The SRM12/ADA1 Gene Sequence Inserted into Recombinant Plasmids Makes Them More Mitotically Stable in Budding Yeast Cells

TheSRM12/ADA1 gene sequence inserted into a recombinant circular plasmid improves its maintenance in budding yeast (Saccharomyces cerevisiae) cells. Plasmid stabilization caused by the integrated SRM12 sequence does not require the SRM12 function complementing the srm12 mutation and depends on the orientation of the inserted sequence in the vector. This stabilization is mainly due to a decrease in spontaneous plasmid underreplication/copy loss rather than an increase in the fidelity of mitotic plasmid segregation.     

Genetic analysis of mitochondrial rho-mutability in Saccharomyces. IV. Relation between spontaneous rho-mutability and mitotic stability in disomic Saccharomyces cerevisiae

In the yeast Saccharomyces cerevisiae the disomy for chromosome XIV resembles the previously described disomy for chromosome IV in that it leads to a significant decrease in spontaneous rho- mutability. The nuclear srm1 mutation, reducing spontaneous rho- mutability, diminishes significantly the mitotic disome stability. So, the mechanisms of spontaneous rho- mutagenesis and mitotic disome stability seem to compete for the function affected by the srm1 mutation.     

Covalent stabilization of the nontransformed chick oviduct cytosol progesterone receptor by chemical cross-linking

The nontransformed forms of the chick oviduct cytosol progesterone receptor of sedimentation coefficient approximately 8 S (8S-PR) are heterooligomers including one hormone binding molecule, either B, approximately 110,000, or A, approximately 79,000, and two non-hormone binding subunits recently identified as heat-shock protein Mr approximately 90,000 (hsp 90) [Renoir, J. M., Buchou, T., Mester, J., Radanyi, C., & Baulieu, E. E. (1984) Biochemistry 23, 6016-6023]. In the crude cytosol, bisimidates reacted under mild conditions and gave rise to complexes, binding progesterone and reacting with BF4, an anti-hsp 90 monoclonal antibody. These complexes have a sedimentation coefficient of 8.4 S and Rs of 8.1 nm in the presence of 0.4 M KCl and in the absence of molybdate ions, i.e., in conditions that would transform non-cross-linked 8S-PR to Rs approximately 5 nm forms of approximately 4-S sedimentation coefficient. All bisimidates tested, of an effective reagent length between 0.73 and 1.09 nm, gave comparable results in the cytosol prepared with or without molybdate ions, confirming that the latter were not responsible for the formation of the cross-linked 8S complexes. It was found that the dimethyl pimelimidate cross-linked 8S-PR was more resistant to inactivating conditions, urea, or heat treatment than the non-cross-linked 8S-PR. The 8S-PR cross-linked in the cytosol was purified by affinity chromatography in the absence of molybdate ions. After purification, it also reacted with the monoclonal antibody BF4 and had the same Rs (8.0 nm), sedimentation coefficient (approximately 8.5 S), and thus Mr (approximately 290,000) as the original cytosol.(ABSTRACT TRUNCATED AT 250 WORDS)     

Bidentate peptides: highly potent new inhibitors of enkephalin degrading enzymes

Three series of bidentates bearing an hydroxamic or an N-Acyl-N-hydroxy amino group on structures related to Phe-Gly or Phe-Ala exhibit strong inhibitory potency against purified enkephalinase with IC50 values in the 4 to 15 nM range. As with thiol-containing inhibitors, such as thiorphan, the most active compounds are those in which a methylene spacer separates the benzyl P1' moiety from the Zn coordinating residue. Formation of a bidentate complex with the metal enzyme is clearly demonstrated by a loss of potency of three order of magnitude following the removal of one component of the bidentate group. All the compounds studied are unable to interact with angiotensin converting enzyme (IC50 greater than 10,000 nM). Moreover, compounds of the general formula HONHCO-CH2-CH(CH2 phi)-CONH-CH(R)-COOH belonging to the most active series of enkephalinase blockers (IC50 approximately 4 nM) behave also as highly potent and competitive inhibitors (IC50 approximately 10 nM) of a Tyr-Gly releasing dipeptidylaminopeptidase purified from rat brain. The pure steroisomer [(R)-3-(N-hydroxy)carboxamido-2-benzylpropanoyl]-L-alanine designated kelatorphan, exhibits also a relatively good inhibitory potency against aminopeptidases (IC50 approximately 10 microM) and can be considered as the first virtually complete inhibitor of enkephalin metabolism. This very interesting property of inhibiting all three enzymes of enkephalin metabolism could enhance the required selectivity for a possible clinical use of these inhibitors as new analgesic and psychoactive drugs.     

Effect of radiotherapy and chemoradiotherapy on circulating antioxidant system of human uterine cervical carcinoma

Rats bearing the Yoshida AH-130 ascites hepatoma showed important changes in lipid metabolism. The presence of this rapidly growing tumour induced a significant reduction in the intestinal absorption of an oral [^l4C]triolein load but without changes in whole body oxidation of the tracer to CO₃. Both white (WAT) and brown (BAT) adipose tissue lipoprotein lipase (LPL) activities were increased at day 4 of tumour growth, changes that seem to be related with those observed in [¹⁴C] lipid accumulation; however, heart LPL activity was increased at day 7 but there was no change at day 4. In addition, there was a marked hyperlipemia in the tumour-bearing animals, whereas the blood ketone body concentrations were lower in these animals in comparison with the corresponding pair-fed group. The in vivo lipogenic rate was increased in liver of the tumour-bearing animals (day 4); conversely, it was decreased in WAT and skeletal muscle (day 4) and IBAT (day 7) of the AH-130-bearing rats. It may be suggested that the increased liver lipogenic rate associated with tumour burden is the main factor contributing to the hyperlipidaemia present in the Yoshida AH-130 bearing rats.     

Extracellular matrix components and proteolytic enzymes in uterine cervical carcinoma

The important components of mucopolysaccharides and collagen have been analyzed in tissues of control and carcinoma of uterine cervix. Among these components hyaluronic acid and chondroitin sulphate levels were found to be increased, whereas decreased level of collagen was observed in uterine cervical carcinoma. Serum cathepsin B, D and acid and alkaline phosphatases have also been analyzed in controls and carcinoma patients before and after treatments. The activities of these enzymes have been found to increase prominently in advanced stages. Among these enzymes cathepsin B and alkaline phosphatase have exhibited remarkable increase in activity in uterine cervical carcinoma. Different modes of treatment exerted reversion of the elevated activities of these enzymes. However, combined therapy type II (radiation combined with cisplatin and cyclophosphomide) seems to be more effective in reverting the activities of these enzymes to normal levels.     

A Plasmodium homolog of ER tubule-forming proteins is required for parasite virulence

Reticulon and REEP family of proteins stabilize the high curvature of endoplasmic reticulum (ER) tubules. Plasmodium berghei Yop1 (PbYop1) is a REEP5 homolog in Plasmodium. Here, we characterize its function using a gene-knockout (Pbyop1∆). Pbyop1∆ asexual stage parasites display abnormal ER architecture and an enlarged digestive vacuole. The erythrocytic cycle of Pbyop1∆ parasites is severely attenuated and the incidence of experimental cerebral malaria is significantly decreased in Pbyop1∆-infected mice. Pbyop1∆ sporozoites have reduced speed, are slower to invade host cells but give rise to equal numbers of infected HepG2 cells, as WT sporozoites. We propose that PbYOP1’s disruption may lead to defects in trafficking and secretion of a subset of proteins required for parasite development and invasion of erythrocytes. Furthermore, the maintenance of ER morphology in different parasite stages is likely to depend on different proteins.     

Modeling Cumulative Effects of Climate and Development on Moose,Wolf, and Caribou Populations

Wildlife models focused solely on a single strong influence (e.g., habitat components, wildlife harvest) are limited in their ability to detect key mechanisms influencing population change. Instead, we propose integrated modeling in the context of cumulative effects assessment using multispecies population dynamics models linked to landscape-climate simulation at large spatial and temporal scales. We developed an integrated landscape and population simulation model using ALCES Online as the model-building platform, and the model accounted for key ecological components and relationships among moose (Alces alces), grey wolves (Canis lupus nubilus), and woodland caribou (Rangifer tarandus caribou) in northern Ontario, Canada. We simulated multiple scenarios over 5 decades (beginning 2020) to explore sensitivity to climate change and land use and assessed effects at multiple scales. The magnitude of effect and the relative importance of key factors (climate change, roads, and habitat) differed depending on the scale of assessment. Across the full extent of the study area (654,311km² [ecozonal scale]), the caribou population declined by 26% largely because of climate change and associated predator-prey response, which led to caribou range recession in the southern part of the study area. At the caribou range scale (108,378 km²), which focused on 2 herds in the northern part of the study area, climate change led to a 10% decline in the population and development led to an additional 7% decline. At the project scale (8,331 km²), which was focused more narrowly on the landscape surrounding 4 proposed mines, the caribou population declined by 29% largely in response to simulated development. Given that observed caribou population dynamics were sensitive to the cumulative effects of climate change, land use, interspecific interactions, and scale, insights from the analysis might not emerge under a less complex model. Our integrated modeling framework provides valuable support for broader regional assessments, including estimation of risk to caribou and Indigenous food security, and for developing and evaluating potential caribou recovery strategies. © 2021 The Authors. The Journal of Wildlife Management published by Wiley Periodicals LLC on behalf of The Wildlife Society.