Modeling resting-state functional networks when the cortex falls asleep: local and global changes.

The transition from wakefulness to sleep represents the most conspicuous change in behavior and the level of consciousness occurring in the healthy brain. It is accompanied by similarly conspicuous changes in neural dynamics, traditionally exemplified by the change from "desynchronized" electroencephalogram activity in wake to globally synchronized slow wave activity of early sleep. However, unit and local field recordings indicate that the transition is more gradual than it might appear: On one hand, local slow waves already appear during wake; on the other hand, slow sleep waves are only rarely global. Studies with functional magnetic resonance imaging also reveal changes in resting-state functional connectivity (FC) between wake and slow wave sleep. However, it remains unclear how resting-state networks may change during this transition period. Here, we employ large-scale modeling of the human cortico-cortical anatomical connectivity to evaluate changes in resting-state FC when the model "falls asleep" due to the progressive decrease in arousal-promoting neuromodulation. When cholinergic neuromodulation is parametrically decreased, local slow waves appear, while the overall organization of resting-state networks does not change. Furthermore, we show that these local slow waves are structured macroscopically in networks that resemble the resting-state networks. In contrast, when the neuromodulator decrease further to very low levels, slow waves become global and resting-state networks merge into a single undifferentiated, broadly synchronized network.

Hsp90 inhibition induces both protein-specific and global changes in the ubiquitinome.

Inhibition of the essential chaperone Hsp90 with drugs causes a global perturbation of protein folding and the depletion of direct substrates of Hsp90, also called clients. Ubiquitination and proteasomal degradation play a key role in cellular stress responses, but the impact of Hsp90 inhibition on the ubiquitinome has not been characterized on a global scale. We used stable isotope labeling and antibody-based peptide enrichment to quantify more than 1500 protein sites modified with a Gly-Gly motif, the remnant of ubiquitination, in human T-cells treated with an Hsp90 inhibitor. We observed rapid changes in GlyGly-modification sites, with strong increases for some Hsp90 clients but also decreases for a majority of cellular proteins. A comparison with changes in total protein levels and protein synthesis and decay rates from a previous study revealed a complex picture with different regulatory patterns observed for different protein families. Overall the data support the notion that for Hsp90 clients GlyGly-modification correlates with targeting by the ubiquitin-proteasome system and decay, while for other proteins levels of GlyGly-modification appear to be mainly influenced by their synthesis rates. Therefore a correct interpretation of changes in ubiquitination requires knowledge of multiple parameters. Data are available via ProteomeXchange with identifier PXD001549. BIOLOGICAL SIGNIFICANCE: Proteostasis, i.e. the capacity of the cell to maintain proper synthesis and maturation of proteins, is a fundamental biological process and its perturbations have far-reaching medical implications e.g. in cancer or neurodegenerative diseases. Hsp90 is an essential chaperone responsible for the correct maturation and stability of a number of key proteins. Inhibition of Hsp90 triggers a global stress response caused by accumulation of misfolded chains, which have to be either refolded or eliminated by protein degradation pathways such as the Ubiquitin-Proteasome System (UPS). We present the first global assessment of the changes in the ubiquitinome, the subset of ubiquitin-modified proteins, following Hsp90 inhibition in human T-cells. The results provide clues on how cells respond to a specific proteostasis challenge. Furthermore, our data also suggest that basal ubiquitination levels for most proteins are influenced by synthesis rates. This has broad significance as it implies that a proper interpretation of data on ubiquitination levels necessitates simultaneous knowledge of other parameters.

Global changes in gene expression observed at the transition from growth to stationary phase in Listeria monocytogenes ScottA batch culture

Listeria monocytogenes is a food-borne Gram-positive bacterium that is responsible for a variety of infections (worldwide) annually. The organism is able to survive a variety of environmental conditions and stresses, however, the mechanisms by which L. monocytogenes adapts to environmental change are yet to be fully elucidated. An understanding of the mechanism(s) by which L. monocytogenes survives unfavourable environmental conditions will aid in developing new food processing methods to control the organism in foodstuffs. We have utilized a proteomic approach to investigate the response of L. monocytogenes batch cultures to the transition from exponential to stationary growth phase. Proteomic analysis showed that batch cultures of L. monocytogenes perceived stress and began preparations for stationary phase much earlier (approximately A(600) = 0.75, mid-exponential) than predicted by growth characteristics alone. Global analysis of the proteome revealed that the expression levels of more than 50% of all proteins observed changed significantly over a 7-9 h period during this transition phase. We have highlighted ten proteins in particular whose expression levels appear to be important in the early onset of the stationary phase. The significance of these findings in terms of functionality and the mechanistic picture are discussed.

Direct soil moisture controls of future global soil carbon changes: An important source of uncertainty

The nature of the climate���carbon cycle feedback depends critically on the response of soil carbon to climate, including changes in moisture. However, soil moisture���carbon feedback responses have not been investigated thoroughly. Uncertainty in the response of soil carbon to soil moisture changes could arise from uncertainty in the relationship between soil moisture and heterotrophic respiration. We used twelve soil moisture���respiration functions (SMRFs) with a soil carbon model (RothC) and data from a coupled climate���carbon cycle general circulation model to investigate the impact of direct heterotrophic respiration dependence on soil moisture on the climate carbon cycle feedback. Global changes in soil moisture acted to oppose temperature���driven decreases in soil carbon and hence tended to increase soil carbon storage. We found considerable uncertainty in soil carbon changes due to the response of soil respiration to soil moisture. The use of different SMRFs resulted in both large losses and small gains in future global soil carbon stocks, whether considering all climate forcings or only moisture changes. Regionally, the greatest range in soil carbon changes across SMRFs was found where the largest soil carbon changes occurred. Further research is needed to constrain the soil moisture���respiration relationship and thus reduce uncertainty in climate���carbon cycle feedbacks. There may also be considerable uncertainty in the regional responses of soil carbon to soil moisture changes since climate model predictions of regional soil moisture changes are less coherent than temperature changes.

Reshaping the global agricultural landscape: perspectives from Brazil

This article highlights the main changes observed in Brazilian agriculture and analyzes the connections of the observed changes in global agriculture. My approach to the analysis focuses the main drivers of changes, where institutions play a central role. Three driving forces are are considered: first, the effects of global demand for food, fiber, and energy; second, the sustainability debate; and third, the bio-energy paradigm. Each driver presents both local as well as global effects. The article does not emphasize the impact changes in Brazil had on the global agricultural landscape but argues that the impacts run from local and global changes, which cannot be discussed separately.

An evaluation of the changes in malocclusion index scores over a 25-year period

Background: The measured values of specific traits of occlusion may be subject to significant change due to growth and maturation of the dentofacial structures. Some traits may show improvement while others may show deterioration. Rarely is there an opportunity to examine a sample of occlusions 25 years after the acquisition of the original set of records. This study examines the changes in traits of occlusion in a sample of 46 subjects who were originally examined between 1971-1973 and for whom records were again obtained in 1998. Methods: The 46 patients were a sub-group of a previously selected randomised school-based sample and study models obtained in 1971-1973 were still available. New models for each patient were obtained in 1998. Of the 46 subjects, only eight had received orthodontic treatment. Results: Assessments of the changes in specific traits were made using the methods proposed in the Harry L Draker, California Modification (HLD Cal Mod) index. This simple index was chosen because the main component traits were well defined and, when analysed separately, reflected changes with time. The total index score gave a broad indication of the global changes in the individual's occlusion. The five basic traits of the HLD index include overjet, overbite, openbite, mandibular protrusion and labio-lingual spread. Three additional traits (ectopic eruption, anterior crowding and posterior crossbite) are used in the HLD Cal Mod index. These traits provided a useful reflection of occlusal changes with time. Measurements were made with reference to specifications and the details outlined in the HLD Cal Mod protocol. The results revealed an increase in total index scores over time with a significant increase in lower labio-lingual spread associated with an increased score in anterior crowding. Overjet and overbite, however, displayed a significant decrease with time. Conclusions: These findings are in keeping with previous studies and highlight the importance of time as a significant issue in the assessment of occlusion.

Brazil's global aspirations and their implications for the relationship with Argentina in the framework of MERCOSUR

Disserta����o de mestrado em Rela����es Internacionais

Late Pliensbachian-Early Toarcian (Early Jurassic) environmental changes in an epicontinental basin of NW Europe (Causses area, central France): A micropaleontological and geochemical approach

We present an integrated work based on calcareous nannofossil and benthic foraminiferal assemblages, and geochemical analyses of two Upper Pliensbachian-Lower Toarcian sections located in the central-South France. The studied sections, Tournadous and Saint-Paul-des-Fonts, represent the proximal and the distal part, respectively, of the Jurassic Causses Basin, one of the small, partly enclosed basins belonging to the epicontinental shelf of the NW Tethys. At the transition from Late Pliensbachian to Early Toarcian, the Causses Basin recorded an emersion in response to the global sea-level fall. Our data indicate severe environmental conditions of marine waters, including salinity decrease and anoxia development, occurring in the Early Toarcian. The acme of this deterioration coincides with the Early Toarcian Anoxic Event (T-OAE) but, due to the restricted nature of the basin. anoxia persisted until the end of the Early Toarcian. mainly in the deeper parts of the basin. The micronutrients and organic organic-matter fluxes were probably high during the entire studied time interval, as shown by nannofossil and foraminiferal assemblages. However, nannoplankton production drastically decreased during the T-OAE, as demonstrated by very low nannofossil fluxes, and only taxa tolerant to low-saline surface waters could thrive. At the same time, benthic foraminifers temporarily disappeared in response to sea-bottom anoxia. Our study demonstrates that environmental changes related to the T-OAE are well-recorded even in small, partly enclosed basins of NW Europe, like the Causses Basin. Within this area, the effects of global changes. like sea sea-level and temperature fluctuations, are modulated by local conditions mainly controlled by the morphology of the basin. (C) 2008 Elsevier B.V. All rights reserved.

Niche, distribution and global change : modeling insights into biogeography and conservation biology Olivier Broennimann

RESUME Les ��vidences montrant que les changements globaux affectent la biodiversit�� s'accumulent. Les facteurs les plus influant dans ce processus sont les changements et destructions d'habitat, l'expansion des esp��ces envahissantes et l'impact des changements climatiques. Une ��valuation pertinente de la r��ponse des esp��ces face �� ces changements est essentielle pour proposer des mesures permettant de r��duire le d��clin actuel de la biodiversit��. La mod��lisation de la r��partition d'esp��ces bas��e sur la niche (NBM) est l'un des rares outils permettant cette ��valuation. N��anmoins, leur application dans le contexte des changements globaux repose sur des hypoth��ses restrictives et demande une interpr��tation critique. Ce travail pr��sente une s��rie d'��tudes de cas investiguant les possibilit��s et limitations de cette approche pour pr��dire l'impact des changements globaux. Deux ��tudes traitant des menaces sur les esp��ces rares et en danger d'extinction sont pr��sent��es. Les caract��ristiques ��co-g��ographiques de 118 plantes avec un haut degr�� de priorit�� de conservation sont revues. La pr��valence des types de raret�� sont analys��es en relation avec leur risque d'extinction UICN. La revue souligne l'importance de la conservation �� l'��chelle r��gionale. Une ��valuation de la raret�� �� ��chelle globale peut ��tre trompeuse pour certaine esp��ces car elle ne tient pas en compte des diff��rents degr��s de raret�� que pr��sente une esp��ce �� diff��rentes ��chelles spatiales. La deuxi��me ��tude test une approche pour am��liorer l'��chantillonnage d'esp��ces rares en incluant des phases it��ratives de mod��lisation et d'��chantillonnage sur le terrain. L'application de l'approche en biologie de la conservation (illustr��e ici par le cas du chardon bleu, Eryngium alpinum), permettrait de r��duire le temps et les co��ts d'��chantillonnage. Deux ��tudes sur l'impact des changements climatiques sur la faune et la flore africaine sont pr��sent��es. La premi��re ��tude ��value la sensibilit�� de 227 mammif��res africains face aux climatiques d'ici 2050. Elle montre qu'un nombre important d'esp��ces pourrait ��tre bient��t en danger d'extinction et que les parcs nationaux africains (principalement ceux situ�� en milieux x��riques) pourraient ne pas remplir leur mandat de protection de la biodiversit�� dans le futur. La seconde ��tude mod��lise l'aire de r��partition en 2050 de 975 esp��ces de plantes end��miques du sud de l'Afrique. L'��tude propose l'inclusion de m��thodes am��liorant la pr��diction des risques li��s aux changements climatiques. Elle propose ��galement une m��thode pour estimer a priori la sensibilit�� d'une esp��ce aux changements climatiques �� partir de ses propri��t��s ��cologiques et des caract��ristiques de son aire de r��partition. Trois ��tudes illustrent l'utilisation des mod��les dans l'��tude des invasions biologiques. Une premi��re ��tude relate l'expansion de la laitue s��uvage (Lactuca serriola) vers le nord de l'Europe en lien avec les changements du climat depuis 250 ans. La deuxi��me ��tude analyse le potentiel d'invasion de la centaur��e tachet��e (Centaures maculosa), une mauvaise herbe import��e en Am��rique du nord vers 1890. L'��tude apporte la preuve qu'une esp��ce envahissante peut occuper une niche climatique diff��rente apr��s introduction sur un autre continent. Les mod��les bas��s sur l'aire native pr��disent de mani��re incorrecte l'entier de l'aire envahie mais permettent de pr��voir les aires d'introductions potentielles. Une m��thode alternative, incluant la calibration du mod��le �� partir des deux aires o�� l'esp��ce est pr��sente, est propos��e pour am��liorer les pr��dictions de l'invasion en Am��rique du nord. Je pr��sente finalement une revue de la litt��rature sur la dynamique de la niche ��cologique dans le temps et l'espace. Elle synth��tise les r��cents d��veloppements th��oriques concernant le conservatisme de la niche et propose des solutions pour am��liorer la pertinence des pr��dictions d'impact des changements climatiques et des invasions biologiques. SUMMARY Evidences are accumulating that biodiversity is facing the effects of global change. The most influential drivers of change in ecosystems are land-use change, alien species invasions and climate change impacts. Accurate projections of species' responses to these changes are needed to propose mitigation measures to slow down the on-going erosion of biodiversity. Niche-based models (NBM) currently represent one of the only tools for such projections. However, their application in the context of global changes relies on restrictive assumptions, calling for cautious interpretations. In this thesis I aim to assess the effectiveness and shortcomings of niche-based models for the study of global change impacts on biodiversity through the investigation of specific, unsolved limitations and suggestion of new approaches. Two studies investigating threats to rare and endangered plants are presented. I review the ecogeographic characteristic of 118 endangered plants with high conservation priority in Switzerland. The prevalence of rarity types among plant species is analyzed in relation to IUCN extinction risks. The review underlines the importance of regional vs. global conservation and shows that a global assessment of rarity might be misleading for some species because it can fail to account for different degrees of rarity at a variety of spatial scales. The second study tests a modeling framework including iterative steps of modeling and field surveys to improve the sampling of rare species. The approach is illustrated with a rare alpine plant, Eryngium alpinum and shows promise for complementing conservation practices and reducing sampling costs. Two studies illustrate the impacts of climate change on African taxa. The first one assesses the sensitivity of 277 mammals at African scale to climate change by 2050 in terms of species richness and turnover. It shows that a substantial number of species could be critically endangered in the future. National parks situated in xeric ecosystems are not expected to meet their mandate of protecting current species diversity in the future. The second study model the distribution in 2050 of 975 endemic plant species in southern Africa. The study proposes the inclusion of new methodological insights improving the accuracy and ecological realism of predictions of global changes studies. It also investigates the possibility to estimate a priori the sensitivity of a species to climate change from the geographical distribution and ecological proprieties of the species. Three studies illustrate the application of NBM in the study of biological invasions. The first one investigates the Northwards expansion of Lactuca serriola L. in Europe during the last 250 years in relation with climate changes. In the last two decades, the species could not track climate change due to non climatic influences. A second study analyses the potential invasion extent of spotted knapweed, a European weed first introduced into North America in the 1890s. The study provides one of the first empirical evidence that an invasive species can occupy climatically distinct niche spaces following its introduction into a new area. Models fail to predict the current full extent of the invasion, but correctly predict areas of introduction. An alternative approach, involving the calibration of models with pooled data from both ranges, is proposed to improve predictions of the extent of invasion on models based solely on the native range. I finally present a review on the dynamic nature of ecological niches in space and time. It synthesizes the recent theoretical developments to the niche conservatism issues and proposes solutions to improve confidence in NBM predictions of the impacts of climate change and species invasions on species distributions.

Do geographic distribution, niche property and life form explain plants' vulnerability to global change?

We modelled the future distribution in 2050 of 975 endemic plant species in southern Africa distributed among seven life forms, including new methodological insights improving the accuracy and ecological realism of predictions of global changes studies by: (i) using only endemic species as a way to capture the full realized niche of species, (ii) considering the direct impact of human pressure on landscape and biodiversity jointly with climate, and (iii) taking species' migration into account. Our analysis shows important promises for predicting the impacts of climate change in conjunction with land transformation. We have shown that the endemic flora of Southern Africa on average decreases with 41% in species richness among habitats and with 39% on species distribution range for the most optimistic scenario. We also compared the patterns of species' sensitivity with global change across life forms, using ecological and geographic characteristics of species. We demonstrate here that species and life form vulnerability to global changes can be partly explained according to species' (i) geographical distribution along climatic and biogeographic gradients, like climate anomalies, (ii) niche breadth or (iii) proximity to barrier preventing migration. Our results confirm that the sensitivity of a given species to global environmental changes depends upon its geographical distribution and ecological proprieties, and makes it possible to estimate a priori its potential sensitivity to these changes.

Salinity changes in the world ocean since 1950 in relation to changing surface freshwater fluxes

Global hydrographic and air���sea freshwater flux datasets are used to investigate ocean salinity changes over 1950���2010 in relation to surface freshwater flux. On multi-decadal timescales, surface salinity increases (decreases) in evaporation (precipitation) dominated regions, the Atlantic���Pacific salinity contrast increases, and the upper thermocline salinity maximum increases while the salinity minimum of intermediate waters decreases. Potential trends in E���P are examined for 1950���2010 (using two reanalyses) and 1979���2010 (using four reanalyses and two blended products). Large differences in the 1950���2010 E���P trend patterns are evident in several regions, particularly the North Atlantic. For 1979���2010 some coherency in the spatial change patterns is evident but there is still a large spread in trend magnitude and sign between the six E���P products. However, a robust pattern of increased E���P in the southern hemisphere subtropical gyres is seen in all products. There is also some evidence in the tropical Pacific for a link between the spatial change patterns of salinity and E���P associated with ENSO. The water cycle amplification rate over specific regions is subsequently inferred from the observed 3-D salinity change field using a salt conservation equation in variable isopycnal volumes, implicitly accounting for the migration of isopycnal surfaces. Inferred global changes of E���P over 1950���2010 amount to an increase of 1 �� 0.6 % in net evaporation across the subtropics and an increase of 4.2 �� 2 % in net precipitation across subpolar latitudes. Amplification rates are approximately doubled over 1979���2010, consistent with accelerated broad-scale warming but also coincident with much improved salinity sampling over the latter period.