Population Variation and Genetic Control of Modular Chromatin Architecture in Humans.

Chromatin state variation at gene regulatory elements is abundant across individuals, yet we understand little about the genetic basis of this variability. Here, we profiled several histone modifications, the transcription factor (TF) PU.1, RNA polymerase II, and gene expression in lymphoblastoid cell lines from 47 whole-genome sequenced individuals. We observed that distinct cis-regulatory elements exhibit coordinated chromatin variation across individuals in the form of variable chromatin modules (VCMs) at sub-Mb scale. VCMs were associated with thousands of genes and preferentially cluster within chromosomal contact domains. We mapped strong proximal and weak, yet more ubiquitous, distal-acting chromatin quantitative trait loci (cQTL) that frequently explain this variation. cQTLs were associated with molecular activity at clusters of cis-regulatory elements and mapped preferentially within TF-bound regions. We propose that local, sequence-independent chromatin variation emerges as a result of genetic perturbations in cooperative interactions between cis-regulatory elements that are located within the same genomic domain.

Addition of MR imaging features and genetic biomarkers strengthens glioblastoma survival prediction in TCGA patients.

PURPOSE: The purpose of our study was to assess whether a model combining clinical factors, MR imaging features, and genomics would better predict overall survival of patients with glioblastoma (GBM) than either individual data type. METHODS: The study was conducted leveraging The Cancer Genome Atlas (TCGA) effort supported by the National Institutes of Health. Six neuroradiologists reviewed MRI images from The Cancer Imaging Archive (http://cancerimagingarchive.net) of 102 GBM patients using the VASARI scoring system. The patients' clinical and genetic data were obtained from the TCGA website (http://www.cancergenome.nih.gov/). Patient outcome was measured in terms of overall survival time. The association between different categories of biomarkers and survival was evaluated using Cox analysis. RESULTS: The features that were significantly associated with survival were: (1) clinical factors: chemotherapy; (2) imaging: proportion of tumor contrast enhancement on MRI; and (3) genomics: HRAS copy number variation. The combination of these three biomarkers resulted in an incremental increase in the strength of prediction of survival, with the model that included clinical, imaging, and genetic variables having the highest predictive accuracy (area under the curve 0.679±0.068, Akaike's information criterion 566.7, P<0.001). CONCLUSION: A combination of clinical factors, imaging features, and HRAS copy number variation best predicts survival of patients with GBM.

Genetic variation in the European hake, Merluccius merluccius. Description of protein loci and genetic divergence between Atlantic and Mediterranean populations = Anàlisi de la variabilitat genètica en el lluç europeu, Merluccius merluccius. Descripció dels loci electroforètics i divergència genètica entre les poblacions atlàntica i mediterrània

We examined the genetic population structure of the european hake (Merluccius merluccius) using electrophoretically detectable population markers in 35 protein loci. Samples were collected from 7 locations in the Atlantic Ocean and Mediterranean Sea. Six loci were polymorphic using the 0.05 criterion of polymorphism. Sample heterozigosities ranged from 0.052 to 0.072 and averaged 0.0625. In this study, significant allele frequency differences were detected between Atlantic and Mediterranean populations in three polymorphic loci: GAPDH-1*, GPI-2* and SOD-1*. Two major genetic groups were considered: a North-Atlantic stock and the Mediterranean stock. The Nei genetic distance, D, (based on 33 loci) between samples from these two groups ranged from 0.002 to 0.006. Genetic differenciation between these areas appears to reflect the barrier effect of Strait of Gibraltar. On average over loci, 96.92 % of the total gene diversity was contained within samples, 0.23 % expressed differences among locations within areas, and 2.64 % differences between regions. A review of morphological variation together with the genetic data presented here suggest that the populations of hake from these areas are subdivided into two different stocks: the North-Atlantic stock and the Mediterranean stock. The most conservative approach to the management of these stocks is to consider the Atlantic and Mediterranean stocks independently from oneanother

Sociodemographic, behavioral and genetic determinants of allostatic load in a Swiss population-based study.

Allostatic load (AL) is a marker of physiological dysregulation which reflects exposure to chronic stress. High AL has been related to poorer health outcomes including mortality. We examine here the association of socioeconomic and lifestyle factors with AL. Additionally, we investigate the extent to which AL is genetically determined. We included 803 participants (52% women, mean age 48±16years) from a population and family-based Swiss study. We computed an AL index aggregating 14 markers from cardiovascular, metabolic, lipidic, oxidative, hypothalamus-pituitary-adrenal and inflammatory homeostatic axes. Education and occupational position were used as indicators of socioeconomic status. Marital status, stress, alcohol intake, smoking, dietary patterns and physical activity were considered as lifestyle factors. Heritability of AL was estimated by maximum likelihood. Women with a low occupational position had higher AL (low vs. high OR=3.99, 95%CI [1.22;13.05]), while the opposite was observed for men (middle vs. high OR=0.48, 95%CI [0.23;0.99]). Education tended to be inversely associated with AL in both sexes(low vs. high OR=3.54, 95%CI [1.69;7.4]/OR=1.59, 95%CI [0.88;2.90] in women/men). Heavy drinking men as well as women abstaining from alcohol had higher AL than moderate drinkers. Physical activity was protective against AL while high salt intake was related to increased AL risk. The heritability of AL was estimated to be 29.5% ±7.9%. Our results suggest that generalized physiological dysregulation, as measured by AL, is determined by both environmental and genetic factors. The genetic contribution to AL remains modest when compared to the environmental component, which explains approximately 70% of the phenotypic variance.

Ecological change predicts population dynamics and genetic diversity over 120 000 years.

While ecological effects on short-term population dynamics are well understood, their effects over millennia are difficult to demonstrate and convincing evidence is scant. Using coalescent methods, we analysed past population dynamics of three lizard species (Psammodromus hispanicus, P. edwardsianus, P. occidentalis) and linked the results with climate change data covering the same temporal horizon (120 000 years). An increase in population size over time was observed in two species, and in P. occidentalis, no change was observed. Temporal changes in temperature seasonality and the maximum temperature of the warmest month were congruent with changes in population dynamics observed for the three species and both variables affected population density, either directly or indirectly (via a life-history trait). These results constitute the first solid link between ecological change and long-term population dynamics. The results moreover suggest that ecological change leaves genetic signatures that can be retrospectively traced, providing evidence that ecological change is a crucial driver of genetic diversity and speciation.

Virus Infections in Early Childhood, Cow’s Milk Formula Exposure and Genetic Predisposition in the Development of Diabetes-Associated Autoimmunity

Varhaislapsuuden virusinfektioiden, lehmänmaitopohjaisen äidinmaitovastikeen ja geneettisen alttiuden merkitys diabetekseen liittyvän autoimmuniteetin kehittymisessä Tyypin 1 diabetes on autoimmuunisairaus, joka syntyy haiman insuliinia tuottavien beta-solujen tuhouduttua elimistön oman immuunipuolustusjärjestelmän hyökkäyksen seurauksena. Sekä perimän että ympäristötekijöiden arvellaan vaikuttavan tautiprosessiin, mutta taudin tarkkaa syntymekanismia ei tunneta. Tutkimuksen tarkoituksena oli selvittää varhaislapsuuden ympäristötekijöiden vaikutusta beta-soluautoimmuniteetin syntyyn, erityispaino tutkimuksessa oli ympäristötekijöiden yhteisvaikutuksessa sekä geneettisten riskitekijöiden ja ympäristötekijöiden vuorovaikutuksessa. Varhaislapsuudessa sairastettu sytomegalovirus- tai enterovirusinfektio ei lisännyt beta-soluautoimmuniteetin riskiä lapsilla, joilla on geneettisesti kohonnut riski sairastua tyypin 1 diabetekseen. Ennen puolen vuoden ikää sairastettu rotavirusinfektio lisäsi hieman tyypin 1 diabetekseen liittyvän autoimmuniteetin riskiä. Tarkemmassa analyysissa varhaislapsuuden enterovirusinfektio osoittautui kuitenkin autovasta-aineiden muodostumisen riskitekijäksi niiden lasten joukossa, jotka olivat saaneet lehmänmaitopohjaista äidinmaidon vastiketta ensimmäisten elinkuukausien aikana. Tämä löydös viittaa enterovirusinfektion ja lehmänmaitopohjaisen vastikkeen yhteisvaikutukseen tyypin 1 diabetekseen liittyvän autoimmuniteetin synnyssä. Löydösten mukaan PTPN22 geenin C1858T polymorfismi vaikuttaa CD4+ T solujen aktivaatioon ja proliferaatiovasteeseen, 1858T alleeliin liittyy alentunut T-soluresepto-rivälitteinen aktivaatio. 1858T alleelin kantajuuteen liittyy lisäksi lisääntynyt autovasta-aineiden ja kliinisen diabeteksen ilmaantuvuus. Tämä yhteys rajoittui yksilöihin, jotka olivat altistuneet lehmänmaitopohjaiselle vastikkeelle ennen kuuden kuukauden ikää. Tulosten mukaan sekä ympäristötekijöiden väliset yhteisvaikutukset että perimä vaikuttavat yksittäisen ympäristötekijän merkitykseen tyypin 1 diabetekseen liittyvän autoimmuniteetin synnyssä. Nämä yhteisvaikutukset ympäristötekijöiden kesken ja perimän ja ympäristötekijöiden välillä selittävät aiemmin julkaistujen tulosten ristiriittaisuutta tutkimuksissa, joissa on analysoitu vain yhden ympäristötekijän vaikutusta diabeteksen ilmaantuvuuteen.

A Química na agricultura: perspectivas para o desenvolvimento de tecnologias sustentáveis

Food production and preservation of the environment are among the challenges faced by contemporary society. In Brazil, as in most parts of the world, the possibility of increasing the agricultural area is limited by several factors. Thus, an increase in productivity through the application of innovative technologies is regarded as the best solution to overcome such a problem. For long, chemistry has contributed to agricultural innovations such as synthetic pesticides for pest management. However, due to the well-known adverse effects of these compounds, new "greener" strategies are being explored. Research in chemical ecology, in combination with other emerging sciences, is leading to the development of new technologies such as plant-based pesticides (biopesticides); synthetic pheromones and plant volatile organic compounds, both of them to manipulate insect behavior; chemical elicitors to boost plant resistance; and genetic engineering of plant varieties. In these, chemistry plays an important role in the identification and synthesis of functional compounds. These techniques may be incorporated in integrated pest management programs and may contribute to a sustainable agriculture in the future.

Noctuidae-induced plant volatiles: current situation and prospects

Noctuids are phytophagous lepidopterans with some species causing significant damage to agriculture. The host plants, in turn, have developed defense mechanisms to cope with them, for instance chemical defenses. In this study we review the literature on plant volatiles induced by noctuids, and discuss the methodologies used to induce the production of volatiles that are usually employed in plant defense mechanisms. Future prospects involving this line of research in pest control are also discussed.

Vocalization of broilers can be used to identify their sex and genetic strain

In order to reach higher broiler performance, farmers target losses reduction. One way to make this possible is by rearing sexed broilers as male and female present diverse performance due to their physiological differences. Birds from different genetic strain also have a distinct performance at the same age. Considering that sexed flocks may present higher performance this study aimed to identify one-day-old chicks’ sex throughout their vocalization. This research also investigated the possibility of identifying the genetic strain by their vocalization attributes. A total of 120 chicks, half of them were from Cobb® genetic strain and the other half from Ross® genetic strain. From each group, a total of 30 were males and 30 females, which were previously separated by sex using their secondary physiological characteristics at the hatchery. Vocalizations audio recording was done inside a semi-anechoic chamber using a unidirectional microphone connected to an audio input of a digital recorder. Vocalizations were recorded for two minutes. Acoustic characteristics of the sounds were analyzed being calculated the fundamental frequency Pitch, the sound intensity, the first formant, and second formant. Results indicated that the vocalizations of both sexes could be identified by the second formant, and the genetic strain was detected by both the second formant and the Pitch.

Pluripotency and genetic stability of human pluripotent stem cells

Pluripotent cells have the potential to differentiate into all somatic cell types. As the adult human body is unable to regenerate various tissues, pluripotent cells provide an attractive source for regenerative medicine. Human embryonic stem cells (hESCs) can be isolated from blastocyst stage embryos and cultured in the laboratory environment. However, their use in regenerative medicine is restricted due to problems with immunosuppression by the host and ethical legislation. Recently, a new source of pluripotent cells was established via the direct reprogramming of somatic cells. These human induced pluripotent stem cells (hiPSCs) enable the production of patient specific cell types. However, numerous challenges, such as efficient reprogramming, optimal culture, directed differentiation, genetic stability and tumor risk need to be solved before the launch of therapeutic applications. The main objective of this thesis was to understand the unique properties of human pluripotent stem cells. The specific aims were to identify novel factors involved in maintaining pluripotency, characterize the effects of low oxygen culture on hESCs, and determine the high resolution changes in hESCs and hiPSCs during culture and reprogramming. As a result, the previously uncharacterized protein L1TD1 was determined to be specific for pluripotent cells and essential for the maintenance of pluripotency. The low oxygen culture supported undifferentiated growth and affected expression of stem cell associated transcripts. High resolution screening of hESCs identified a number of culture induced copy number variations and loss of heterozygosity changes. Further, screening of hiPSCs revealed that reprogramming induces high resolution alterations. The results obtained in this thesis have important implications for stem cell and cancer biology and the therapeutic potential of pluripotent cells.

Improvement of wet and dry web properties in papermaking by controlling water and fiber quality

Pappersindustrin står inför många utmaningar och bör uppfylla krav som ställs av t.ex. marknadstrender och slutanvändare. Snabbare och effektivare processer ställer även större krav på pappersbanans mekaniska egenskaper. Avbrott i produktionen sker inte enbart pga. låg styrka utan orsaken kan även vara en för låg spänning i pappersbanan. De flesta problemen sker vid våtpressen och/eller i början av torkpartiet då papprets torrhalt är 30-70 %. Spänningen hålls inte konstant efter töjning, utan sjunker pga. papprets relaxering, som till största delen sker då pappret flyttas från pressen till torkpartiet. Ur forskningssynvinkel öppnar en smidigt fungerande verksamhet med potentiella energibesparingar upp möjligheterna för förbättring av befintliga processer. I detta arbete undersöktes hur olika faktorer inverkar på fibernätverkets avvattning, initiala våtstyrka och relaxering samt också på slutproduktens mekaniska egenskaper och ytegenskaper. I första delen ändrades processvattnets egenskaper, såsom pH, konduktivitet och ytspänning. Ytspänningen varierades genom tillsatts av ett nonjoniskt ytaktivt ämne, s.k. surfaktant. Fiberegenskaperna modifierades också. Fibern maldes antingen genom en mild eller genom en hård process. Effekten av finmaterial undersöktes genom att tillsätta finmaterial till den ursprungliga massan eller genom att avlägsna finmaterialet från den malda massan. I den sista delen användes en hemicellulosa, som finns i stora mängder i gran, som tillsatsmedel. Förutom naturliga galaktoglukomannaner (GGM), tillverkades också en katjoniserad, en karboximetylerad samt en iminerad, amfifil GGM. Dessa användes i pappersmassa eller sprayades på ytan av ett nybildat ark. Resultaten, som erhölls i denna avhandling, bildar en värdefull kunskapsbas, som kan användas för kontroll och reglering av pappersmaskinens körbarhet och papperskvalitet.

Effect of plant regulators on growth and flowering of 'Meyer' zoysiagrass

This trial aimed to evaluate the effect of sequential applications of different plant regulators over growth and flower rachis emission of 'Meyer' zoysiagrass (Zoysia japonica). The study was conducted on 15-month old green turfgrass under a randomized complete block design with four replications. The following plant regulator and doses were tested: trinexapac-ethyl (113+113, 226+113, 226+226, 452+113, 452+226, 452+452, 678+339 e 904+452 g a.i./ha-1), prohexadione-calcium (100+100 e 200+200 g a.i. ha-1) and bispyribac-sodium (40+40 e 60+60 g a.i. ha-1), as well as an untreated control. The turfgrass was mowed again at 3.0 cm aboveground and the second plant regulator was applied when 'Meyer' zoysiagrass was between 5.0 and 6.0 cm high. The effect of the treatments was visually rated for visual injury, plant height, height and number of flower rachis, and total dry mass production of clippings. Only bispyribac-sodium had visual symptoms of injury on 'Meyer' zoysiagrass, and no intoxication was observed at 28 days after the second application (DAAB). The sequential applications of trinexapac-ethyl, prohexadione-calcium and bispyribac-sodium reduced by more than 80% the total clipping dry mass produced by 'Meyer' zoysiagrass. All the plant regulators tested also showed promising results in reducing the height and emission of rachis, especially when trinexapac-ethyl was applied at the doses 452+452, 678+339 and 904+452 g a.i. ha-1. 'Meyer' zoysiagrass turfgrass can be handled with the sequential application of a plant regulator, which reduces the need for mowing over a period up to 110 days after the application of the second plant regulator, and it also avoids deleterious visual effects over turfgrass.