Incompletely base-paired flip-flop terminal loops link the two DNA strands of the vaccinia virus genome into one uninterrupted polynucleotide chain

The nature of the ends of the vaccinia virus genome was determined by nucleotide sequencing. Our finding of terminal hairpins indicated that the linear double-stranded DNA molecule consists of a single continuous polynucleotide chain. The 104 nucleotide apex of the hairpin contains predominantly A and T residues and is incompletely base-paired. These loops exist in two forms, which when inverted with respect to each other are complementary in sequence. Both forms of the 104 nucleotide loop are present in nearly equimolar amounts at each end of the genome. A set of 13 tandem 70 bp repeats begins 87 bp from the proximal segment of the terminal loop, followed by a unique sequence of 325 bp, and then by a second set of 18 tandem 70 bp repeats. The sequence of the 70 bp repeats reveals a 13 bp internal redundancy. Self-priming and de novo start replication models, which involve a site-specific nick in one DNA strand proximal to the 104 nucleotide loop, account for the observed sequence inversions and incomplete base-pairing. Similar mechanisms may be involved in replication of the ends of the eucaryotic chromosome.     

Modelling prey-predator cycles using hemipteran predators of mosquito larvae for reducing world-wide mosquito-borne disease incidence

Diplonychus indicus is an aquatic hemipterous bug known to be a voracious predator of dipteran larvae, among others, and to show a selective predation for mosquito larvae when exposed to a mixed prey diet. A datum consisted of the percentage of the fourth instar of (25) culicine mosquitoes killed by the bug. Data around the clock, published earlier (from starved adult males of this bug), reanalyzed by single cosinor, reveal a circasemidian rhythm (p = 0.004). This result prompts the recommendation of studying the time structure of prey-predator cycles further to evaluate the merits or demerits of introducing the bug in the field with the aim of reducing worldwide mosquito-borne disease incidence.     

Cyclic cystine knot and its strong implication on the structure and dynamics of cyclotides

The archetypal Viola odorata cyclotide cycloviolacin-O1 and its seven analogs, created by partial or total reduction of the three native S–S linkages belonging to the “cyclic cystine knot” (CCK) motif are studied for their structural and dynamical diversities using molecular dynamics simulations. The results indicate interesting interplay between the constraints imposed by the S–S bonds on the dynamical modes and the corresponding structure of the model peptide. Principal component analysis brings out the variation in the extent of dynamical freedom along the peptide backbone for each model. The motions are characterized by low amplitude diffusive modes in the peptides retaining most of the native S–S linkages in contrast to the large amplitude discrete jumps where at least two or all of the three S–S linkages are reduced. Simulation results further indicate that the disulfide bond between Cys1–18 is formed at a much faster pace compared with its two other peers Cys5–20 and Cys10–25 as found in the native peptide. This gives insight as to why the S–S linkages appear in the native peptide in a particular combination. Model therapeutics and drug delivery engines can potentially utilize this information to customize the engineered S–S bonds and gauge its impact on the dynamic flexibility of a model macrocyclic peptide.     

Activation of multiple cancer pathways and tumor maintenance function of the 3q amplified oncogene FNDC3B

FNDC3B was recently identified in an oncogenomic screen for amplified oncogenes in hepatocellular carcinoma. It is located at 3q26 and is amplified in over 20% of cancers, usually as part of a broad amplified region encompassing the entire 3q arm. Consistent with an oncogenic role in multiple cancer types, we show here that overexpression of FNDC3B is capable of malignantly transforming mammary and kidney epithelial cells in addition to hepatocytes. To explore how FNDC3B transforms cells, we determined the cellular localization of its gene product and the cancer pathways that it activates. We found that the FNDC3B oncoprotein localizes to the Golgi network, and that its correct localization is essential for its transforming function. We found that overexpression of FNDC3B induces the epithelial-to-mesenchymal transition (EMT) and activates several cancer pathways, including PI3-kinase/Akt, Rb1 and TGFβ signaling. For TGFβ signaling, we analyzed the point in the pathway at which FNDC3B operates and obtained evidence that it induces expression of all three TGFβ ligands and also promotes TGFBR1 cell-surface localization. We found that RNAi-mediated knockdown of FNDC3B in cancer cells with 3q amplification suppressed their clonogenicity and tumorigenicity, but that the same RNAi knockdown had no effect on single-copy 3q cancer cells. These results indicate that FNDC3B is an important oncogenic driver gene of the 3q amplicon, adding to the growing list of oncogenic drivers within this commonly amplified region.     

The effect of the accumulation of disease resistance genes on the long-term association of a global sample of environments for testing spring bread wheat

CIMMYT (the International Maize and Wheat Improvement Center) has routinely conducted international wheat yield trials to study the adaptation of spring bread wheat. The first of these, the International Spring Wheat Yield Nursery (ISWYN), was conducted for 31 years from 1964 to 1994 inclusive (30 cycles were conducted as no nursery was distributed in 1993 because of Karnal Bunt). Recently, pattern analysis methods have been developed and a set of computer programs written, which enable retrospective analyses of such historical databases to appraise the relationships among test environments in a way that discriminates among genotypes. Such an analysis was conducted on the 30 years of yield data from ISWYN and the classification derived from these analyses was compared with an agroecological classification of spring wheat test environments derived by CIMMYT. The incidence of foliar diseases (stem rust, leaf rust, yellow rust, Septoria spp. and Fusarium spp.) was important in the distinction between the high-rainfall low-latitude (mega-environment 2) and the high-input-irrigated low-latitude (mega-environment 1) environment types. The accumulation of resistance genes for these diseases has been an objective of the CIMMYT wheat breeding program. It was hypothesized that, as the relevant resistance genes were successfully pyramided into the germplasm, the distinction between these two mega-environment types would disappear. The results of the retrospective analyses support this hypothesis. Received: 19 May 1999 / Accepted: 17 January 2000     

Distribution of Clostridium perfringens and Fecal Sterols in a Benthic Coastal Marine Environment Influenced by the Sewage Outfall from McMurdo Station, Antarctica

The spatial distribution, movement, and impact of the untreated wastewater outfall from McMurdo Station, Antarctica, were investigated under early austral summer conditions. The benthic environment was examined to determine the distribution of Clostridium perfringens in sediment cores and the intestinal contents of native invertebrates and fish along a transect of stations. These stations extended ca. 411 m south of the outfall. The findings revealed that the concentration of C. perfringens decreased with depth in the sediment and distance from the outfall. High percentages of tunicates and sea urchins were colonized with this bacterium along the transect. Coprostanol concentrations were also measured in sediment samples taken from each of the transect stations, and a similar trend was observed. These results are in agreement with the findings of previous studies performed with the water column and collectively provide evidence that the disposal of domestic wastes deserves special consideration in polar marine environments.     

Glycolysis regulates Hedgehog signalling via the plasma membrane potential

The authors regret omitting the citation of a bioRxiv preprint study by preprint: Emmons‐Bell et al (2020), who independently discovered the role of ion channel‐dependent membrane depolarization for Smo membrane accumulation in the fly wing disc. This study used a different methodological approach and did not describe the mechanism of how membrane potential affects hedgehog signaling. The reference is herewith added.     

Insulin secretion and action in the hyperthyroid rat

To gain insight into the mechanism of the altered carbohydrate metabolism in thyrotoxicosis, intravenous glucose tolerance tests (IVGTT) and pancreatic suppression tests (PST) were performed in hyperthyroid rats (0.1 mg/kg T4 X 5 days) to assess insulin secretion and action in vivo. Thyroid hormone injections significantly increased T4 levels (182.8 nM +/- 11.6 (SEM) versus 50.2 +/- 6.4; P less than 0.001) and baseline glucose concentrations (9.3 mM +/- 0.2 versus 7.1 +/- 0.2; P less than 0.001). Body weights, basal insulin concentrations, glucose concentrations during IVGTT, glucose disappearance rates and steady state plasma glucose levels (SSPG) were normal. Insulin concentrations during the glucose tolerance test and during the PST were significantly decreased. The metabolic clearance rate of insulin (ml/min/kg +/- SEM) was significantly (P less than 0.01) increased (54.4 +/- 3.5 versus 41.6 +/- 2.3) in the hyperthyroid rats. If the different baseline glucose values were subtracted from the glucose concentrations achieved during the 2 tests, both the glucose disappearance rate and the fall in SSPG levels were significantly enhanced in the T4-injected animals. Thus, in the hyperthyroid rat, insulin secretion is decreased, the clearance of insulin is increased and insulin sensitivity is either normal or possibly enhanced.