Effects of neural nitric oxide synthase gene inactivation on the neurodocrine stress response in mice

Neural nitric oxide synthase, neuroendocrine stress response, forced swimming, nNOS KO mice, hypothalamus, adrenal gland

APOE and LDLR Gene Polymorphisms and Dyslipidemia Tracking. Rio de Janeiro Study

Background:Studies show an association between changes in apolipoprotein E (ApoE) and LDLR receptor with the occurrence of dyslipidemia.Objectives:To investigate the association between polymorphisms of the APOE (ε2, ε3, ε4) and LDLR (A370T) genes with the persistence of abnormal serum lipid levels in young individuals followed up for 17 years in the Rio de Janeiro Study.Methods:The study included 56 individuals (35 males) who underwent three assessments at different ages: A1 (mean age 13.30 ± 1.53 years), A2 (22.09 ± 1.91 years) and A3 (31.23 ± 1.99 years). Clinical evaluation with measurement of blood pressure (BP) and body mass index (BMI) was conducted at all three assessments. Measurement of waist circumference (WC) and serum lipids, and analysis of genetic polymorphisms by PCR-RFLP were performed at A2 and A3. Based on dyslipidemia tracking, three groups were established: 0 (no abnormal lipid value at A2 and A3), 1 (up to one abnormal lipid value at A2 or A3) and 2 (one or more abnormal lipid values at A2 and A3).Results:Compared with groups 0 and 1, group 2 presented higher mean values of BP, BMI, WC, LDL-c and TG (p < 0.01) and lower mean values of HDL-c (p = 0.001). Across the assessments, all individuals with APOE genotypes ε2/ε4 and ε4/ε4 maintained at least one abnormal lipid variable, whereas those with genotype ε2/ε3 did not show abnormal values (χ2 = 16.848, p = 0.032). For the LDLR genotypes, there was no significant difference among the groups.Conclusions:APOE gene polymorphisms were associated with dyslipidemia in young individuals followed up longitudinally from childhood.

Estudos experimentais sôbre a origem do milho

1) It may seem rather strange that, in spite of the efforts of a considerable number of scientists, the problem of the origin of indian corn or maize still has remained an open question. There are no fossil remains or archaeological relics except those which are quite identical with types still existing. (Fig. 1). The main difficulty in finding the wild ancestor- which may still exist - results from the fact that it has been somewhat difficult to decide what it should be like and also where to look for it. 2) There is no need to discuss the literature since an excellent review has recently been published by MANGELSDORF and REEVES (1939). It may be sufficient to state that there are basically two hypotheses, that of ST. HILAIRE (1829) who considered Brazilian pod corn as the nearest relative of wild corn still existing, and that of ASCHERSON (1875) who considered Euchlaena from Central America as the wild ancestor of corn. Later hypotheses represent or variants of these two hypotheses or of other concepts, howewer generally with neither disproving their predecessors nor showing why the new hypotheses were better than the older ones. Since nearly all possible combinations of ideas have thus been put forward, it har- dly seems possible to find something theoretically new, while it is essential first to produce new facts. 3) The studies about the origin of maize received a new impulse from MANGELSDORF and REEVES'S experimental work on both Zea-Tripsacum and Zea-Euchlaena hybrids. Independently I started experiments in 1937 with the hope that new results might be obtained when using South American material. Having lost priority in some respects I decided to withold publication untill now, when I can put forward more concise ideas about the origin of maize, based on a new experimental reconstruction of the "wild type". 4) The two main aspects of MANGELSDORF and REEVES hypothesis are discussed. We agree with the authors that ST. HILAIRE's theory is probably correct in so far as the tunicata gene is a wild type relic gene, but cannot accept the reconstruction of wild corn as a homozygous pod corn with a hermaphroditic tassel. As shown experimentally (Fig. 2-3) these tassels have their central spike transformed into a terminal, many rowed ear with a flexible rachis, while possessing at the same time the lateral ear. Thus no explanation is given of the origin of the corn ear, which is the main feature of cultivated corn (BRIEGER, 1943). The second part of the hypothesis referring to the origin of Euchlaena from corn, inverting thus ASCHERSON's theory, cannot be accepted for several reasons, stated in some detail. The data at hand justify only the conclusion that both genera, Euchlaena and Zea, are related, and there is as little proof for considering the former as ancestor of the latter as there is for the new inverse theory. 5) The analysis of indigenous corn, which will be published in detail by BRIEGER and CUTLER, showed several very primitive characters, but no type was found which was in all characters sufficiently primitive. A genetical analysis of Paulista Pod Corn showed that it contains the same gene as other tunicates, in the IV chromosome, the segregation being complicated by a new gametophyte factor Ga3. The full results of this analysis shall be published elsewhere. (BRIEGER). Selection experiments with Paulista Pod Corn showed that no approximation to a wild ancestor may be obtained when limiting the studies to pure corn. Thus it seemed necessary to substitute "domesticated" by "wild type" modifiers, and the only means for achieving this substitution are hybridizations with Euchlaena. These hybrids have now been analysed init fourth generation, including backcrosses, and, again, the full data will be published elsewhere, by BRIEGER and ADDISON. In one present publication three forms obtained will be described only, which represent an approximation to wild type corn. 6) Before entering howewer into detail, some arguments against ST. HILAIRE's theory must be mentioned. The premendelian argument, referring to the instability of this character, is explained by the fact that all fertile pod corn plants are heterozygous for the dominant Tu factor. But the sterility of the homozygous TuTu, which phenotypically cannot be identified, is still unexplained. The most important argument against the acceptance of the Tunicata faetor as wild type relic gene was removed recently by CUTLER (not yet published) who showed that this type has been preserved for centuries by the Bolivian indians as a mystical "medicine". 7) The main botanical requirements for transforming the corn ear into a wild type structure are stated, and alternative solutions given. One series of these characters are found in Tripsacum and Euchlaena : 2 rows on opposite sides of the rachis, protection of the grains by scales, fragility of the rachis. There remains the other alternative : 4 rows, possibly forming double rows of female and male spikelets, protection of kernels by their glumes, separation of grains at their base from the cob which is thin and flexible. 8) Three successive stages in the reconstruction of wild corn, obtained experimentally, are discussed and illustrated, all characterized by the presence of the Tu gene. a) The structure of the Fl hybrids has already been described in 1943. The main features of the Tunicata hybrids (Fig. -8), when compared with non-tunicate hybrids (Fig. 5-6), consist in the absence of scaly protections, the fragility of the rachis and finally the differentiation of the double rows into one male and one female spikelet. As has been pointed out, these characters represent new phenotypic effects of the tunicate factor which do not appear in the presence of pure maize modifiers. b) The next step was observed among the first backcross to teosinte (Fig. 9). As shown in the photography, Fig. 9D, the features are essencially those of the Fl plants, except that the rachis is more teosinte like, with longer internodes, irregular four-row-arrangement and a complete fragility on the nodes. c) In the next generation a completely new type appeared (Fig. 10) which resembles neither corn nor teosinte, mainly in consequence of one character: the rachis is thin and flexible and not fragile, while the grains have an abscission layer at the base, The medium sized, pointed, brownish and hard granis are protected by their well developed corneous glumes. This last form may not yet be the nearest approach to a wild grass, and I shall try in further experiments to introduce other changes such as an increase of fertile flowers per spikelet, the reduction of difference between terminal and lateral inflorescences, etc.. But the nature of the atavistic reversion is alveadwy such that it alters considerably our expectation when looking for a still existing wild ancestor of corn. 9) The next step in our deductions must now consist in an reversion of our question. We must now explain how we may obtain domesticated corn, starting from a hypothetical wild plant, similar to type c. Of the several changes which must have been necessary to attract the attention of the Indians, the following two seem to me the most important: the disappearance of all abscission layers and the reduction of the glumes. This may have been brought about by an accumulation of mutations. But it seems much more probable to assume that some crossing with a tripsacoid grass or even with Tripsacum australe may have been responsible. In such a cross, the two types of abscission layer would be counterbalanced as shown by the Flhybrids of corn, Tripsacum and Euchlaena. Furthermore in later generations a.tu-allele of Tripsacum may become homozygous and substitute the wild tunicate factor of corn. The hypothesis of a hybrid origin of cultivated corn is not completely new, but has been discussed already by HARSHBERGER and COLLINS. Our hypothesis differs from that of MANGELSDORF and REEVES who assume that crosses with Tripsacum are responsible only for some features of Central and North American corn. 10) The following arguments give indirects evidence in support of our hypothesis: a) Several characters have been observed in indigenous corn from the central region of South America, which may be interpreted as "tripsacoid". b) Equally "zeoid" characters seem to be present in Tripsacum australe of central South-America. c) A system of unbalanced factors, combined by the in-tergeneric cross, may be responsible for the sterility of the wild type tunicata factor when homozygous, a result of the action of modifiers, brought in from Tripsacum together with the tuallele. d) The hybrid theory may explain satisfactorily the presence of so many lethals and semilethals, responsible for the phenomenon of inbreeding in cultivated corn. It must be emphasized that corn does not possess any efficient mechanism to prevent crossing and which could explain the accumulation of these mutants during the evolutionary process. Teosinte which'has about the same mechanism of sexual reproduction has not accumulated such genes, nor self-sterile plants in spite of their pronounced preference for crossing. 11) The second most important step in domestication must have consisted in transforming a four rowed ear into an ear with many rows. The fusion theory, recently revived byLANGHAM is rejected. What happened evidently, just as in succulent pXants (Cactus) or in cones os Gymnosperms, is that there has been a change in phyllotaxy and a symmetry of longitudinal rows superimposed on the original spiral arrangement. 12) The geographical distribution of indigenous corn in South America has been discussed. So far, we may distinguish three zones. The most primitive corn appears in the central lowlands of what I call the Central Triangle of South America: east of the Andies, south of the Amazone-Basin, Northwest of a line formed by the rivers São Prancisco-Paraná and including the Paraguay-Basin. The uniformity of the types found in this extremely large zone is astonishing (BRIEGER and CUTLER). To the west, there is the well known Andian region, characterized by a large number of extremely diverse types from small pop corn to large Cuszco, from soft starch to modified sweet corn, from large cylindrical ears to small round ears, etc.. The third region extends along the atlantic coast in the east, from the Caribean Sea to the Argentine, and is characterized by Cateto, an orange hard flint corn. The Andean types must have been obtained very early, and undoubtedly are the result of the intense Inca agriculture. The Cateto type may be obtained easily by crosses, for instance, of "São Paulo Pointed Pop" to some orange soft corn of the central region. The relation of these three South American zones to Central and North America are not discussed, and it seems essential first to study the intermediate region of Ecuador, Colombia and Venezuela. The geograprical distribution of chromosome knobs is rapidly discussed; but it seems that no conclusions can be drawn before a large number of Tripsacum species has been analysed.

Estudos genéticos sôbre o milho tunicata

The study of pod corn seems still of much importance from different points of view. The phylogenetical importance of the tunicate factor as a wild type relic gene has been recently discussed in much detail by MANGELSDORF and REEVES (1939), and by BRIEGER (1943, 1944a e b). Selection experiments have shown that the pleiotropic effect of the Tu factor can be modified very extensively (BRIEGER 1944a) and some of the forms thus obtained permitt comparison of male and female inflorescences in corn and related grasses. A detailed discussion of the botanical aspect shall be given shortly. The genetic apect, finally, is the subject of the present publication. Pod corn has been obtained twice: São Paulo Pod Corn and Bolivia Pod Corn. The former came from one half ear left in our laboratory by a student and belongs to the type of corn cultivated in the State of São Paulo, while the other belongs to the Andean group, and has been received both through Dr. CARDENAS, President of the University at Cochabamba, Bolivia, and through Dr. H. C. CUTLER, Harvard University, who collected material in the Andes. The results of the studies may be summarized as follows: 1) In both cases, pod corn is characterized by the presence of a dominant Tu factor, localized in the fourth chromosome and linked with sul. The crossover value differs somewhat from the mean value of 29% given by EMERSON, BEADLE and FRAZER (1935) and was 25% in 1217 plants for São Paulo Pod Corn and 36,5% in 345 plants for Bolivia Pod Corn. However not much importance should be attributed to the quantitative differences. 2) Segregation was completely normal in Bolivia Pod Corn while São Paulo Pod Corn proved to be heterozygous for a new com uma eliminação forte, funcionam apenas 8% em vez de 50%. Existem cerca de 30% de "jcrossing-over entre o gen doce (Su/su) e o fator gametofítico; è cerca de 5% entre o gen Tu e o fator gametofítico. A ordem dos gens no cromosômio IV é: Ga4 - Tu - Sul. 3) Using BRIEGER'S formulas (1930, 1937a, 1937b) the following determinations were made. a) the elimination of ga4 pollen tubes may be strong or weak. In the former case only about 8% and in the latter 37% of ga4 pollen tubes function, instead of the 50% expected in normal heterozygotes. b) There is about 30,4% crossing-over between sul and ga4 and 5,3% between Tu and ga3, the order of the factors beeing Su 1 - Tu - Ga4. 4) The new gametophyte factor differs from the two others factors in the same chromosome, causing competition between pollen tubes. The factor Gal, ocupies another locus, considerably to the left of Sul (EMERSON, BEADLE AND FRAZSER, 1935). The gen spl ocupies another locus and causes a difference of the size of the pollen grains, besides an elimination of pollen tubes, while no such differences were observed in the case of the new factor Ga4. 5) It may be mentioned, without entering into a detailed discussion, that it seems remarquable that three of the few gametophyte factors, so far studied in detail are localized in chromosome four. Actuality there are a few more known (BRIEGER, TIDBURY AND TSENG 1938), but only one other has been localized so far, Ga2, in chromosome five between btl and prl. (BRIEGER, 1935). 6) The fourth chromosome of corn seems to contain other pecularities still. MANGELSDORF AND REEVES (1939) concluded that it carries two translocations from Tripsacum chromosomes, and BRIEGER (1944b) suggested that the tu allel may have been introduced from a tripsacoid ancestor in substitution of the wild type gene Tu at the beginning of domestication. Serious disturbances in the segregation of fourth chromosome factors have been observed (BRIEGER, unpublished) in the hybrids of Brazilian corn and Mexican teosinte, caused by gametophytic and possibly zygotic elimination. Future studies must show wether there is any relation between the frequency of factors, causing gametophyte elimination and the presence of regions of chromosomes, tranfered either from Tripsacum or a related species, by translocation or crossing-over.

A ação dos gens gametofíticos com referência especial ao milho

1) The first part deals with the different processes which may complicate Mendelian segregation and which may be classified into three groups, according to BRIEGER (1937b) : a) Instability of genes, b) Abnormal segregation due to distur- bances during the meiotic divisions, c) obscured segregation, after a perfectly normal meiosis, caused by elimination or during the gonophase (gametophyte in higher plants), or during zygophase (sporophyte). Without entering into detail, it is emphasized that all the above mentioned complications in the segregation of some genes may be caused by the action of other genes. Thus in maize, the instability of the Al factor is observed only when the gene dt is presente in the homozygous conditions (RHOADES 1938). In another case, still under observation in Piracicaba, an instability is observed in Mirabilis with regard to two pairs of alleles both controlling flower color. Several cases are known, especially in corn, where recessive genes, when homozigous, affect the course of meiosis, causing asynapsis (asyndesis) (BEADLE AND MC CLINTOCK 1928, BEADLE 1930), sticky chromosomes (BEADLE 1932), supermunmerary divisions (BEADLE 1931). The most extreme case of an obscured segregatiou is represented by the action of the S factors in self stetrile plants. An additional proof of EAST AND MANGELSDORF (1925) genetic formula of self sterility has been contributed by the studies on Jinked factors in Nicotina (BRIEGER AND MANGELSDORF (1926) and Antirrhinum (BRIEGER 1930, 1935), In cases of a incomplete competition and selection between pollen tubes, studies of linked indicator-genes are indispensable in the genetic analysis, since it is impossible to analyse the factors for gametophyte competition by direct aproach. 2) The flower structure of corn is explained, and stated that the particularites of floral biology make maize an excellent object for the study of gametophyte factors. Since only one pollen tube per ovule may accomplish fertilization, the competition is always extremely strong, as compared with other species possessing multi-ovulate ovaries. The lenght of the silk permitts the study of pollen tube competitions over a varying distance. Finally the genetic analysis of grains characters (endosperm and aleoron) simpliflen the experimental work considerably, by allowing the accumulation of large numbers for statistical treatment. 3) The four methods for analyzing the naturing of pollen tube competition are discussed, following BRIEGER (1930). Of these the first three are: a) polinization with a small number of pollen grains, b) polinization at different times and c) cut- ting the style after the faster tubes have passe dand before the slower tubes have reached the point where the stigma will be cut. d) The fourth method, alteration of the distatice over which competition takes place, has been applied largely in corn. The basic conceptions underlying this process, are illustrated in Fig. 3. While BRINK (1925) and MANGELSDORF (1929) applied pollen at different levels on the silks, the remaining authors (JONES, 1922, MANGELSDORF 1929, BRIEGER, at al. 1938) have used a different process. The pollen was applied as usual, after removing the main part of the silks, but the ears were divided transversally into halves or quarters before counting. The experiments showed generally an increase in the intensity of competition when there was increase of the distance over which they had to travel. Only MANGELSDORF found an interesting exception. When the distance became extreme, the initially slower tubes seemed to become finally the faster ones. 4) Methods of genetic and statistical analysis are discussed, following chiefly BRIEGER (1937a and 1937b). A formula is given to determine the intensity of ellimination in three point experiments. 5) The few facts are cited which give some indication about the physiological mechanism of gametophyte competition. They are four in number a) the growth rate depends-only on the action of gametophyte factors; b) there is an interaction between the conductive tissue of the stigma or style and the pollen tubes, mainly in self-sterile plants; c) after self-pollination necrosis starts in the tissue of the stigma, in some orchids after F. MÜLLER (1867); d) in pollon mixtures there is an inhibitory interaction between two types of pollen and the female tissue; Gossypium according to BALLS (1911), KEARNEY 1923, 1928, KEARNEY AND HARRISON (1924). A more complete discussion is found in BRIEGER 1930). 6) A list of the gametophyte factors so far localized in corn is given. CHROMOSOME IV Ga 1 : MANGELSDORF AND JONES (1925), EMERSON 1934). Ga 4 : BRIEGER (1945b). Sp 1 : MANGELSDORF (1931), SINGLETON AND MANGELSDORF (1940), BRIEGER (1945a). CHROMOSOME V Ga 2 : BRIEGER (1937a). CHROMOSOME VI BRIEGER, TIDBURY AND TSENG (1938) found indications of a gametophyte factor altering the segregation of yellow endosperm y1. CHROMOSOME IX Ga 3 : BRIEGER, TIDBURY AND TSENG (1938). While the competition in these six cases is essentially determined by one pair of factors, the degree of elimination may be variable, as shown for Ga2 (BRIEGER, 1937), for Ga4 (BRIEGER 1945a) and for Spl (SINGLETON AND MANGELSDORF 1940, BRIEGER 1945b). The action of a gametophyte factor altering the segregation of waxy (perhaps Ga3) is increased by the presence of the sul factor which thus acts as a modifier (BRINCK AND BURNHAM 1927). A polyfactorial case of gametophyte competition has been found by JONES (1922) and analysed by DEMEREC (1929) in rice pop corn which rejects the pollen tubes of other types of corn. Preference for selfing or for brothers-sister mating and partial elimination of other pollen tubes has been described by BRIEGER (1936). 7) HARLAND'S (1943) very ingenious idea is discussed to use pollen tube factors in applied genetics in order to build up an obstacle to natural crossing as a consequence of the rapid pollen tube growth after selfing. Unfortunately, HARLAND could not obtain the experimental proof of the praticability of his idea, during his experiments on selection for minor modifiers for pollen tube grouth in cotton. In maize it should be possible to employ gametophyte factors to build up lines with preference for crossing, though the method should hardly be of any practical advantage.

Convection and segregation of beads in a flat rotating box

Magdeburg, Univ., Fak. für Naturwiss., Diss., 2012

Sozialräumliche Segregation : Führt die sozialräumliche Segregation zu einer Vererbung von Armut?

[s.c.]

mRNA metabolism: nonsense mediated mRNA decay as a tool for gene therapy and the role of human DIS3L2 in transcript degradation

Tese de mestrado em Biologia Humana e Ambiente, apresentada à Universidade de Lisboa, através da Faculdade de Ciências, 2015

Ecomorphology and diet reflect the spatial segregation between two Siluriformes species inhabiting a stream of the Bodoquena Plateau, in Central Brazil

Pimelodella taenioptera Miranda Ribeiro, 1914 and Imparfinis schubarti (Gomes, 1956) are two of the most common fish species in Bodoquena Plateau streams, Paraguay basin. These species have benthic habits and subaquatical observations suggested that they present differentiation in their preference for mesohabitat types. Pimelodella taenioptera shows preference for slow waters, such as pools, while I. schubarti is associated to riffles. In this study we investigated if the known patterns of mesohabitat use of P. taenioptera and I. schubarti can be predict by their ecomorphological and trophic traits. We described the dietary habits and ecomorphological attributes of P. taenioptera and I. schubarti individuals, captured in the Parque Nacional da Serra da Bodoquena (PNSB), Mato Grosso do Sul state, central Brazil. Pimelodella taenioptera presented a more generalist diet, consuming a total of 23 different food items. Imparfinis schubarti have a diet based exclusively on aquatic insects. The ecomorphological analysis revealed that the species differed in relation to five morphological traits associated to habitat use (p <0.01). The results of this study reveal a clear functional dissimilarity between P. taenioptera and I. shubarti. The observed trophic and ecomorphological patterns are congruent with the known habitat use for these species and probably reflect the spatial and temporal variability on conditions and resources present in riffles and pools. Therefore, as expected, the morphological and feeding attributes represent predictive information related to mesohabitat use.

Thickening of phase change materials (PCM) to avoid segregation

Estudi elaborat a partir d’una estada a Çukurova University, Turquia, al juliol del 2006. L’emmagatzematge d’energia tèrmica ha atret interès en aplicacions tèrmiques com l’aigua calenta, la calefacció i l’aire condicionat. Aquests sistemes són útils per corregir la no coincidència entre la oferta i la demanda d’energia. Principalment hi ha dos tipus de sistemes d’emmagatzematge d’energia tèrmica, emmagatzematge amb calor sensible i amb calor latent. L’emmagatzematge amb calor latent és particularment atractiu degut a la seva habilitat de donar una densitat d’emmagatzematge d’energia més alt i la seva característica d’emmagatzemar calor a una temperatura constant corresponent a la temperatura de transició de fase de la substància emmagatzemadora de calor. Les salts hidratades orgàniques tenen certes avantatges com a materials d’emmagatzematge de calor latent sobre els materials orgànics. En canvi, quan les salts hidratades s’utilitzen com a materials de canvi de fase (PCM) apareixen alguns problemes en les aplicacions d’emmagatzematge de calor latent. Aquests són el subrefredament de les salts hidratades quan es congelen degut a les seves dèbils propietats de nucleació, i la separació de fase que hi apareix degut a una fusió incongruent. En aquest estudi, s’estabilitza sal de Glauber (Na2SO4.10H2O) amb diferents concentracions de poliacrilamida i gelatina per prevenir la fusió incongruent. Per prevenir el subrefredament s’utilitza un agent nucleant amb una estructura cristal•lina semblant a la de la sal de Glauber. La capacitat d’emmagatzematge de calor de les mostres de PCM estabilitzades amb diferents concentracions de gels polimèrics es determinen amb DCS i amb el mètode T-history.

Transferring QTL technology to the pig breeding industry (PigQTech) - a demonstration project

The aim of the project has been to demonstrate how the farm animal breeding industry can utilise gene mapping technology to accelerate genetic improvement. Previous theoretical studies had suggested that the use of marker assisted selection could potentially increase the annual improvement for quantitative traits like backfat with about 10% and for more difficult traits such as meat quality and reproduction by as much as 40-60% compared with existing technology. The work has comprised two major tasks: 1. Commercially relevant populations have been screened for segregation at QTLs identified in experimental populations. The aim has been to establish optimal strategies for QTL detection in commercial pig populations and the extent to which QTLs explaining major phenotypic differences between divergent lines used in experimental studies also explain quantitative variation within commercial lines. The results are important for specifying future strategies for finding economically valuable QTLs. 2. Marker assisted backcrossing has been used to demonstrate how a QTL allele can be introgressed from one breed to another. The work has focused on the major fatness QTL on pig chromosome 4 previously identified in a wild pig/Large White intercross. The end result was not designed to be a commercially viable product in its own right, but the process has validated a number of points of major importance for the exploitation of QTLs in livestock.

Changes in reproductive roles are associated with changes in gene expression in fire ant queens.

Abstract In species with social hierarchies, the death of dominant individuals typically upheaves the social hierarchy and provides an opportunity for subordinate individuals to become reproductives. Such a phenomenon occurs in the monogyne form of the fire ant, Solenopsis invicta, where colonies typically contain a single wingless reproductive queen, thousands of workers and hundreds of winged nonreproductive virgin queens. Upon the death of the mother queen, many virgin queens shed their wings and initiate reproductive development instead of departing on a mating flight. Workers progressively execute almost all of them over the following weeks. To identify the molecular changes that occur in virgin queens as they perceive the loss of their mother queen and begin to compete for reproductive dominance, we collected virgin queens before the loss of their mother queen, 6 h after orphaning and 24 h after orphaning. Their RNA was extracted and hybridized against microarrays to examine the expression levels of approximately 10 000 genes. We identified 297 genes that were consistently differentially expressed after orphaning. These include genes that are putatively involved in the signalling and onset of reproductive development, as well as genes underlying major physiological changes in the young queens.

Proteomic and Metabolomic Analyses of Mitochondrial Complex I-deficient Mouse Model Generated by Spontaneous B2 Short Interspersed Nuclear Element (SINE) Insertion into NADH Dehydrogenase (Ubiquinone) Fe-S Protein 4 (Ndufs4) Gene.

Eukaryotic cells generate energy in the form of ATP, through a network of mitochondrial complexes and electron carriers known as the oxidative phosphorylation system. In mammals, mitochondrial complex I (CI) is the largest component of this system, comprising 45 different subunits encoded by mitochondrial and nuclear DNA. Humans diagnosed with mutations in the gene NDUFS4, encoding a nuclear DNA-encoded subunit of CI (NADH dehydrogenase ubiquinone Fe-S protein 4), typically suffer from Leigh syndrome, a neurodegenerative disease with onset in infancy or early childhood. Mitochondria from NDUFS4 patients usually lack detectable NDUFS4 protein and show a CI stability/assembly defect. Here, we describe a recessive mouse phenotype caused by the insertion of a transposable element into Ndufs4, identified by a novel combined linkage and expression analysis. Designated Ndufs4(fky), the mutation leads to aberrant transcript splicing and absence of NDUFS4 protein in all tissues tested of homozygous mice. Physical and behavioral symptoms displayed by Ndufs4(fky/fky) mice include temporary fur loss, growth retardation, unsteady gait, and abnormal body posture when suspended by the tail. Analysis of CI in Ndufs4(fky/fky) mice using blue native PAGE revealed the presence of a faster migrating crippled complex. This crippled CI was shown to lack subunits of the "N assembly module", which contains the NADH binding site, but contained two assembly factors not present in intact CI. Metabolomic analysis of the blood by tandem mass spectrometry showed increased hydroxyacylcarnitine species, implying that the CI defect leads to an imbalanced NADH/NAD(+) ratio that inhibits mitochondrial fatty acid β-oxidation.

IFN stimulated gene expression in the liver is a better predictor of treatment response in chronic hepatitis c than the IL28b (IFN lambda 3) genotype

Background: Therapy of chronic hepatitis C (CHC) with pegIFNa/ribavirin achieves sustained virologic response (SVR) in ~55%. Pre-activation of the endogenous interferon system in the liver is associated non-response (NR). Recently, genome-wide association studies described associations of allelic variants near the IL28B (IFNλ3) gene with treatment response and with spontaneous clearance of the virus. We investigated if the IL28B genotype determines the constitutive expression of IFN stimulated genes (ISGs) in the liver of patients with CHC. Methods: We genotyped 93 patients with CHC for 3 IL28B single nucleotide polymorphisms (SNPs, rs12979860, rs8099917, rs12980275), extracted RNA from their liver biopsies and quantified the expression of IL28B and of 8 previously identified classifier genes which discriminate between SVR and NR (IFI44L, RSAD2, ISG15, IFI22, LAMP3, OAS3, LGALS3BP and HTATIP2). Decision tree ensembles in the form of a random forest classifier were used to calculate the relative predictive power of these different variables in a multivariate analysis. Results: The minor IL28B allele (bad risk for treatment response) was significantly associated with increased expression of ISGs, and, unexpectedly, with decreased expression of IL28B. Stratification of the patients into SVR and NR revealed that ISG expression was conditionally independent from the IL28B genotype, i.e. there was an increased expression of ISGs in NR compared to SVR irrespective of the IL28B genotype. The random forest feature score (RFFS) identified IFI27 (RFFS = 2.93), RSAD2 (1.88) and HTATIP2 (1.50) expression and the HCV genotype (1.62) as the strongest predictors of treatment response. ROC curves of the IL28B SNPs showed an AUC of 0.66 with an error rate (ERR) of 0.38. A classifier with the 3 best classifying genes showed an excellent test performance with an AUC of 0.94 and ERR of 0.15. The addition of IL28B genotype information did not improve the predictive power of the 3-gene classifier. Conclusions: IL28B genotype and hepatic ISG expression are conditionally independent predictors of treatment response in CHC. There is no direct link between altered IFNλ3 expression and pre-activation of the endogenous system in the liver. Hepatic ISG expression is by far the better predictor for treatment response than IL28B genotype.