Molecular mechanisms of determination in Drosophila

A number of Drosophila proteins have been identified that play key roles in the establishment of active or inactive states of selector gene expression. Interactions between these proteins and their target selector genes are beginning to be understood, shaping our molecular view as to how stable determination of cells is achieved.     

Tracking the contribution of inductive bias to individualised internal models

Internal models capture the regularities of the environment and are central to understanding how humans adapt to environmental statistics. In general, the correct internal model is unknown to observers, instead they rely on an approximate model that is continually adapted throughout learning. However, experimenters assume an ideal observer model, which captures stimulus structure but ignores the diverging hypotheses that humans form during learning. We combine non-parametric Bayesian methods and probabilistic programming to infer rich and dynamic individualised internal models from response times. We demonstrate that the approach is capable of characterizing the discrepancy between the internal model maintained by individuals and the ideal observer model and to track the evolution of the contribution of the ideal observer model to the internal model throughout training. In particular, in an implicit visuomotor sequence learning task the identified discrepancy revealed an inductive bias that was consistent across individuals but varied in strength and persistence.     

Comparative study between the free radicals and tumor markers in patients with gastrointestinal tumors

The tumorous processes, increased level of tumor markers and the change of free radical status are associated in patents with gastrointestinal tumors. The aim of this study was to examine free radical status and tumor markers in patients with gastrointestinal tumors. Two hundered and thirteen patients with gastrointestinal tumor were examined. In the control group 44 non-tumorous patients were examined. The tumor markers (CEA, CA 19-9, CA 72-4, AFP, TPA, AGP) and free radical status (total scavenger capacity) were diagnosed using venal blood (obtained by LIA-kits and chemiluminescent methods, LIA-mAT and the Lumat Berthold instrument). It has been found that: (1) The results showed that the tumor markers, TPA and AGP are the best indicators for the tumorous process; (2) The AGP serum level was in the operable case 91.56+/-38.29 mg/dl meanwhile its value was, 128.46+/-47.62 mg/dl (P<0.001) in the inoperable case; and (3) The TPA value was 118.37+/-155.47 mg/dl in the operable case, (P<0.001) while its value was 227.32+/-244.39 mg/dl in inoperable cases. The significantly high levels of the plasma Chemiluminescent Light Intensity (CLI)=28.12+/-25.96; was obtained in patients with rectal tumors vs. in the control cases CLI= 4.27+/-5.12 RLU% (Relative Light Unit; mean+S.D.; P<0.005). In six of these cases, the free radical status examination indicated the presence of the tumor, even though the level of tumor markers was normal. It has been concluded that the testing of both regular tumor markers and free radical status has an important role in the diagnosis and monitoring of the patients with gastrointestinal tumors.     

Population genomics of the raccoon dog (<Emphasis Type="Italic">Nyctereutes procyonoides</Emphasis>) in Denmark: insights into invasion history and population development

The raccoon dog (Nyctereutes procyonoides) has a wide distribution in Europe and is a prominent example of a highly adaptable alien species. It has been recorded sporadically in Denmark since 1980 but observations since 2008 suggested that the species had established a free-ranging, self-sustaining population. To elucidate the origin and genetic patterns of Danish raccoon dogs, we studied the population genomics of 190 individuals collected in Denmark (n = 141) together with reference captive individuals from Poland (n = 21) and feral individuals from different European localities (Germany, Poland, Estonia and Finland, n = 28). We used a novel genotyping-by-sequencing approach simultaneously identifying and genotyping a large panel of single nucleotide polymorphisms (n = 4526). Overall, there was significant indication for contemporary genetic structuring of the analysed raccoon dog populations, into at least four different clusters, in spite of the existence of long distance gene flow and secondary admixture from different population sources. The Danish population was characterized by a high level of genetic admixture with neighbouring feral European ancestries and the presence of private clusters, non-retrieved in any other feral or captive populations sampled. These results suggested that the raccoon dog population in Denmark was founded by escapees from genetically unidentified Danish captive stocks, followed by a recent admixture with individuals migrating from neighbouring Germany.     

Unusual sialilation of three different rare genetic variants of serum DBP: Gc 1A17, Gc 1A16, and Gc 1A11

Summary The proteins of three anodal Gc1 variants, Gc 1A16, 1A11, and 1A17, are characterized by the most acidic isoelectric points observed so far among the different Gc mutants. Stepwise removal of N-acetylneuraminic acid (NANA) by treatment with neuraminidase was performed to estimate the degree of sialilation of these Gc variants. The results indicate that both proteins, the anodal and the cathodal component of these Gc 1 mutants, carry sialic acid residues. This observation is remarkable in so far as usually only the anodal component of the Gc 1 protein contains NANA and only a single residue. From the experiments carried out it can be deduced that Gc 1A16 has two NANA residues in the anodal and one NANA residue in the cathodal component. Gc 1A16 was found in four members of three generations in a Danish family; the variant segregated as a Mendelian trait. More difficult to interprete are the results obtained with the variants Gc 1A11 and Gc 1A17. Gc 1A11 probably has three NANA residues in the anodal and two NANA residues in the cathodal component. Gc 1A11 has been observed in two mother-child pairs and is presumably also a simple genetic trait. Gc 1A17 has also several NANA residues in both Gc proteins; it is suggested that the anodal component has either three or four NANA residues and the cathodal component either two or three NANA residues. Family information on this variant is not yet available.     

Sexual dimorphism in rat left atrial function and response to adrenergic stimulation

A number of investigations in humans and animals suggest that there may be intrinsic sex-associated differences in cardiac function. Using left atrial preparations from male and female rat hearts, we examined differences in myocardial function and response to adrenergic agonists. Contractile parameters were measured in isolated atria by conventional isometric methods in the absence or presence of isoproterenol or phenylephrine. Responsiveness to Ca²⁺ was measured in detergent-skinned atrial fibers and actomyosin ATPase activity was measured in isolated myofibrils. Tetanic contractions were generated by treating the atrium with ryanodine followed by high frequency stimulation. Developed force was greater and maximal rates of contraction and relaxation were more rapid in the female atrium. The relationship between Ca²⁺ concentration and force in both intact atria and detergent-skinned atrial fibers in females fell to the left of that for males. At low Ca²⁺ concentrations, skinned fibers from female atria generated more force and myofibrils from female atria had higher myosin ATPase activity than males. Tetanic contraction in the presence of high extracellular Ca²⁺ was greater in female atria. Male atrium had larger inotropic responses to isoproterenol and to phenylephrine, but drug-elicited cAMP and inositol phosphate production did not differ between sexes. The results demonstrate sex-related differences in atrial function that can be partially explained by greater myofibrillar Ca²⁺-sensitivity in females. A potential contribution of sarcolemmal Ca2+ influx is suggested by greater tetanic contraction in ryanodine-treated female atrium. The larger response of males to adrenergic stimulation does not appear to be explained by higher production of relevant second messengers. Future studies will investigate the role of sex hormones in these sexually dimorphic responses and may indicate a need for gender-specific therapeutic interventions for myocardial dysfunction.     

Condensation of interphase chromatin in nuclei of synchronized chinese hamster ovary (CHO-K1) cells

Reversibly permeabilized cells have been used to visualize interphase chromatin structures in the presence and absence of biotinylated nucleotides. By reversing permeabilization, it was possible to confirm the existence of a flexible chromatin folding pattern through a series of transient geometric forms such as supercoiled, circular forms, chromatin bodies, thin and thick fibers, and elongated chromosomes. Our results show that the incorporation of biotin-11-dUTP interferes with chromatin condensation, leading to the accumulation of decondensed chromatin structures. Chromatin condensation without nucleotide incorporation was also studied in cell populations synchronized by centrifugal elutriation. After reversal of permeabilization, nuclei were isolated and chromatin structures were visualized after DAPI staining by fluorescent microscopy. Decondensed veil-like structures were observed in the early S phase (at an average C-value of 2.21), supercoiled chromatin later in the early S (2, 55 C), fibrous structures in the early mid S phase (2, 76 C), ribboned structures in the mid-S phase (2, 98 C), continuous chromatin strings later in the mid-S phase (3,28), elongated prechromosomes in the late S-phase (3, 72 C), precondensed chromosomes at the end and after the S phase (3, 99 C). Fluorescent microscopy revealed that neither interphase nor metaphase chromosomes are separate entities but form a linear array arranged in a semicircle. Linear arrangement was confirmed by computer image analysis.     

Higher-Order Looping and Nuclear Organization of Tcra Facilitate Targeted RAG Cleavage and Regulated Rearrangement in Recombination Centers

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Highlights? RAG-dependent monoallelic loop formation is linked to monoallelic RAG cleavage ? RAG enrichment, cleavage, and higher-order loop formation occur at the 3′ end of Tcra ? Looping out is a determinant of directed RAG targeting ? ATM-mediated control of looping out is linked to the maintenance of genome stability     

Modelled population growth based on reproduction differs from life tables based on age determination in Danish raccoon dogs ( Nyctereutes procyonoides )

The population of raccoon dogs (Nyctereutes procyonoides) in Denmark has increased rapidly from 1995 when the first was recorded until today where 3291 raccoon dogs are trapped, shot by hunters or road killed. The aims of this study are to present the first data on reproduction and life tables of raccoon dogs in Denmark and to compare mortality from modelled life tables with game bag records and sampled raccoon dogs in different age groups. In this study, the uteri of 89 adult females (> 10 months) were examined for placental scars (PSC), and 561 individuals (289 males, 272 females) were aged using pulp cavity width and dental lines in canine teeth. The litter size of raccoon dogs in Denmark is to date the largest litter size recorded in the wild (mean ± SE) 10.8 ± 0.4, range 1–16 pubs and fecundity 8.4 ± 0.6 pubs. The percent-reproducing females are 78–83%, based on dark and all PSC, respectively. A significant difference was found between the proportion of individuals composing the different age groups based on age determination of individuals collected (Ntage) and the modelled number of individuals in age groups based on fecundity and different mortality rate (Ntmodel), X2 = 8, p < 0.05. The discrepancy between the relatively high reproduction and lifetables may be due to older and more experienced animals that avoid culling. A low population density in a newly founded Danish population of raccoon dogs, together with a milder climate where raccoon dogs can forage during the winter, may cause an exceptionally high reproduction in Danish raccoon dogs.