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)

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)

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)

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 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)

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)

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.

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)

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)

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)

There appears to be a wide measure of agreement, both amongst biologists and others, that Darwin's theory of evolution marks a major breakthrough in the science of biology; Darwin has even been called ‘Biology's Newton’, the highest term of praise that could be bestowed on a scientist. A. G. N. Flew, considering the matter from a philosophical point of view, says: ‘Yet one of the most important of all scientific theories is that developed by Darwin in his Origin of Species (...) . Covering the entire range of biological phenomena its scope is enormous. While if any scientific theory is interesting philosophically this one is.’ In spite of the testimony of both biologists and philosophers of science to the importance of the theory, it does not appear to play anything like the same role in biology as does Newton's theory in physics. For modern physics would be. (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)

'The ethical landscape', the title given to part of a course devised by Mr. Moore, is described in full in this paper. The whole course is a new adventure in medical education designed to help students to explore the ethical problems in the practice of medicine. The 'ethical landscape' is seen through discussion based on passages from literature depicting doctors' and patients' dilemmas. As the results summarized in the tables show, the students found the course well worth while, and thought (...) that they had gained a new insight into the problems with which they would be confronted and also into their own personalities and those of their fellow students whom previously they had only known superficially. The Chairman of the course, Mr. Moore, was also subjected to assessment from his students, because on the skill of the Chairman such a course would fail or succeed. (shrink)

Purpose This study aims to explore the association between internet addiction and problem behaviours on social networking sites using the general strain theory. Design/methodology/approach Using the purposive sampling method, a survey was conducted, which collected data from 414 college students studying in two public universities in South Australia. The Delphi method was used to develop the questionnaire used for the survey. Findings 'Results of this research indicated a significant association between internet addiction and problem behaviours on SNS. Respondents who had (...) engaged in problem behaviours on SNS had high internet addiction test scores. On the basis of this finding, the present research argues that the general strains associated with the suffering of newly emerging challenges such as internet addiction might contribute to victimisation and deviant and problem behaviours on SNS in specific and possibly in cyberspace in general. Research limitations/implications Results of the present study need to be interpreted cautiously due to many limitations it has. This research is a cross-sectional study, which might not adequately explain the associations between internet addiction and problem behaviours on SNS. Longitudinal studies involving larger samples might have added significant value to this study. The present study uses purposive sampling technique, which has limited its generalizability, and its findings may not be generalised to large populations. Originality/value Limited information is available pertaining to the association between problem behaviours on SNS and internet addiction. The present study is a pioneering effort, which argues that rapid popularity of SNS is likely to increase internet addiction and the frustration of not getting proper treatment for their internet addiction might lead to deviant behaviours on SNS. (shrink)

A law, say, prohibits homosexual conduct or punishes the prostitute for plying her trade. According to some it is a bad law, according to others a necessary one. Those who argue that it is a bad law do so on a variety of grounds—that it is sheer folly to try to change human nature by law, that such legislation can only be effective at the price of the right to privacy, that the punishment of acts arising from compelling desires is (...) cruel and excessive, that the law has no business meddling in what people do to others with their consent. Those who argue that it is a necessary law do so on one ground, that the act in question is immoral, and that what is wrong must be punished, lest the law itself fall into disrepute by failing to carry out a consistent campaign against wrong-doing. (shrink)

In this paper I want to examine the notion of desert, which seems to have been neglected by contemporary philosophers. Apartfrom its interest in its own right, it is important to be clear about the meaning of the word if there is to be any understanding of the idea of punishment. And that we are confused over the whole issue of punishment is obvious both from the remarks of professional philosophers and from the comments of the ‘man in the street’. (...) Because of this confusion, the discussion of any actual punishment seems to take place between two parties who never get to grips with the arguments of the other, as in the whole debate over the death penalty. To one set of people, it is obvious that the retention of hanging depends to a large extent on the question of its effectiveness in deterring murderers; to another it is equally obvious that the murderer ‘deserves’ to hang, and that there is no more to be said about the matter. Capital punishment is not a good starting-point for a discussion of punishment in general, for death is clearly unique among penalties; in addition, the topic gives rise inevitably to much sentimentality and resulting muddle-headedness. (shrink)

In this paper we conduct an analysis of the critical narratives of Stardew Valley and compare them to other relevant videogames in order to develop new possibilities for an ecological critique of capitalist extractive econo­mies. Critical narratives of this game are aimed primarily at the alienating conditions of labour and deeply devastating modes of production under capitalism that impact and severely damage the environment. Analysing these narratives, we superimpose the immediate messages of the game with the procedural rhetoric and material (...) conditions of their existence. Over the course of our analysis, we highlight a material-narrative disso­nance which, in the case of Stardew Valley, fails to function as a commu­nicative strategy of the game and remains its mere external contradiction. Although the game’s critical narrative may seem overly utopian and its political imaginary a bit underdeveloped, the game elaborates on concrete ways to tackle the alienation of labour and resolve the ecological crisis. In addition to this, the paper covers the history of the interplay between the video game industry and the field of global ecological crisis research. We compare the attempts to raise awareness of the videogames’ own material­ity that preceded Stardew Valley. We conclude that Stardew Valley utilises the language of sustainable co-existence and wasteless local production, expanding this logic both to the sphere of labour and the spectrum of en­vironmental problems. In the case of ecological critique, some gameplay decisions in Stardew Valley enable us to come up with new strategies aimed at creating critical narratives about the environment in videogames. Thus supplementing Stardew Valley’s findings with critical tropes derived from other games (mainly, Rain World), we were able to gather a set of theoretical instruments that could facilitate the creation of games about ecosystems. Following Donna Haraway’s emphasis on the crucial role of narrative fram­ing (“it matters which stories tell stories”), we highlight new opportunities for the entire medium of videogames. (shrink)

In their rare comments on Existentialism, contemporary British philosophers, with a few notable exceptions, frequently ridicule the use of “nothing” by such writers as Sartre and Heidegger. And when it is discovered that these writers maintain that the contemplation of nothingness gives rise to anguish, this ridicule is expressed even more strongly. What may be taken as a typical example of this tendency are Professor Ayer's remarks in his Horizon articles on Sartre. A characteristic quotation runs as follows: “In particular, (...) Sartre's reasoning on the subject of le néant seems to me exactly on a par with that of the King in Alice through the Looking-Glass … The point is that words like ‘nothing” and ‘nobody” are not used as the names of something insubstantial and mysterious; they are not used to name anything at all”;. (shrink)

In their rare comments on Existentialism, contemporary British philosophers, with a few notable exceptions, frequently ridicule the use of “nothing” by such writers as Sartre and Heidegger. And when it is discovered that these writers maintain that the contemplation of nothingness gives rise to anguish, this ridicule is expressed even more strongly. What may be taken as a typical example of this tendency are Professor Ayer's remarks in his Horizon articles on Sartre. A characteristic quotation runs as follows: “In particular, (...) Sartre's reasoning on the subject of le néant seems to me exactly on a par with that of the King in Alice through the Looking-Glass … The point is that words like ‘nothing” and ‘nobody” are not used as the names of something insubstantial and mysterious; they are not used to name anything at all”;. (shrink)

Utilitarianism has been attacked many times and from many points of view. Among other objections has been the charge that it cannot account for the moral phenomena connected with justice; we are interested, it is said, not only in producing as much good as possible, but also in distributing it in a certain way. The Utilitarian usually replies that these phenomena either can be deduced from Utilitarianism or are illusory, but a natural reluctance to go against the data of our (...) moral experience usually inclines him to the first alternative. One of the most interesting of the Utilitarians from this point of view is Sidgwick, because he makes Utilitarianism his philosophical basis, but at the same time he has a set of maxims 2 part of whose purpose is to cover the common-sense views on justice. In this article I shall consider the relations between these maxims and Utilitarianism, and shall try to show by means of an example that some of them do go beyond Utilitarianism, and that in so far, at any rate, as these maxims do represent the common-sense view, it and Utilitarianism are not in all cases strictly reconcilable. (shrink)