Alzheimer's disease is characterized by plaques of amyloid-beta peptide, cleaved from amyloid-beta protein precursor . Our hypothesis is that lifespan profiles of AD-associated mRNA and protein levels in monkeys would differ from mice and that differential lifespan expression profiles would be useful to understand human AD pathogenesis. We compared profiles of AbetaPP mRNA, AbetaPP protein, and Abeta levels in rodents and primates. We also tracked a transcriptional regulator of the AbetaPP gene, specificity protein 1 , and the beta amyloid precursor (...) cleaving enzyme . In mice, AbetaPP and SP1 mRNA and their protein products were elevated late in life; Abeta levels declined in old age. In monkeys, SP1, AbetaPP, and BACE1 mRNA declined in old age, while protein products and Abeta levels rose. Proteolytic processing in both species did not match production of Abeta. In primates, AbetaPP and SP1 mRNA levels coordinate, but an inverse relationship exists with corresponding protein products as well as Abeta levels. Comparison of human DNA and mRNA sequences to monkey and mouse counterparts revealed structural features that may explain differences in transcriptional and translational processing. These findings are important for selecting appropriate models for AD and other age-related diseases. (shrink)

The sporadic nature of Alzheimer's disease argues for an environmental link that may drive AD pathogenesis; however, the triggering factors and the period of their action are unknown. Recent studies in rodents have shown that exposure to lead during brain development predetermined the expression and regulation of the amyloid precursor protein and its amyloidogenic beta-amyloid product in old age. Here, we report that the expression of AD-related genes [APP, BACE1 ] as well as their transcriptional regulator were elevated in aged (...) monkeys exposed to Pb as infants. Furthermore, developmental exposure to Pb altered the levels, characteristics, and intracellular distribution of Abeta staining and amyloid plaques in the frontal association cortex. These latent effects were accompanied by a decrease in DNA methyltransferase activity and higher levels of oxidative damage to DNA, indicating that epigenetic imprinting in early life influenced the expression of AD-related genes and promoted DNA damage and pathogenesis. These data suggest that AD pathogenesis is influenced by early life exposures and argue for both an environmental trigger and a developmental origin of AD. (shrink)

We recently synthesized and reinterpreted published studies to advance an epigenetic model for the development of homosexuality (HS). The model is based on epigenetic marks laid down in response to the XX vs. XY karyotype in embryonic stem cells. These marks boost sensitivity to testosterone in XY fetuses and lower it in XX fetuses, thereby canalizing sexual development. Our model predicts that a subset of these canalizing epigenetic marks stochastically carry over across generations and lead to mosaicism for sexual development (...) in opposite‐sex offspring – the homosexual phenotype being one such outcome. Here, we begin by outlining why HS has been under‐appreciated as a commonplace phenomenon in nature, and how this trend is currently being reversed in the field of neurobiology. We next briefly describe our epigenetic model of HS, develop a set of predictions, and describe how epigenetic profiles of human stem cells can provide for a strong test of the model. (shrink)

Successful formulation and implementation of end-of-life care requires ongoing communication with the patient. When patients, for reasons of general medical or psychiatric illness, fail to verbally communicate, providers must be receptive to messages conveyed through alternate avenues of communication. We present the narrative of a man with schizophrenia who wished to forgo hemodialysis as a study in the ethical importance of attention to nonverbal communication. A multilayered understanding of the patient, as may be provided by both behavioral and motivational models, (...) can inform the provider’s ability to receive, process, and represent communicated content to the patient or his or her surrogate decision-maker. (shrink)

Alzheimer's disease is characterized by amyloid-beta peptide -loaded plaques in the brain. Abeta is a cleavage fragment of amyloid-beta protein precursor and over production of APP may lead to amyloidogenesis. The regulatory region of the APP gene contains consensus sites recognized by the transcription factor, specificity protein 1 , which has been shown to be required for the regulation of APP and Abeta. To understand the role of SP1 in APP biogenesis, herein we have characterized the relative distribution and localization (...) of SP1, APP, and Abeta in various brain regions of rodent and primate models using immunohistochemistry. We observed that overall distribution and cellular localization of SP1, APP, and Abeta are similar and neuronal in origin. Their distribution is abundant in various layers of neocortex, but restricted to the Purkinje cell layer of the cerebellum, and the pyramidal cell layer of hippocampus. These findings suggest that overproduction of Abeta in vivo may be associated with transcriptional pathways involving SP1 and the APP gene. (shrink)

The focus of this study was to analyze the content, distribution, and comparative genome relationships of 996 chromosome bin-mapped expressed sequence tags accounting for 2266 restriction fragments on the homoeologous group 3 chromosomes of hexaploid wheat. Of these loci, 634, 884, and 748 were mapped on chromosomes 3A, 3B, and 3D, respectively. The individual chromosome bin maps revealed bins with a high density of mapped ESTs in the distal region and bins of low density in the proximal region of the (...) chromosome arms, with the exception of 3DS and 3DL. These distributions were more localized on the higher-resolution group 3 consensus map with intermediate regions of high-mapped-EST density on both chromosome arms. Gene ontology classification of mapped ESTs was not significantly different for homoeologous group 3 chromosomes compared to the other groups. A combined analysis of the individual bin maps using 537 of the mapped ESTs revealed rearrangements between the group 3 chromosomes. Approximately 232 of the consensus mapped ESTs matched sequences on rice chromosome 1 and revealed large- and small-scale differences in gene order. Of the group 3 mapped EST unigenes ∼21 and 32% matched the Arabidopsis coding regions and proteins, respectively, but no chromosome-level gene order conservation was detected. (shrink)

Codex Louaniensis, or L, the best MS. of Caesar in the British Museum , which is assigned to the eleventh century, has been collated by Alfred Holder for his edition of the Bellum ciuile and by Mr. R. L. A. Du Pontet for his edition of the Bellum Alexandrinum and the Bellum Africanum; but for the Bellum Gallicum no collation has hitherto been available. Last year I made one, which I sent to Dr. Meusel. He urged me to publish it, (...) remarking that it would be very useful, as ‘wir haben nun ein sichereres Urteil über die Familie φ.’ Relying upon Holder's collation, he had described L in his own edition of the Bellum ciuile as ‘a twin-brother of Ashburnhamianus’ ; and so it is in the Bellum ciuile, but, as he acknowledged after reading my collation, not in the Bellum Gallicum. The first folio, comprising i, I–6, §3 , is by a later hand. The MS. is described in the Catalogue thus: ‘c. Jvlii Caesaris commentariorum libri. Desinit cum verbis “res eis suppeteret” in libro de Bello Africano, cap. 33. Codex membranaceus, sec. XL, sed folium primum a manu recentiori suppletum est. Folio [10,084.].’. (shrink)

The complex hexaploid wheat genome offers many challenges for genomics research. Expressed sequence tags facilitate the analysis of gene-coding regions and provide a rich source of molecular markers for mapping and comparison with model organisms. The objectives of this study were to construct a high-density EST chromosome bin map of wheat homoeologous group 2 chromosomes to determine the distribution of ESTs, construct a consensus map of group 2 ESTs, investigate synteny, examine patterns of duplication, and assess the colinearity with (...) class='Hi'>rice of ESTs assigned to the group 2 consensus bin map. A total of 2600 loci generated from 1110 ESTs were mapped to group 2 chromosomes by Southern hybridization onto wheat aneuploid chromosome and deletion stocks. A consensus map was constructed of 552 ESTs mapping to more than one group 2 chromosome. Regions of high gene density in distal bins and low gene density in proximal bins were found. Two interstitial gene-rich islands flanked by relatively gene-poor regions on both the short and long arms and having good synteny with rice were discovered. The map locations of two ESTs indicated the possible presence of a small pericentric inversion on chromosome 2B. Wheat chromosome group 2 was shown to share syntenous blocks with rice chromosomes 4 and 7. (shrink)

The Role of Dorsal Premotor Cortex in Resolving Abstract Motor Rules provides alternative hypotheses about the cognitive functions affected by the application of repetitive transcranial magnetic stimulation. Their model simulated the effect of stimulation of the left dorsal premotor cortex right as participants provide a Models were used to demonstrate that the increased variability in observed response times can result from interference in replanning during the process of responding to the uninstructed stimulus.

A total of 944 expressed sequence tags generated 2212 EST loci mapped to homoeologous group 1 chromosomes in hexaploid wheat. EST deletion maps and the consensus map of group 1 chromosomes were constructed to show EST distribution. EST loci were unevenly distributed among chromosomes 1A, 1B, and ID with 660, 826, and 726, respectively. The number of EST loci was greater on the long arms than on the short arms for all three chromosomes. The distribution of ESTs along chromosome arms (...) was nonrandom with EST clusters occurring in the distal regions of short arms and middle regions of long arms. Duplications of group 1 ESTs in other homoeologous groups occurred at a rate of 35.5%. Seventy-five percent of wheat chromosome 1 ESTs had significant matches with rice sequences, where large regions of conservation occurred between wheat consensus chromosome 1 and rice chromosome 5 and between the proximal portion of the long arm of wheat consensus chromosome 1 and rice chromosome 10. Only 9.5% of group 1 ESTs showed significant matches to Arabidopsis genome sequences. The results presented are useful for gene mapping and evolutionary and comparative genomics of grasses. (shrink)

We study the relationship between a computably enumerable real and its presentations. A set A presents a computably enumerable real α if A is a computably enumerable prefix-free set of strings such that equation image. Note that equation image is precisely the measure of the set of reals that have a string in A as an initial segment. So we will simply abbreviate equation image by μ. It is known that whenever A so presents α then A ≤wttα, where ≤wtt (...) denotes weak truth table reducibility, and that the wtt-degrees of presentations form an ideal ℐ in the computably enumerable wtt-degrees. We prove that any such ideal is equation image, and conversely that if ℐ is any nonempty equation image ideal in the computably enumerable wtt-degrees then there is a computable enumerable real α such that ℐ = ℐ. We also prove a kind of Rice Theorem for these ideals, namely that if the index set of such a equation image ideal is not empty or equal to ω then it is equation image-complete. (shrink)

Rice crop diversity hasdecreased dramatically in the recent past.Understanding the causes that underlie theevident genetic erosion is critical for thefood security of subsistence rice farmers andbiodiversity. Our study shows that farmers inthe northeastern Philippines had a markedreduction in rice diversity from 1996 to 1998.The ultimate causes were a drought resultingfrom the El Niño phenomenon in 1997 andflooding due to two successive typhoons in1998. The proximate causes, however, includedlocal water control factors, limitations in thehousehold and village-level seedinfrastructure, farm (...) location in relation tothe goods and services necessary to obtainseeds, policies and programs of the Departmentof Agriculture, and the characteristics of therice varieties themselves. The implications ofour study are that genetic erosion is notalways the result of purposeful acts by farmersnor is it necessarily gradual. Improvingon-farm seed technology will stabilize the seedproduction, distribution, and use system andthereby enhance household food security.Ultimately, rice diversity will be improvedonly if diversity is a safe and viable optionfor farmers. Therefore, public policy thatsupports farmers who maintain a diverse set ofcultivars is critical for any on-farmconservation strategy. (shrink)

The objectives of this study were to develop a high-density chromosome bin map of homoeologous group 7 in hexaploid wheat, to identify gene distribution in these chromosomes, and to perform comparative studies of wheat with rice and barley. We mapped 2148 loci from 919 EST clones onto group 7 chromosomes of wheat. In the majority of cases the numbers of loci were significantly lower in the centromeric regions and tended to increase in the distal regions. The level of duplicated (...) loci in this group was 24% with most of these loci being localized toward the distal regions. One hundred nineteen EST probes that hybridized to three fragments and mapped to the three group 7 chromosomes were designated landmark probes and were used to construct a consensus homoeologous group 7 map. An additional 49 probes that mapped to 7AS, 7DS, and the ancestral translocated segment involving 7BS also were designated landmarks. Landmark probe orders and comparative maps of wheat, rice, and barley were produced on the basis of corresponding rice BAC/PAC and genetic markers that mapped on chromosomes 6 and 8 of rice. Identification of landmark ESTs and development of consensus maps may provide a framework of conserved coding regions predating the evolution of wheat genomes. (shrink)

A total of 1918 loci, detected by the hybridization of 938 expressed sequence tag unigenes from 26 Triticeae cDNA libraries, were mapped to wheat homoeologous group 4 chromosomes using a set of deletion, ditelosomic, and nulli-tetrasomic lines. The 1918 EST loci were not distributed uniformly among the three group 4 chromosomes; 41, 28, and 31% mapped to chromosomes 4A, 4B, and 4D, respectively. This pattern is in contrast to the cumulative results of EST mapping in all homoeologous groups, as reported (...) elsewhere, that found the highest proportion of loci mapped to the B genome. Sixty-five percent of these 1918 loci mapped to the long arms of homoeologous group 4 chromosomes, while 35% mapped to the short arms. The distal regions of chromosome arms showed higher numbers of loci than the proximal regions, with the exception of 4DL. This study confirmed the complex structure of chromosome 4A that contains two reciprocal translocations and two inversions, previously identified. An additional inversion in the centromeric region of 4A was revealed. A consensus map for homoeologous group 4 was developed from 119 ESTs unique to group 4. Forty-nine percent of these ESTs were found to be homoologous to sequences on rice chromosome 3, 12% had matches with sequences on other rice chromosomes, and 39% had no matches with rice sequences at all. Limited homology was found between wheat ESTs on homoeologous group 4 and the Arabidopsis genome. Forty-two percent of the homoeologous group 4 ESTs could be classified into functional categories on the basis of blastX searches against all protein databases. (shrink)

In this article, we use the theory of Information Ethics to argue that deceased people have a prima facie moral right to privacy in the context of health data research, and that this should be reflected in regulation and guidelines. After death, people are no longer biological subjects but continue to exist as informational entities which can still be harmed/damaged. We find that while the instrumental value of recognising post-mortem privacy lies in the preservation of the social contract for health (...) research, its intrinsic value is grounded in respect for the dignity of the post-mortem informational entity. However, existing guidance on post-mortem data protection is available only in the context of genetic studies. In comparing the characteristics of genetic data and other health-related data, we identify two features of DNA often given as arguments for this genetic exceptionalism: relationality and embodiment. We use these concepts to show that at the appropriate Level of Abstraction, there is no morally relevant distinction between posthumous genetic and other health data. Thus, genetic data should not automatically receive special moral status after death. Instead we make a plea for ‘contextual exceptionalism’. Our analysis concludes by reflecting on a real-world case and providing suggestions for contextual factors that researchers and oversight bodies should take into account when designing and evaluating research projects with health data from deceased subjects. (shrink)

A central question of this chapter is how we can relate the unique ethos of Japan to the ways that influences of international bioethics, civil rights and legal reforms have shifted medical research in Japan from the legacy of the structured paternalism and impunity that allowed abuses to be committed by medical researchers in the World War II era, including in Unit 731 and in medical schools in Japan, to contemporary research agendas and policies. Throughout the twentieth century, Japan has (...) been a centre of research and innovation. The pro-technology attitudes still exist in current Japan, with the evolution of bioethics. Although we can trace the origins of bioethics in Japan back through millennia, with the Ainu indigenous practices and relationships to nature, the sophisticated hierarchical relationships expressed in the seventh century A.D. book the Kojiki, the conversion of forest to rice paddies, emergence of an integrated religious system including Shintoism and Buddhism, and the sophisticated class system supported by linguistics and social relationships, this chapter would argue that one of the most influential influence for this question is the Samurai tradition. This tradition values both autonomy and informed choice, while also allowing the legacy of tolerance of the elite classes to make decisions that may sacrifice some persons for the greater good. While principles of solidarity and social justice are a solid basis for universal health insurance they also allow sacrifices when necessary. Informed consent is now widely accepted, and bioethics is part of a transition which is transforming Japanese society from a paternalistic society to an individualistic one. Among the issues that will be used to illustrate the situation, are the functioning of research ethics committees, large gene bank and epidemiological projects, organ transplantation, truth telling, euthanasia and the public health measures such as mask wearing in the current COIVD-19 pandemic. (shrink)

This study examined self-reported academic dishonesty at a midsize public university. Students (N = 492) rated the likelihood they would cheat after accepting to abide by each of eight honor code pledges before Internet-based assignments and examinations. The statements were derived from honor pledges used by different universities across the United States and varied in length, formality, and the extent to which the statements included consequences for academic dishonesty. Longer, formal honor codes with consequences were associated with a lower likelihood (...) to cheat. Results showed a significant three-way interaction and suggest how to best design honor codes. (shrink)

Organ availability for transplantation has become an increasingly complex and difficult question in health economics and ethical practice. Advances in technology have seen prolonged life expectancy, and the global push for organs creates an ever-expanding gap between supply and demand, and a significant cost in bridging that gap. This article will examine the ethical implications for the nursing profession in regard to the procurement of organs from an impoverished seller’s market, also known as ‘Transplant Tourism’. This ethical dilemma concerns itself (...) with resource allocation, informed consent and the concepts of egalitarianism and libertarianism. Transplant Tourism is an unacceptable trespass against human dignity and rights from both a nursing and collective viewpoint. Currently, the Australian Nursing and Midwifery Council, the Royal college of Nursing Australia, The Royal College of Nursing (UK) and the American Nurses Association do not have position statements on transplant tourism, and this diminishes us as a force for change. It diminishes our role as advocates for the most marginalised in our world to have access to care and to choice and excludes us from a very contemporary real debate about the mismatch of organ demand and supply in our own communities. As a profession, we must have a voice in health policy and human rights, and according to our Code of Ethics in Australia and around the world, act to promote and protect the fundamental human right to healthcare and dignity. (shrink)

This book of fifteen essays is presented in honor of one of the premier historians of medieval philosophy, Armand Maurer of the Pontifical Institute for Mediaeval Studies and the University of Toronto. The authors, internationally recognized scholars in the field of medieval philosophy and theology, are friends, colleagues, and students of Fr. Maurer. They are united in a common love of medieval thought and a common appreciation of philosophizing through the study of the history of philosophy. Their interests and methodologies, (...) however, are diverse, and cover a range from Justin Marytr, who died during the reign of Marcus Aurelius, to Bartholomew Mastrius, a contemporary of Descartes. “This is a volume that honors the memory of Armand Maurer not only by reviewing his own scholarly achievements but by advancing the state of scholarship on the subject that he loved, the philosophy of the middle ages. The range of topics covered here richly reflect the pluralism of medieval thought. Some of the essays gathered for this collection give a fresh look at important perennial themes like the nature of Christian philosophy and the real distinction between essence and existence. Others turn—as Maurer loved to do—to figures who are studied less often that help fill out our knowledge of this period and add to our sense of the contributions that study of medieval authors can make for contemporary philosophizing.” —Joseph W. Koterski, S.J., Fordham University “This lovely Festschrift for Armand Maurer contains fourteen essays by distinguished scholars on the tradition of medieval philosophy, from its ancient origins to seventeenth-century inheritors. Since many essays treat large-scale movements or fundamental issues, the volume will be useful to serious undergraduates and graduate students, as well as to scholars._ Laudemus_ indeed: from the editor’s moving tribute to Armand Maurer, through discussions of Avicenna and Thomas and Ockham, to Maurer’s closing recollections of his teachers, this volume is full of well-earned praise.” —Donald Morrison, Rice University. (shrink)

To localize wheat ESTs on chromosomes, 882 homoeologous group 6-specific ESTs were identified by physically mapping 7965 singletons from 37 cDNA libraries on 146 chromosome, arm, and sub-arm aneuploid and deletion stocks. The 882 ESTs were physically mapped to 25 regions flanked by 23 deletion breakpoints. Of the 5154 restriction fragments detected by 882 ESTs, 2043 were localized to group 6 chromosomes and 806 were mapped on other chromosome groups. The number of loci mapped was greatest on chromosome 6B and (...) least on 6D. The 264 ESTs that detected orthologous loci on all three homoeologs using one restriction enzyme were used to construct a consensus physical map. The physical distribution of ESTs was uneven on chromosomes with a tendency toward higher densities in the distal halves of chromosome arms. About 43% of the wheat group 6 ESTs identified rice homologs upon comparisons of genome sequences. Fifty-eight percent of these ESTs were present on rice chromosome 2 and the remaining were on other rice chromosomes. Even within the group 6 bins, rice chromosomal blocks identified by 1-6 wheat ESTs were homologous to up to 11 rice chromosomes. These rice-block contigs were used to resolve the order of wheat ESTs within each bin. (shrink)

Contractualism conceives of firm-stakeholder relations as cooperative schemes for mutual benefit. In essence, contractualism holds that these schemes, as well as the normative principles that guide and constrain them, are ultimately ratified by the consent and endorsement of those subject to them. This paper explores the empirical validity of a contractualist perspective on firm-stakeholder relations. It first develops a typology of firm-stakeholder contracting problems. It subsequently confronts this typology with empirical data collected in an interview study of concrete stakeholder management (...) practices, involving in-depth research interviews with forty-four managers working in the Dutch financial services industry. The findings of this theory-building study suggest that there are limits to the applicability of the contract model in the context of stakeholder management, and that disregarding either the model or its limitations may lead to highly ineffective firm-stakeholder relations. (shrink)

This paper describes a role for rural sociology in linking agrifood system vulnerabilities to opportunities for encouraging sustainability and social justice. I argue that the California rice industry is particularly vulnerable for two reasons. First, a quarter of rice growers’ revenues derive from production-based subsidies that have been recently deemed illegal by the World Trade Organization. Second, about half of California’s rice sales depend on volatile export markets, which are susceptible to periodic market access disruptions. Such vulnerabilities (...) present political opportunities to reconfigure the connection between production and consumption. By exploring how production subsidies could be transformed into multifunctionality payments, and investigating new regional markets, rural sociology can contribute to discussions about how to encourage a more sustainable and socially just California rice industry. My discussion aims to prompt rural sociologists to explore similar questions in comparable agrifood systems. (shrink)

Human resources are an evitable resource for achieving organizational goals. Human resources are no longer merely a factor of production but now play a crucial role in successful organizations. Every employee represents a bouquet of Competencies or talent. Many organizations view Human Resource Management as Talent Management. This study examines the relationship between talent analytics and employee retention. Talent analytics encompasses the processes, strategies, and technologies used to manage HR operations in an organization. Talent Analytics encompasses data-driven decision-making and analysis. (...) Attrition among workers is the opposite of employee retention. Talent Analytics may favourably impact several aspects of Talent Management, including recruitment, training, retention, career promotion, and redeployment. solutions. Many organisations can use historical data to forecast future outcomes. Employees who frequently visit job sites are more likely to leave the organisation for better opportunities. An employee with a large number of unresolved professional grievances may depart the organisation. Over 250 employees in the industrial sector provided feedback on the use of Talent Analytics. All of these responders are from Chennai. Data research revealed that most respondents believe Talent Analytics improves employee retention. The researcher investigated the relationship between the availability of a Talent Analytics System in a respondent's organisation and their intention to stay. (shrink)

Taking away grains from a heap of rice, at what point is there no longer a heap? It seems small changes – removing a single grain – can’t make a difference to whether or not something is a heap; but big changes obviously do. How can this be, since big changes are nothing but small changes chained together?