me for long rides on his motorcycle, with my arms wrapped tight around his waist. He treated me with gentle kindness and asked nothing in return.To escape the dorm, I studied in the library stacks, where only honors and graduate students were allowed. The next year I found a derelict building where the university stored old theatrical sets. It even had a quiet place to sit in the sun. Best of all—nobody ever went there.One day my imagination wandered through the wardrobe. What would I have worn... (shrink)

The special properties of the Y chromosome stem form the fact that it is a non‐recombining degenerate derivative of the X chromosome. The absence of homologous recombination between the X and the Y chromosome leads to gradual degeneration of various Y chromosome genes on an evolutionary timescale. The absence of recombination, however, also favors the accumulation of transposable elements on the Y chromosome during its evolution, as seen with both Drosophila and mammalian Y chromosomes. Alongside (...) these processes, the acquisition and amplification of autosomal male benefit genes occur. This review will focus on recent studies that reveal the autosome‐acquired genes on the Y chromosome of both Drosophila and humans. The evolution of the acquired and amplified genes on the Y chromosome is also discussed. Molecular and comparative analyses of Y‐linked repeats in the Drosophila melanogaster genome demonstrate that there was a period of their degeneration followed by a period of their integration into RNAi silencing, which was beneficial for male fertility. Finally, the function of non‐coding RNA produced by amplified Y chromosome genetic elements will be discussed. BioEssays 27:1256–1262, 2005. © 2005 Wiley Periodicals, Inc. (shrink)

The Y chromosomes of most Drosophila species are necessary for male fertility but they are not involved in sex determination. They have many puzzling properties that resemble the effects caused by B chromosomes. Classical genetic and molecular studies reveal substantial affinities between Y and B chromosomes and suggest that the Y chromosomes of Drosophila are not degenerated homologues of the X chromosomes, but rather that their Y chromosomes evolved as specialized supernumeraries similar to classical B chromosomes.

Mammals have an XX:XY system of chromosomal sex determination in which a small heterochromatic Y controls male development. The Y contains the testis determining factor SRY, as well as several genes important in spermatogenesis. Comparative studies show that the Y was once homologous with the X, but has been progressively degraded, and now consists largely of repeated sequences as well as degraded copies of X linked genes. The small original X and Y have been enlarged by cycles of autosomal addition (...) to one partner, recombination onto the other and continuing attrition of the compound Y. This addition–attrition hypothesis predicts that the pseudoautosomal region of the human X is merely the last relic of the latest addition. Genes (including SRY) on the conserved or added region of the Y evolved functions in male sex determination and differentiation distinct from the general functions of their X‐linked partners. Although the gonadogenesis pathway is highly conserved in vertebrates, its control has probably changed radically and rapidly in vertebrate – even mammalian – evolution. (shrink)

PURPOSE:To report the localization of a gene causing drusen and macular degeneration in a previously undescribed North American family. METHODS:Genetic mapping studies were performed using linkage analysis in a single family with drusen and atrophic macular degeneration. RESULTS:The clinical manifestations in this family ranged from fine macular drusen in asymptomatic middle-aged individuals to atrophic macular lesions in two children and two elderly patients. We mapped the gene to chromosome 6q14 between markers D6S2258 and D6S1644. CONCLUSIONS:In a family with autosomal (...) dominant drusen and atrophic macular degeneration, the gene maps to a 3.2-cM region on chromosome 6q14. This locus appears to be distinct from, but adjacent to, the loci for cone-rod dystrophy 7 (CORD7) and North Carolina macular dystrophy (MCDR1). Future identification of the gene responsible for the disease in this family will provide a better understanding of macular degeneration. (shrink)

Gradual degradation seems inevitable for non‐recombining sex chromosomes. This has been supported by the observation of degenerated non‐recombining sex chromosomes in a variety of species. The human Y chromosome has also degenerated significantly during its evolution, and theories have been advanced that the Y chromosome could disappear within the next ∼5 million years, if the degeneration rate it has experienced continues. However, recent studies suggest that this is unlikely. Conservative evolutionary forces such as strong purifying selection and intrachromosomal (...) repair through gene conversion balance the degeneration tendency of the Y chromosome and maintain its integrity after an initial period of faster degeneration. We discuss the evidence both for and against the extinction of the Y chromosome. We also discuss potential insights gained on the evolution of sex‐determining chromosomes by studying simpler sex‐determining chromosomal regions of unicellular and multicellular microorganisms. (shrink)

The determination of death by neurological criteria remains controversial scientifically, culturally, and legally, worldwide. In the United Kingdom, although the determination of death by neurological criteria is not legally codified, the Code of Practice of the Academy of Medical Royal Colleges is customarily used for neurological death determination and treatment withdrawal. Unlike some states in the US, however, there are no provisions under the law requiring accommodation of and respect for residents' religious rights and commitments when secular conceptions of death (...) based on medical codes and practices conflict with a traditional concept well-grounded in religious and cultural values and practices. In this article, we analyse the medical, ethical, and legal issues that were generated by the recent judgement of the High Court of England and Wales in Re: A [2015] EWHC 443. Mechanical ventilation was withdrawn in this case despite parental religious objection to a determination of death based on the code of practice. We outline contemporary evidence that has refuted the reliability of tests of brainstem function to ascertain the two conjunctive clinical criteria for the determination of death that are stipulated in the code of practice: irreversible loss of capacity for consciousness and somatic integration of bodily biological functions. We argue that: the tests of brainstem function were not properly undertaken in this case; the two conjunctive clinical criteria set forth in the code of practice cannot be reliably confirmed by these tests in any event; and absent authentication of the clinical criteria of death, the code of practice wrongly invokes a secular definition of death based on the loss of personhood. Consequently, the moral obligation of a pluralistic society to honor and respect diverse religious convictions to the greatest extent possible is being violated. Re A is contrasted with the US case of Jahi McMath in which the court accommodated parental religious objection to the determination of neurological death codified in the Uniform Determination of Death Act. We conclude that the legal system in the United Kingdom should not favour a secular definition of death over a definition of death that is respectful of religious values about the inviolability and sanctity of life. We recommend the legal recognition of religious accommodation in death determination to facilitate cultural sensitivity and compassionate care to patients and families in a pluralistic society. (shrink)

There is a need for empirically based research on social and ethical challenges related to informed consent processes, particularly in studies focusing on adolescent sexual and reproductive health. In a pilot study of a school-based pregnancy prevention intervention in rural Zambia, the majority of the guardians who were asked to consent to their daughters’ participation, refused. In this paper we explore the reasons behind the low participation in the pilot with particular attention to challenges related to the community engagement and (...) informed consent process. The pilot was implemented in two schools and examined the acceptability of a package of interventions including economic support to families to keep their girls in school, pocket money for girls, youth club meetings on reproductive health, and community meetings to sensitize the community. Focus group discussions were conducted with girls who participated in the pilot, boys in their class and with parents. Individual semi-structured interviews were conducted with teachers, peer educators and community health workers involved in the coordination of the intervention as well as with religious and traditional leaders. Data were analyzed through thematic analysis. The findings indicate that inadequate use of recognized community communication channels during the community engagement process and dissemination of information about the pilot resulted in limited understanding of the pilot concept by the community. This surfaced through uncertainty and fear that the intervention may result in loss of control over daughters, worries about why money was provided unconditionally to girls, and suspicion of links to satanism. The sense of insecurity appeared to be exacerbated by low literacy levels, poverty, fear of loss of bride wealth, perceived disregard for local perceptions of social status, and scanty trust in the actors implementing the pilot. Inadequate use of locally appropriate channels in the dissemination of information created room for interpretation and facilitated development of mistrust, undermining the conditions for community engagement and actual informed consent. A key lesson learnt is the importance of taking seriously the complexity of local values and structures that may impact people’s capability to consent or not consent to a study in an informed manner. (shrink)

The perinatal necropsy is an important investigation following fetal or neonatal loss. Legal requirements on registration decree that consent is needed before necropsy can proceed in some of these babies. However, there are ill-defined grey areas which are open to legal and ethical difficulties. This paper discusses the problems that can arise with consent for a necropsy in the perinatal period. Some of these problems are clearly legal or ethical but all can cause distress to parents at a time (...) of grief and bereavement. The issues may not be readily resolved but public debate and ad hominem decisions on each perinatal loss may help to alleviate the problems. (shrink)

_ Purpose. _ The article highlights, on the one hand, the impact of the potential of a developed reflective identity on the processes of civilizational transformations, and on the other hand, the role of the transformational processes of a civilizational scale in the formation of a new type of reflective identity. Acute crisis processes in social development, which humanity has faced so far, in particular after 24.02.2022, indicate the beginning of a radical civilizational transformation. Therefore, in the article, it is (...) necessary to find out with the help of which mental, organizational and personal resources humanity can move to a more developed level of civilization without much loss. It is also necessary to show the importance of the philosophical understanding of reality in the formation of reflective identity because reflection has been the basic method of philosophy since its appearance. _Theoretical basis._ There is an understanding of the inextricable connection between the level of development of civilization and the level of reflective development of the individual fixed in a certain type of identity: a more historically developed stage of civilization corresponds to a more complex type of identity with multi-level reflection. At the same time, achieving a higher level of civilizational development is possible only under the condition of constructing a more complex and multi-level reflexive identity. _Originality._ It consists in establishing that the mental-cognitive mechanisms of reflection during the development of civilization passed through the stages of 1) reflexive forms of "the Axial Age", fixed in the corresponding forms of moral, logical, theological, political, etc. culture since the era of Ancient society; 2) reflexive forms of the Modern era with an emphasis on the inner world of man, the emergence of the reflective division into subject and object of knowledge as an essential feature of epistemology, as well as the formation of a modern type of identity; 3) the dual reflection of the post-industrial society and the Second Modern era, the mechanisms of which contribute to the formation of an active and self-sufficient network society and network crowdfunding economy. In this regard, at various stages of the development of civilization, in accordance with certain reflexive mechanisms, the corresponding types of identity are formed: 1) the basic identity of a person determined by his primary socialization; 2) reflective identity which is associated with the acquired cultural potential of a person and the opportunity to consciously choose special features of one’s own identity, and 3) identity which is associated with the existence in a given social culture of a mechanism of double reflection, which allows not only to make a valuable choice of the trajectory of development own identity but also to construct it. _Conclusions._ The aggravation of the identity problem in the modern world is the result of a civilizational crisis associated with the transformation of modern civilization, the technological basis of which is the introduction of renewable energy and artificial intelligence, as well as the development of network relationships in society. The hierarchical structure of modern identity is conditioned by the gradual historical and civilizational layering of the process of evolution of the reflexive component of identity. In each specific modern society, progressive civilizational transformations take place when an innovative type of identity coexisting with basic and modern types is activated and takes a leadership position. The growing role of network relations in society overcomes the identity crisis due to the reduction of social opposition and the harmonization of different aspects of the identity itself. Perceptible climatic changes and the destruction of the established security system in the world after 24.02.2022 made it obvious to the global thinking public that the world community is at the bifurcation point of a radical civilizational transformation. (shrink)

Contemporary bioethics is usually notable for its focus on the uses and abuses of biomedical technology, on personal liberty and the on the formulation of ethical problems as dilemmas to be solved by utilitarian calculus within the frameworks of committees and institutional guidelines. It is argued that these developments actually reflect a technologization of medical ethics itself, which more often relies non-personal algorithms of utility.This is explained, from a historical point of view, by the impact of technology on the concepts (...) of nature and naturalism and by the triumphs of modern science, which obscures non-scientific modes of discourse. The article acknowledges some benefits of the technologization of ethics such as the democratization of decision-making but the discussion concentrates on five arguments against the dominance of utilitarianism in medical ethics. The common denominator of these arguments is that utilitarianism fails its own standards by undermining trust in the public domain. The loss of trust is brought about by the displacement of the phenomenological self and from fostering adversarialism in ethical discourse. (shrink)

In the selection of job candidates who have the mental ability to become professional ATCOs, psychometric testing has been a ubiquitous activity in the ATM domain. To contribute to psychometric research in the ATM domain, we investigated the extent to which spatial orientation ability (SOA), as conceptualized in the spatial cognition and navigation literature, predicted air traffic conflict detection performance in a simulated free route airspace (FRA) environment. The implementation of free route airspace (FRA) over the past few years, notably (...) in Europe, have facilitated air traffic services by giving greater flexibility to aviation operators in planning and choosing preferred air routes that can lead to quicker arrivals. FRA offers enhanced system safety and efficiency, but these benefits can be outweighed by the introduction of air traffic conflicts that are geometrically more complex. Such conflicts can arise from increased number and distribution of conflict points, as well as from elevated uncertainty in aircraft maneuvering (for instance, during heading changes). Overall, these issues will make conflict detection more challenging for air traffic controllers (ATCOs). Consequently, there is a need to select ATCOs with suitably high levels of spatial orientation ability (SOA) to ensure flight safety under FRA implementation. In this study, we tested 20 participants who are eligible for ATCO job application, and found that response time-based performance on a newly developed, open access, computerized spatial orientation test (SOT) predicted time to loss of minimum separation (tLMS) performance on an air traffic conflict detection task (AT-CDT) we designed. We found this predictive relationship to be significant to a moderately large extent under scenarios with high air traffic density (raw regression coefficient = 0.58). Moreover, we demonstrated our AT-CDT as a valid test in terms of eliciting well-known mental workload and spatial learning effects. We explained these findings in light of similar or overlapping mental processes that were most likely activated optimally under task conditions featuring approximately equal numbers of outcome-relevant stimuli. We conclude by discussing the further application of the SOT to the selection of prospective ATCOs who can demonstrate high levels of conflict detection performance in FRA during training simulations. (shrink)

The determination of death by neurological criteria remains controversial scientifically, culturally, and legally, worldwide. In the United Kingdom, although the determination of death by neurological criteria is not legally codified, the Code of Practice of the Academy of Medical Royal Colleges is customarily used for neurological death determination and treatment withdrawal. Unlike some states in the US, however, there are no provisions under the law requiring accommodation of and respect for residents' religious rights and commitments when secular conceptions of death (...) based on medical codes and practices conflict with a traditional concept well-grounded in religious and cultural values and practices. In this article, we analyse the medical, ethical, and legal issues that were generated by the recent judgement of the High Court of England and Wales in Re: A [2015] EWHC 443. Mechanical ventilation was withdrawn in this case despite parental religious objection to a determination of death based on the code of practice. We outline contemporary evidence that has refuted the reliability of tests of brainstem function to ascertain the two conjunctive clinical criteria for the determination of death that are stipulated in the code of practice: irreversible loss of capacity for consciousness and somatic integration of bodily biological functions. We argue that: the tests of brainstem function were not properly undertaken in this case; the two conjunctive clinical criteria set forth in the code of practice cannot be reliably confirmed by these tests in any event; and absent authentication of the clinical criteria of death, the code of practice wrongly invokes a secular definition of death based on the loss of personhood. Consequently, the moral obligation of a pluralistic society to honor and respect diverse religious convictions to the greatest extent possible is being violated. Re A is contrasted with the US case of Jahi McMath in which the court accommodated parental religious objection to the determination of neurological death codified in the Uniform Determination of Death Act. We conclude that the legal system in the United Kingdom should not favour a secular definition of death over a definition of death that is respectful of religious values about the inviolability and sanctity of life. We recommend the legal recognition of religious accommodation in death determination to facilitate cultural sensitivity and compassionate care to patients and families in a pluralistic society. (shrink)

The COVID-19 pandemic shocked the global economy, with numerous companies suffering losses and shutting down. However, some companies proved to be resilient, being able to sustain their economic performance despite the pandemic. The study aims to explain the sustainable economic performance of companies during the COVID-19 pandemic. The relationships between empowering leadership, innovative work behavior, organizational readiness to change, and sustainable economic performance were assessed. The data were collected via an online questionnaire from January 2021 to March 2021, during the (...) height of the COVID-19 pandemic in Russia. The respondents were Russian companies’ employees holding management positions, competent to objectively assess organizational circumstances during the COVID-19 pandemic. A sample of 337 was used in the analysis. Confirmatory factor analysis (CFA) with maximum likelihood estimation was conducted using SPSS AMOS. The structural model was tested with standardized parameter estimates, standard errors, and p-values calculated. The findings of the study suggest that innovative work behavior and organizational readiness to learn have a direct influence on sustainable economic performance. The findings also suggest that empowering leadership impacts innovative work behavior but not sustainable economic performance. The mediation analysis indicates that innovative work behavior is a mediator between empowering leadership and sustainable economic performance, whereas organizational readiness to learn is not a moderator. The study adds to the leadership and sustainability body of knowledge and contributes to the research on the COVID-19 pandemic in the organizational context. (shrink)

The application of in vivo genetic lineage tracing has advanced our understanding of cellular mechanisms for tissue renewal in organs with slow turnover, like the lung. These studies have identified an adult stem cell with very different properties than classically understood ones that maintain continuously cycling tissues such as the intestine. A portrait has emerged of an ensemble of cellular programs that replenish the cells that line the gas exchange (alveolar) surface, enabling a response tailored to the extent of cell (...) loss. A capacity for differentiated cells to undergo direct lineage transitions allows for local restoration of proper cell balance at sites of injury. We present these recent findings as a paradigm for how a relatively quiescent tissue compartment can maintain homeostasis throughout a lifetime punctuated by injuries ranging from mild to life‐threatening, and discuss how dysfunction or insufficiency of alveolar repair programs produce serious health consequences like cancer and fibrosis. (shrink)

Background Bioethics and law distinguish between the practices of "physician-assisted death" and "allowing the patient to die." Discussion Advances in biotechnology have allowed medical devices to be used as destination therapy that are designed for the permanent support of cardiac function and/or respiration after irreversible loss of these spontaneous vital functions. For permanent support of cardiac function, single ventricle or biventricular mechanical assist devices and total artificial hearts are implanted in the body. Mechanical ventilators extrinsic to the body are (...) used for permanent support of respiration. Clinical studies have shown that destination therapy with ventricular assist devices improves patient survival compared to medical management, but at the cost of a substantial alteration in end-of-life trajectories. The moral and legal assessment of the appropriateness and permissibility of complying with a patient's request to electively discontinue destination therapy in a life-terminating act in non-futile situations has generated controversy. Some argue that complying with this request is ethically justified because patients have the right to request withdrawal of unwanted treatment and be allowed to die of preexisting disease. Other commentators reject the argument that acceding to an elective request for death by discontinuing destination therapy is 'allowing a patient to die' because of serious flaws in interpreting the intention, causation, and moral responsibility of the ensuing death. Summary Destination therapy with cardiac and/or ventilatory medical devices replaces native physiological functions and successfully treats a preexisting disease. We posit that discontinuing cardiac and/or ventilatory support at the request of a patient or surrogate can be viewed as allowing the patient to die if--and only if--concurrent lethal pathophysiological conditions are present that are unrelated to those functions already supported by medical devices in destination therapy. In all other cases, compliance with a patient's request constitutes physician-assisted death because of the pathophysiology induced by the turning off of these medical devices, as well as the intention, causation, and moral responsibility of the ensuing death. The distinction between allowing the patient to die and physician-assisted death is pivotal to the moral and legal status of elective requests for death by discontinuing destination cardiac and/or ventilatory medical devices in patients who are not imminently dying. This distinction also represents essential information that must be disclosed to patients and surrogates in advance of consent to this type of therapy. (shrink)

The spatial organization of the genome is intimately linked to its biological function, yet our understanding of higher order genomic structure is coarse, fragmented and incomplete. In the nucleus of eukaryotic cells, interphase chromosomes occupy distinct.

In 1968, the Harvard criteria equated irreversible coma and apnea with human death and later, the Uniform Determination of Death Act was enacted permitting organ procurement from heart-beating donors. Since then, clinical studies have defined a spectrum of states of impaired consciousness in human beings: coma, akinetic mutism, minimally conscious state, vegetative state and brain death. In this article, we argue against the validity of the Harvard criteria for equating brain death with human death. Brain death does not disrupt somatic (...) integrative unity and coordinated biological functioning of a living organism. Neurological criteria of human death fail to determine the precise moment of an organism’s death when death is established by circulatory criterion in other states of impaired consciousness for organ procurement with non-heart-beating donation protocols. The criterion of circulatory arrest 75 s to 5 min is too short for irreversible cessation of whole brain functions and respiration controlled by the brain stem. Brain -based criteria for determining death with a beating heart exclude relevant anthropologic, psychosocial, cultural, and religious aspects of death and dying in society. Clinical guidelines for determining brain death are not consistently validated by the presence of irreversible brain stem ischemic injury or necrosis on autopsy; therefore, they do not completely exclude reversible loss of integrated neurological functions in donors. The questionable reliability and varying compliance with these guidelines among institutions amplify the risk of determining reversible states of impaired consciousness as irreversible brain death. The scientific uncertainty of defining and determining states of impaired consciousness including brain death have been neither disclosed to the general public nor broadly debated by the medical community or by legal and religious scholars. Heart-beating or non-heart-beating organ procurement from patients with impaired consciousness is de facto a concealed practice of physician-assisted death, and therefore, violates both criminal law and the central tenet of medicine not to do harm to patients. Society must decide if physician-assisted death is permissible and desirable to resolve the conflict about procuring organs from patients with impaired consciousness within the context of the perceived need to enhance the supply of transplantable organs. (shrink)

Nucleotide diversity of the human Y chromosome is much lower than that in the rest of the genome. A new hypothesis postulates that this invariance may result from mutations in maternally inherited mitochondrial DNA (mtDNA), leading to impaired reproduction among males and lowered male effective population size. If correct, we should expect to see low levels of polymorphism in the male‐specific Y chromosome of many organisms but not necessarily in the female‐specific W chromosome in organisms with female (...) heterogamety. However, recent observations from birds suggest that the avian W chromosome is very low in nucleotide diversity. This indicates that mtDNA mutations cannot broadly explain the evolution of the sex‐limited chromosome. Other work has suggested that sexual selection at loci involved in sex determination or secondary sexual characteristics might reduce levels of genetic variability on Y through hitch‐hiking effects. Although the W chromosome does not seen to play a dominant role for sex determination in birds, it cannot be excluded that selective sweeps arising from natural or sexual selection contribute to the low levels of genetic variability seen on this chromosome. BioEssays 25:163–167, 2003. © 2003 Wiley Periodicals, Inc. (shrink)

Comparative mapping and sequencing show that turnover of sex determining genes and chromosomes, and sex chromosome rearrangements, accompany speciation in many vertebrates. Here I review the evidence and propose that the evolution of therian mammals was precipitated by evolution of the male‐determining SRY gene, defining a novel XY sex chromosome pair, and interposing a reproductive barrier with the ancestral population of synapsid reptiles 190 million years ago (MYA). Divergence was reinforced by multiple translocations in monotreme sex chromosomes, the (...) first of which supplied a novel sex determining gene. A sex chromosome‐autosome fusion may have separated eutherians (placental mammals) from marsupials 160 MYA. Another burst of sex chromosome change and speciation is occurring in rodents, precipitated by the degradation of the Y. And although primates have a more stable Y chromosome, it may be just a matter of time before the same fate overtakes our own lineage. (shrink)

Mammal sex determination depends on an XY chromosome system, a gene for testis development and a means of activating the X chromosome. The duckbill platypus challenges these dogmas.1,2 Gutzner et al.1 find no recognizable SRY sequence and question whether the mammalian X was even the original sex chromosome in the platypus. Instead they suggest that the original platypus sex chromosomes were derived from the ZW chromosome system of birds and reptiles. Unraveling the puzzles of sex determination (...) and dosage compensation in the platypus has been complicated by the fact that it has a surplus of sex chromosomes. Rather than a single X and Y chromosome, the male platypus has five Xs and five Ys. BioEssays 27:681–684, 2005. © 2005 Wiley Periodicals, Inc. (shrink)

In recent years, a great deal of evidence has accumulated on the health risks and environmental impacts of some herbicides. Both conventional agriculture and agroecology are searching for alternatives to address the challenges posed by the consequences of herbicide use. In this search, peasant and indigenous agroecosystems have much to contribute since their crops evolved thousands of years ago together with diverse communities of weeds, and farmers have carried out sophisticated strategies to manage them. Through participant observation, semi-structured interviews, free (...) lists, and botanical collection, we document a milpa design that integrates and manages spontaneous vegetation to take advantage of its presence and minimize risks of crop loss. The objective of this article is to critically contrast agroecological mechanisms in this milpa design which matches the prevention principle with a set of recommendations recognized as preventive in conventional weed science. (shrink)

BackgroundBioethics and law distinguish between the practices of "physician-assisted death" and "allowing the patient to die."DiscussionAdvances in biotechnology have allowed medical devices to be used as destination therapy that are designed for the permanent support of cardiac function and/or respiration after irreversible loss of these spontaneous vital functions. For permanent support of cardiac function, single ventricle or biventricular mechanical assist devices and total artificial hearts are implanted in the body. Mechanical ventilators extrinsic to the body are used for permanent (...) support of respiration. Clinical studies have shown that destination therapy with ventricular assist devices improves patient survival compared to medical management, but at the cost of a substantial alteration in end-of-life trajectories. The moral and legal assessment of the appropriateness and permissibility of complying with a patient's request to electively discontinue destination therapy in a life-terminating act in non-futile situations has generated controversy. Some argue that complying with this request is ethically justified because patients have the right to request withdrawal of unwanted treatment and be allowed to die of preexisting disease. Other commentators reject the argument that acceding to an elective request for death by discontinuing destination therapy is 'allowing a patient to die' because of serious flaws in interpreting the intention, causation, and moral responsibility of the ensuing death.SummaryDestination therapy with cardiac and/or ventilatory medical devices replaces native physiological functions and successfully treats a preexisting disease. We posit that discontinuing cardiac and/or ventilatory support at the request of a patient or surrogate can be viewed as allowing the patient to die if--and only if--concurrent lethal pathophysiological conditions are present that are unrelated to those functions already supported by medical devices in destination therapy. In all other cases, compliance with a patient's request constitutes physician-assisted death because of the pathophysiology induced by the turning off of these medical devices, as well as the intention, causation, and moral responsibility of the ensuing death. The distinction between allowing the patient to die and physician-assisted death is pivotal to the moral and legal status of elective requests for death by discontinuing destination cardiac and/or ventilatory medical devices in patients who are not imminently dying. This distinction also represents essential information that must be disclosed to patients and surrogates in advance of consent to this type of therapy. (shrink)

Chromosomes that harbor dominant sex determination loci are predicted to erode over time—losing genes, accumulating transposable elements, degenerating into a functional wasteland and ultimately becoming extinct. The Drosophila melanogaster Y chromosome is fairly far along this path to oblivion. The few genes on largely heterochromatic Y chromosome are required for spermatocyte‐specific functions, but have no role in other tissues. Surprisingly, a recent paper shows that divergent Y chromosomes can substantially influence gene expression throughout the D. melanogaster genome.1 These (...) results show that variation on Y has an important influence on the deployment of the genome. BioEssays 30:409–411, 2008. © 2008 Wiley Periodicals, Inc. (shrink)

Telomeres are protective caps for chromosome ends that are essential for genome stability. Broken chromosomes missing a telomere will not be maintained unless the chromosome is ‘healed’ with the formation of a new telomere. Chromosome healing can be a programmed event following developmentally regulated chromosome fragmentation, or it may occur spontaneously when a chromosome is accidentally broken. In this article we discuss the consequences of telomere loss and the possible mechanisms that the enzyme telomerase (...) employs to form telomeres de novo on broken chromosome ends. (shrink)

Telomeres play a vital role in protecting the ends of chromosomes and preventing chromosome fusion. The failure of cancer cells to properly maintain telomeres can be an important source of the chromosome instability involved in cancer cell progression. Telomere loss results in sister chromatid fusion and prolonged breakage/fusion/bridge (B/F/B) cycles, leading to extensive DNA amplification and large deletions. These B/F/B cycles end primarily when the unstable chromosome acquires a new telomere by translocation of the ends of (...) other chromosomes. Many of these translocations are nonreciprocal, resulting in the loss of the telomere from the donor chromosome, providing a mechanism for transfer of instability from one chromosome to another until a chromosome acquires a telomere by a mechanism other than nonreciprocal translocation. B/F/B cycles can also result in other forms of chromosome rearrangements, including double‐minute chromosomes and large duplications. Thus, the loss of a single telomere can result in instability in multiple chromosomes, and generate many of the types of rearrangements commonly associated with human cancer. BioEssays 26:1164–1174, 2004. © 2004 Wiley Periodicals, Inc. (shrink)

Graphical AbstractOn the Black Swans of conventional sex determination theory: There aren't many, but when an exception to the standard model of sex determination (evolutionary turnover of genes playing the role of “master sex determiner”) arises, it certainly screams out for an explanation. In this issue, a novel one is put forward. It now awaits testing, particularly at the population level.

Faithful DNA replication and accurate chromosome segregation are the key machineries of genetic transmission. Disruption of these processes represents a hallmark of cancer and often results from loss of tumor suppressors. PTEN is an important tumor suppressor that is frequently mutated or deleted in human cancer. Loss of PTEN has been associated with aneuploidy and poor prognosis in cancer patients. In mice, Pten deletion or mutation drives genomic instability and tumor development. PTEN deficiency induces DNA replication stress, (...) confers stress tolerance, and disrupts mitotic spindle architecture, leading to accumulation of structural and numerical chromosome instability. Therefore, PTEN guards the genome by controlling multiple processes of chromosome inheritance. Here, we summarize current understanding of the PTEN function in promoting high-fidelity transmission of genetic information. We also discuss the PTEN pathways of genome maintenance and highlight potential targets for cancer treatment. PTEN is a guardian of the genome. However, the role of PTEN in guarding the genome has not been revealed until recently. PTEN controls multiple fundamental processes of genomic transmission. By physically interacting with key molecules in DNA replication, DNA repair/decatenation, and chromosome segregation during the cell cycle, PTEN maintains genomicintegrity and fitness. (shrink)

In most discussions of the evolution of sex chromosomes, it is presumed that the morphological differences between the X and Y were initiated by genetic changes. An alternative possibility is that, in the early stages, a key role was played by epigenetic modifications of chromatin structure that did not depend directly on genetic changes. Such modifications could have resulted from spontaneous epimutations at a sex‐determining locus or, in mammals, from selection in females for the epigenetic silencing of imprinted regions of (...) the paternally derived sex chromosome. Other features of mammalian sex chromosomes that are easier to explain if the epigenetic dimension of chromosome evolution is considered include the relatively large number of X‐linked genes associated with human brain development, and the overrepresentation of spermatogenesis genes on the X. Both may be evolutionary consequences of dosage compensation through X‐inactivation. BioEssays 26:1327–1332, 2004. © 2004 Wiley Periodicals, Inc. (shrink)

Se examinan las diversas modalidades de la nada como casos de pérdida del sentido y falta de consumación del conocimiento: la nada como noúmeno y su relación con el fenómeno, así como la conexión trascendental de ambos. Aunque la nada pone en jaque al concepto de sentido, este se encuentra supuesto antes de todo tipo de pregunta por el ser, y se constituye en el trasfondo de las condiciones trascendentales que posibilitan el conocimiento. Various modes of non-being are examined as (...) cases of loss of sense and as a lack of consummation of knowledge: non-being as noumena and its relationship with the phenomena, as well as the transcendental connection between them. Although non-being makes the concept of sense doubtful, it is presupposed before any kind of question regarding being and it is constituted in the background which belongs to the transcendental conditions which make knowledge possible. (shrink)