Microbial transformation of sterols

Summary Arthrobacter simplex, Serratia marcescens, Fusarium and Mycobacterium were tested for their ability to transform phytosterol to Androsta 1, 4 diene 3, 17 dione (ADD). Arthrobacter simplex ATCC 6946 was found to be more efficient than the other species tested.     

Role of adrenals on the 24-hour periodicity in hypothalamo-pituitary axis in male rat

Studies were carried out to investigate the influence of adrenalectomy on the 24 hour periodicity in the hypothalamo-pituitary axis in adult male rat. Adrenal gland ablation resulted in the shift in the occurrence of peak content of hypothalamic LHRH and attenuation in the responsiveness of the pituitary to synthetic LHRH. Following adrenalectomy, the circadian serum LH peak was attenuated and serum FSH showed a 24 hour periodicity. In conclusion, the results suggest the possible role of adrenal gland in the maintenance of 24 hour periodicity of hormones in the hypothalamo-hypophyseal axis in male rat.     

Study of the atherogenic dyslipoproteinemia induced by dietary cholesterol in rhesus monekys (Macaca mulatta).

Hypercholesterolemia was induced in adult male rhesus monkeys with a high-fat diet containing an elevated cholesterol level (0.5%). Plasma lipoproteins were chromatographically separated into four size populations (regions) that were subdivided by density until fractions with single electrophoretic mobilities were obtained. The region III lipoproteins (LDL) contained 80% of plasma cholesterol and were present in the highest concentration of all fractions. Their molecular weight was increased over that of controls so that each particle averaged 1.8 times the number of cholesteryl ester molecules as did control LDL. Region II lipoproteins, a heterogeneous group, were present in next highest concentration. Most were cholesteryl ester-rich, beta-migrating lipoproteins that overlapped the VLDL and LDL density ranges; apoB was the predominant apoprotein. One region II subfraction had pre beta 2 migration and the density range. 1.050 less than d less than 1.10. Another subfraction, cholesteryl ester-rich VLDL including only about 1% of plasma cholesterol, had pre beta 1 migration and apoB and apoC as the predominant apoproteins with no apoprotein E. Region I lipoproteins were larger sized, slow beta-migrating cholesteryl ester-rich VLDL that included 5% of plasma cholesterol. ApoB and apoE were the predominant apoproteins. Region IV lipoproteins (HDL) contained 4% of the plasma cholesterol; their concentration was decreased to about 1/3 of the control level. Atherogenic features of the diet-induced dyslipoproteinemia included the increased plasma concentrations and cholesteryl ester contents of the region I, II, and III lipoproteins in addition to the decreased HDL concentration.     

Identification of the primate papovavirus HD as the stump-tailed macaque virus.

The recently isolated primate papovavirus HD is shown to be indistinguishable from the stump-tailed macaque virus by immunofluorescent reactivity, by restriction endonuclease analysis, and by nucleic acid hybridization assay.     

Studies on transducing phage M-1 for Rhizobium japonicum D211

Phage M-1 produced clear plaques with a halo in the lawn of Rhizobium japonicum D211. A one step growth curve of phage M-1 showed a latent period of 3 h, burst size of 55 and rise period of 2 h. The inactivation of phage M-1 was found to be dependent upon the concentraion of d-glucosomanine. The neutralization kinetics of phage M-1 by antiphage serum gave a K value (velocity constant) of 83.1 min^–1. Transduction of str and kan was studied in the presence of antiphage serum and d-glucosamine. Cotransduction of different antibiotic resistance markers suggested that the system can be further explored for high resolution mapping in R. japonicum.Abbreviations YM yeast mannitol medium - PFU plaque forming unit - moi multiplicity of infection - EOP efficiency of plating     

Complex mitochondrial DNA in Drosophila.

The larval mtDNA isolated from D. virilis, D. simulans and D. melanogaster exists in complex molecular forms in addition to the simple monomeric circular form. The frequency of circular dimers and oligomers is highly elevated in apparently normal larval tissues. These complex forms of mtDNA are separable on agarose gels. Hind III restriction endonuclease and electron microscopic analyses used in the present study have revealed that circular dimers are simply the circular concatemers of two monomeric circles which are arranged in a head-to-tail structure with no detectable heterologous regions such as insertions or deletions. The electrophoretic patterns of Hind III digested mtDNAs of D. simulans and D. melanogaster (sibling species) are identical and distinguishable from that of distantly related species, D. virilis.     

Genetic variants of cytoplasmic malate dehydrogenase (MDH:EC:1.1.1.37) in populations in England and the Indian subcontinent

Summary A new variant malate dehydrogenase is described, designated S-MDH^Ind to indicate its discovery in the Indian subcontinent pending full comparison with all other variants. It occurred during a survey of the incidence of variant S-MDH phenotypes in 4149 subjects in north-east England and 1494 subjects from several populations in the Indian region. The variants previously thought to be restricted to the New Guinea region and to African populations occurred in three English subjects in northeast England. The incidence of variant S-MDH phenotypes in other populations is summarised.     

THE EFFECTS OF RED BLOOD CELL EXTRACTS ON THE PROLIFERATION OF ERYTHROCYTE PRECURSOR CELLS, IN VIVO

Saline incubation extracts of mature erythrocytes were assayed in vivo by a variety of techniques in order to study their ability to modify the proliferation of maturing erythroid cells. Using comparable extracts from granulocytes and lymphocytes, the specificity of the effect of the red cell extract for erythroid cells was confirmed by measurement of autoradiographic labelling indices, radio-iron incorporation and spleen colony growth. The erythroid cells were found to be very sensitive to the effects of the extract, as little as 10 μg per mouse producing a maximum effect on iron incorporation. It was found that the extract does not block erythroid cell proliferation completely but simply lengthens the cell cycle, mainly by increasing the G₁ phase of the cycle. There was no effect on the committed erythroid precursor cells. The in vivo activity, specificity and non-toxicity to the cells, together with the cells' sensitivity to red cell extract suggest, therefore, that this inhibitor may play a physiological role in the control of red cell production.     

Division of labor within the DNA damage tolerance system reveals non-epistatic and clinically actionable targets for precision cancer medicine

Crosslink repair depends on the Fanconi anemia pathway and translesion synthesis polymerases that replicate over unhooked crosslinks. Translesion synthesis is regulated via ubiquitination of PCNA, and independently via translesion synthesis polymerase REV1. The division of labor between PCNA-ubiquitination and REV1 in interstrand crosslink repair is unclear. Inhibition of either of these pathways has been proposed as a strategy to increase cytotoxicity of platinating agents in cancer treatment. Here, we defined the importance of PCNA-ubiquitination and REV1 for DNA in mammalian ICL repair. In mice, loss of PCNA-ubiquitination, but not REV1, resulted in germ cell defects and hypersensitivity to cisplatin. Loss of PCNA-ubiquitination, but not REV1 sensitized mammalian cancer cell lines to cisplatin. We identify polymerase Kappa as essential in tolerating DNA damage-induced lesions, in particular cisplatin lesions. Polk-deficient tumors were controlled by cisplatin treatment and it significantly delayed tumor outgrowth and increased overall survival of tumor bearing mice. Our results indicate that PCNA-ubiquitination and REV1 play distinct roles in DNA damage tolerance. Moreover, our results highlight POLK as a critical TLS polymerase in tolerating multiple genotoxic lesions, including cisplatin lesions. The relative frequent loss of Polk in cancers indicates an exploitable vulnerability for precision cancer medicine.     

Comparing Accuracy of Wrist Intra-articular Needle Placement Via Ulnocarpal Approach by Training Level: A Cadaveric Study

BackgroundIntra-articular injections are a standard therapy and diagnostic tool for a variety of wrist conditions. Accurate needle placement is crucial for proper therapeutic benefit and prevention of complications. While some studies claim accurate needle placement requires imaging, others conclude that anatomical guidance is sufficient. This study aimed to evaluate the accuracy of intra-articular wrist needle placement with the ulnocarpal approach across differing levels of training using clinical anatomy alone.MethodsFourteen fresh-frozen, above-elbow cadaveric specimens were used. Intra-articular needle placement into the wrist via an ulnocarpal approach was attempted by nine study participants: two interns, two junior-level residents, two senior-level residents, two hand fellows, and one attending hand surgeon. Each injection was performed based on clinical examination and landmarks alone. The number of attempts and total time taken for each injection was recorded.ResultsOverall success rate was 71%, (89 of 126 attempts) and did not vary significantly across levels of training. Average time for needle placement among all participants was 10.9 ± 6.5 seconds. Timing of successful intra-articular needle placement (10.4 ± 5.2 seconds) significantly differed between levels. However, timing did not trend in any direction with more or less training. No significant difference was noted in total attempts or attempts with successful outcomes when comparing level of training.ConclusionThe ulnocarpal approach is a viable option for injection or aspiration of the wrist without image guidance. We were unable to show any relevant trends with timing or number of attempts in comparison to level of training. Level of Evidence: V