Effects of passage history and sampling bias on phylogenetic reconstruction of human influenza A evolution

In this paper we determine the extent to which host-mediated mutations and a known sampling bias affect evolutionary studies of human influenza A. Previous phylogenetic reconstruction of influenza A (H3N2) evolution using the hemagglutinin gene revealed an excess of nonsilent substitutions assigned to the terminal branches of the tree. We investigate two hypotheses to explain this observation. The first hypothesis is that the excess reflects mutations that were either not present or were at low frequency in the viral sample isolated from its human host, and that these mutations increased in frequency during passage of the virus in embryonated eggs. A set of 22 codons known to undergo such “host-mediated” mutations showed a significant excess of mutations assigned to branches attaching sequences from egg-cultured (as opposed to cell-cultured) isolates to the tree. Our second hypothesis is that the remaining excess results from sampling bias. Influenza surveillance is purposefully biased toward sequencing antigenically dissimilar strains in an effort to identify new variants that may signal the need to update the vaccine. This bias produces an excess of mutations assigned to terminal branches simply because an isolate with no close relatives is by definition attached to the tree by a relatively long branch. Simulations show that the magnitude of excess mutations we observed in the hemagglutinin tree is consistent with expectations based on our sampling protocol. Sampling bias does not affect inferences about evolution drawn from phylogenetic analyses. However, if possible, the excess caused by host-mediated mutations should be removed from studies of the evolution of influenza viruses as they replicate in their human hosts.

Clues to epidermal cancer proneness revealed by reconstruction of DNA repair-deficient xeroderma pigmentosum skin in vitro

Sun exposure has been clearly implicated in premature skin aging and neoplastic development. These features are exacerbated in patients with xeroderma pigmentosum (XP), a hereditary disease, the biochemical hallmark of which is a severe deficiency in the nucleotide excision repair of UV-induced DNA lesions. To develop an organotypic model of DNA repair deficiency, we have cultured several strains of primary XP keratinocytes and XP fibroblasts from skin biopsies of XP patients. XP skin comprising both a full-thickness epidermis and a dermal equivalent was succesfully reconstructed in vitro. Satisfactory features of stratification were obtained, but the expression of epidermal differentiation products, such as keratin K10 and loricrin, was delayed and reduced. In addition, the proliferation of XP keratinocytes was more rapid than that of normal keratinocytes. Moreover, increased deposition of cell attachment proteins, α-6 and β-1 integrins, was observed in the basement membrane zone, and β-1 integrin subunit, the expression of which is normally confined to basal keratinocytes, extended into several suprabasal cell layers. Most strikingly, the in vitro reconstructed XP skin displayed numerous proliferative epidermal invasions within dermal equivalents. Epidermal invasion and higher proliferation rate are reminiscent of early steps of neoplasia. Compared with normal skin, the DNA repair deficiency of in vitro reconstructed XP skin was documented by long-lasting persistence of UVB-induced DNA damage in all epidermal layers, including the basal layer from which carcinoma develops. The availability of in vitro reconstructed XP skin provides opportunities for research in the fields of photoaging, photocarcinogenesis, and tissue therapy.

Detecção e caracterização moleculares de Picobirnavirus bovino na região centro-sul do Brasil

Picobirnavirus (PBV) pertencem à família Picobirnaviridae, divididos em duas espécies Human Picobirnavirus e Rabbit Picobirnavirus. São pequenos vírus constituídos de genoma bissegmentado de cadeia dupla de RNA (dsRNA), não envelopados, com capsídeo de simetria icosaédrica, sendo divididos em dois genogrupos, GI e GII. Já foram detectados em fezes humanas e de uma ampla gama de espécies animais, com ou sem sinais diarreicos, sendo considerados agentes emergentes e oportunistas, e seu potencial zoonótico foi sugerido. Entretanto, os estudos epidemiológicos e moleculares de PBV em bovinos são raros na literatura nacional e internacional. Devido à carência de dados a respeito de PBV em bovinos, o presente estudo foi realizado objetivando-se a detecção e caracterização moleculares de cepas de PVB bovinos dos genogrupos GI e GII em amostras fecais de bovinos com ou sem sintomatologia diarreica de diferentes idades e regiões do Brasil. O estudo foi conduzido a partir de 77 animais, obtendo-se 18 (23,3%) amostras positivas para GI, compreendendo animais provenientes dos estados de São Paulo, Minas Gerais e Goiás. Não foram detectadas amostras positivas para GII. A identidade nucleotídica das amostras obtidas apresentou média de 67,4% quando comparadas uma com as outras e de até 83,77% quando comparadas com amostras de PBV de referência. Na reconstrução filogenética, três amostras agruparam-se em clado de PVB humano e somente uma agrupou-se em clado de PVB bovino. Em síntese, os resultados obtidos indicam, de maneira inédita, a circulação de PVB bovino pertencente ao genogrupo GI em diferentes estados brasileiros, com perfis filogenéticos heterogêneos.

Broadening the Scope of Ethnic Identity: A Social Sustainability Solution for Pan African Communities through Ethnically Relevant Educational Programming

This conceptual study explores ethnic identity development theory in order to argue that ethnic identity development education is a means of developing broad senses of community in the African Diaspora that expand beyond a tribal, local, familial level. This study suggests that the broadening of community understanding would contribute to establishing social sustainability on regional, national and international levels within the Pan African community. Establishing such social sustainability would have direct effects on the areas of economic and environmental sustainability. One of the goals of this project is to offer suggestions for ethnically relevant education that can develop social sustainability in several places throughout the Diaspora, such as in Nigeria where ethnic conflicts are a contemporary concern.

Le collectif contrarié : analyse des manifestations du sujet national et de sa remise en cause dans l'oeuvre de Robert Morin

La nation s’est affirmée à partir de la fin du 18e siècle comme l’un des grands paramètres de la modernité. Sa remise en cause, tout spécialement dans les dernières décennies du siècle dernier, est à la fois partie prenante et symptomatique de l’actuel phénomène d’effritement des identités collectives. Le Québec n’échappe pas à ce courant de fond, comme en témoigne l’œuvre du vidéaste et cinéaste Robert Morin, qui propose une galerie de personnages en manque d’attaches et souvent réduits à leur propre subjectivité. Dans un contexte de questionnement généralisé des concepts de nation et de collectivité, ces individualités se sentent isolées et tentent désespérément de réactualiser les liens qui les unissent à leurs semblables, mais sans grand succès. La communauté revêt ainsi une dimension nostalgique, parcourant l’œuvre de Morin dans son entièreté et se manifestant de différentes manières, tant à l’écran qu’à travers son approche du médium qui reste grandement tributaire des pratiques filmiques et vidéographiques des années ’60 et ’70. Écartelé entre la prise de conscience de son isolement et son désir d’appartenir à une entité collective, qu’elle soit nationale ou autre, le sujet délié que l’on retrouve chez Morin, comme cette thèse tente de le démontrer, subit ce phénomène de déliaison et lutte simultanément pour l’enrayer.

The Catholic Identity of Malta after Ten Years of Membership in the European Union: Challenges and Prospects. Occasional Paper 2/2014

Introduction. Ten years have elapsed since Malta’s accession in the European Union. One can still recall vividly the intense and acrimonious campaign prior to the membership referendum and the ensuing electoral victory that confirmed the Nationalist Party (PN) in power under the leadership of Edward Fenech Adami in 2003. In both cases the Maltese voted in favour of entry into the EU. During both exercises in democracy the Maltese were exposed to the rhetoric of both prophets of doom and prophets of plenty. For the former accession meant a loss of national and territorial independence, for the latter it meant the beginning of opportunity for all and, in some cases, the answer to all of Malta’s woes. Now, ten years later, a further appraisal of Malta’s membership and place in the European Union is called for. The purpose of this paper, however, is to reflect upon how this membership has affected the Roman Catholic Church in Malta and what prospects lie ahead for the Catholic community within Maltese society that remains in a state of constant flux on both the social and the religious level. It traces the major events that have accelerated the transformation of Malta into a secular society. The paper describes how these events, together with pressures that are being brought to bear by secular movements upon Maltese society, are profoundly affecting its Catholic identity and redrawing its moral landscape. It also discusses ways and means by which the Catholic Church in Malta can address these challenges and contribute towards the construction of a more humane Maltese society. In order to achieve this, it must first and foremost remain a coherent witness of a faith that is forever alive, dynamic and relevant.

How European Integration Impacts on National Legislatures: The Europeanization of The German Bundestag. CES Germany and Europe Working Papers, No. 06.2, 2006

In looking at the Europeanization of the German Bundestag, the paper brings together two different debates: the well-established debate on the democratic legitimacy of the European Union sees national Parliaments as guarantor of one branch of a "dual" legitimacy. The more recent debate on "Europeanization" addresses the impacts that European integration has had on its Member States. Analyzing the Europeanization of the German Bundestag, the paper identifies and analyzes three dimensions: legislative Europeanization – the extent to which legislative decision making by the German Bundestag has been influenced by European stipulations over the last twenty years; institutional Europeanization – how the Bundestag as an institution reacted to this loss of function by establishing institutional and procedural provisions for influencing the government's Euro-politics; and strategic Europeanization – the ways in which individual MPs started more recently to develop euro-political strategies that go beyond controlling the national government. The paper shows that the Bundestag only hesitantly reacted to the increasing loss of functions through legislative Europeanization by establishing effective institutional and procedural provisions for controlling the government's Euro-political activities. What is more, the establishment of institutions does not guarantee their effective use. All in all, Euro- politics continues to remain the activity of few MPs. These few, however, have more recently started to europeanize their strategies. The empirical findings support the claim that the traditional concept of chains of legitimacy is inadequate, both in conceptual and in empirical terms. With regard to the democ- ratic legitimacy of EU governance, this indicates that, apart from major reform projects, especially with regard to everyday legislation, not too great a burden should be placed on national Parliaments.

A two-step mechanism for epigenetic specification of centromere identity and function

The basic determinant of chromosome inheritance, the centromere, is specified in many eukaryotes by an epigenetic mark. Using gene targeting in human cells and fission yeast, chromatin containing the centromere-specific histone H3 variant CENP-A is demonstrated to be the epigenetic mark that acts through a two-step mechanism to identify, maintain and propagate centromere function indefinitely. Initially, centromere position is replicated and maintained by chromatin assembled with the centromere-targeting domain (CATD) of CENP-A substituted into H3. Subsequently, nucleation of kinetochore assembly onto CATD-containing chromatin is shown to require either the amino- or carboxy-terminal tail of CENP-A for recruitment of inner kinetochore proteins, including stabilizing CENP-B binding to human centromeres or direct recruitment of CENP-C, respectively.

Le collectif contrarié : analyse des manifestations du sujet national et de sa remise en cause dans l'oeuvre de Robert Morin

La nation s’est affirmée à partir de la fin du 18e siècle comme l’un des grands paramètres de la modernité. Sa remise en cause, tout spécialement dans les dernières décennies du siècle dernier, est à la fois partie prenante et symptomatique de l’actuel phénomène d’effritement des identités collectives. Le Québec n’échappe pas à ce courant de fond, comme en témoigne l’œuvre du vidéaste et cinéaste Robert Morin, qui propose une galerie de personnages en manque d’attaches et souvent réduits à leur propre subjectivité. Dans un contexte de questionnement généralisé des concepts de nation et de collectivité, ces individualités se sentent isolées et tentent désespérément de réactualiser les liens qui les unissent à leurs semblables, mais sans grand succès. La communauté revêt ainsi une dimension nostalgique, parcourant l’œuvre de Morin dans son entièreté et se manifestant de différentes manières, tant à l’écran qu’à travers son approche du médium qui reste grandement tributaire des pratiques filmiques et vidéographiques des années ’60 et ’70. Écartelé entre la prise de conscience de son isolement et son désir d’appartenir à une entité collective, qu’elle soit nationale ou autre, le sujet délié que l’on retrouve chez Morin, comme cette thèse tente de le démontrer, subit ce phénomène de déliaison et lutte simultanément pour l’enrayer.

Age determination and Sea surface temperature reconstruction for sediment core H214

We present sea surface temperature (SST) records with centennial-scale resolution from the Bay of Plenty, north of New Zealand. Foraminiferal assemblage-based paleo-SST estimates provide a deglacial record of SST since 16.5 14C ka. Average Holocene SSTs are 15.6°C for winter and 20.3°C for summer, whereas average glacial values were 14.2°C for winter and 19.5°C for summer. Compared to modern time, cooling of SSTs at the Last Glacial Maximum (LGM) was ~0.9°C in winter and ~1.5°C in summer. The shift from glacial to Holocene temperatures began at 14.25 14C ka, warming by ~2°C until 12.85 14C ka when temperatures dipped back to glacial values at 11.65 14C ka. The timing of this return to glacial-like SST correlates well with the Antarctic Cold Reversal (ACR) rather than the Younger Dryas and documents that the influence of the ACR extended into the subtropics of the Southern Hemisphere, at least in this region of the southwest Pacific. By 10.55 14C ka an SST maximum in summer SSTs of up to 3°C warmer than modern occurred (?24°C), after which SST dropped, remaining at present-day temperatures since 9.3 14C ka. This early Holocene climatic optimum has been widely noted in the Southern Ocean, and this record indicates that this phenomenon also extended into the subtropics to the north of New Zealand.

Analytical pedestrian accident reconstruction using computer simulation. Final report.

Mode of access: Internet.

Peoples of the Near East without a national future.

"Prepared by William L. Westermann."

Training program for accident investigation and coding in the National Crash Severity Study. Final report.

National Highway Traffic Safety Administration, Washington, D.C.

National Crash Severity Study - quality control. Task V: analysis to refine spinout aspects of CRASH. Final report.

National Highway Traffic Safety Administration, Washington, D.C.

Volume one (1) - staged collision and damage data report for accident reconstruction of twenty five (25) test vehicles (1980 model year). Final report.

National Highway Traffic Safety Administration, Accident Investigation Division, Washington, D.C.