Effect of specific dietary fatty acids on lipogenesis in the livers and mammary glands of lactating mice

The effects of linoleic, linolenic and columbinic acids fed as 4% of a high carbohydrate (50% glucose) diet on the activities and the amounts of several enzymes associated with fatty acid synthesis in livers and mammary glands of lactating mice were compared with those for stearic and oleic acids. Fatty acid synthesis, measured in vivo, was significantly lower in livers of mice ingesting all 3 polyunsaturated fatty acids (PUFA), whereas in mammary glands synthesis was lower only in mice receiving columbinic acid. The activities of fatty acid synthetase (FAS) and acetyl CoA carboxylase were significantly reduced in liver by all 3 PUFA, as were activities of glucose-6-phosphate dehydrogenase, malic enzyme (ME) and citrate cleavage enzyme (CCE), also associated with lipogenesis. In mammary gland, on the other hand, the activities of these enzymes were unaffected by dietary PUFA. The tissue contents of FAS, ME and CCE, measured by rocket immunoelectrophoresis, were found to be significantly reduced in liver by linoleate, linolenate and columbinate but were not significantly altered in mammary gland. The decrease in hepatic lipogenesis observed was principally due to a decrease in the amounts of these enzymes induced by the dietary PUFA but the inhibition in mammary gland caused by columbinate could not be accounted for by a reduction in enzyme contents and therefore may be due to allosteric effects which occur when fatty acid synthesis is measured with³H₂O. The fatty acid composition in liver and mammary gland of dams and in liver and kidney of pups completely reflected dietary fatty acids. Columbinate made up ca. 20% of the total fatty acids in both tissues of the columbinic acid-fed mice and ca. 15% in the pup tissues. This suggests that columbinate is incorporated into milk lipids of dams and is easily absorbed by pups. The elevated ratios of 16/16∶1 and 18/18∶1 in liver and mammary gland of dams and liver and kidney of the pups from dams fed linoleate, linolenate and columbinate suggest that each of these polyunsaturated fatty acids in the diet can inhibit the activity of Δ9 desaturase.     

Archival Appraisal and the Digital Record: Applying Past Tradition for Future Practice

The digital revolution has changed the daily work of archivists. As a result, archivists have refined their analog practices and initiated new ones to accommodate the unique information creation and access needs of users. While limitless storage and technological obsolescence may be surmountable challenges, appraisal continues to be a necessary component of this preservation enterprise. Macro-appraisal—a top-down functional assessment of an organization’s high-level decision making that defines the enduring value of specific bodies of documentary evidence of these creative or administrative processes—is used to facilitate the management of diverse bodies of born-digital records in archives and special collections.     

Primary focal segmental glomerulosclerosis: clinical course and response to therapy

Primary focal segmental glomerulosclerosis (FSGS) is a lesion associated with a poor prognosis and results in end-stage renal disease after 5 to 10 years. Based on past experience, many nephrologists have considered primary FSGS a lesion that is steroid resistant and therefore are reluctant to offer steroids as treatment. Recent data, however, have demonstrated that patients with primary FSGS have a response to steroid therapy that is considerably better than had been described. Thus, it may be that nephrologists have been more "steroid reluctant" than the lesion is steroid resistant. To better understand this issue we review the clinical course and response to therapy in patients with primary FSGS.     

Longitudinal analysis of utilization of inpatient treatment based on insurance data of mandatory health insurance

AIM: To investigate which of the routinely collected claims data from the German "Legal sickness funds" on hospital utilisation may be used, in addition to that prescribed by the legislator. DESIGN: We used claims data to study a cohort of sickness fund beneficiaries who were insured during the complete year 1992 (n = 81,309). Six utilisation parameters, using the number of cases and in hospital days overall as well as diseases specific (i.e. readmission rates, in-hospital days per person with [at least] one hospital stay) were calculated. RESULTS: There are 88 persons with (at least) one hospital stay, 116 hospital cases and a total of 1306 in-hospital days per 1000 insured persons in the study cohort. The average hospital days per person (14.8 days) are ca. 30% higher than the average length of stay (11.2 days). Hospital utilisation increases with age. Hospital stays associated with ICD-239 (neoplasms of unknown origin) resulted in a higher than average number of hospital days in total although the mean length of stay is not above the average. This is due to a high readmission rate. Hospital stays associated with elective surgical procedures have a high prevalence rate but a low readmission ratio and short length of stay. CONCLUSION: The parameters related to insured persons, cases and specifically personal parameters of hospital utilisation allow a detailed analysis of hospital care; different utilisation and user patterns can be investigated and possible determinants of utilisation can be identified. After technical transformation, routine data of the sickness funds can be used to obtain information relevant for health care planners as well as for quality management.     

Verapamil-induced "primary" polydipsia

An 11-month-old male infant with recurrent supraventricular tachycardia (SVT) was treated with oral verapamil. Shortly thereafter he developed marked changes in behavior including lethargy, intensely increased thirst and urination, and irritability when denied fluids. "Primary" polydipsia was diagnosed following an evaluation which showed no evidence of adrenal insufficiency, diabetes insipidus, diabetes mellitus, hypercalcemia, hyperosmolality, or renal disease. The symptoms resolved 1 week after verapamil was discontinued.     

Self-organizing maps for pattern recognition in design of alloys

A combined experimental–computational methodology for accelerated design of AlNiCo-type permanent magnetic alloys is presented with the objective of simultaneously extremizing several magnetic properties. Chemical concentrations of eight alloying elements were initially generated using a quasi-random number generator so as to achieve a uniform distribution in the design variable space. It was followed by manufacture and experimental evaluation of these alloys using an identical thermo-magnetic protocol. These experimental data were used to develop meta-models capable of directly relating the chemical composition with desired macroscopic properties of the alloys. These properties were simultaneously optimized to predict chemical compositions that result in improvement of properties. These data were further utilized to discover various correlations within the experimental dataset by using several concepts of artificial intelligence. In this work, an unsupervised neural network known as self-organizing maps was used to discover various patterns reported in the literature. These maps were also used to screen the composition of the next set of alloys to be manufactured and tested in the next iterative cycle. Several of these Pareto-optimized predictions out-performed the initial batch of alloys. This approach helps significantly reducing the time and the number of alloys needed in the alloy development process.     

Isolation, characterization, and partial purification of a novel ubiquitin-protein ligase, E3. Targeting of protein substrates via multiple and distinct recognition signals and conjugating enzymes

Degradation of a protein via the ubiquitin system involves two discrete steps, conjugation of ubiquitin to the substrate and degradation of the adduct. Conjugation follows a three-step mechanism. First, ubiquitin is activated by the ubiquitin-activating enzyme, E1. Following activation, one of several E2 enzymes (ubiquitin-carrier proteins or ubiquitin-conjugating enzymes, UBCs) transfers ubiquitin from E1 to the protein substrate that is bound to one of several ubiquitin-protein ligases, E3s. These enzymes catalyze the last step in the process, covalent attachment of ubiquitin to the protein substrate. The binding of the substrate to E3 is specific and implies that E3s play a major role in recognition and selection of proteins for conjugation and subsequent degradation. So far, only a few ligases have been identified, and it is clear that many more have not been discovered yet. Here, we describe a novel ligase that is involved in the conjugation and degradation of non "N-end rule" protein substrates such as actin, troponin T, and MyoD. This substrate specificity suggests that the enzyme may be involved in degradation of muscle proteins. The ligase acts in concert with E2-F1, a previously described non N-end rule UBC. Interestingly, it is also involved in targeting lysozyme, a bona fide N-end substrate that is recognized by E3 alpha and E2-14 kDa. The novel ligase recognizes lysozyme via a signal(s) that is distinct from the N-terminal residue of the protein. Thus, it appears that certain proteins can be targeted via multiple recognition motifs and distinct pairs of conjugating enzymes. We have purified the ligase approximately 200-fold and demonstrated that it is different from other known E3s, including E3 alpha/UBR1, E3 beta, and E6-AP. The native enzyme has an apparent molecular mass of approximately 550 kDa and appears to be a homodimer. Because of its unusual size, we designated this novel ligase E3L (large). E3L contains an -SH group that is essential for its activity. Like several recently described E3 enzymes, including E6-AP and the ligase involved in the processing of p105, the NF-kappa B precursor, the novel ligase is found in mammalian tissues but not in wheat germ.     

New Generations: Sequencing Machines and Their Computational Challenges

New generation sequencing systems are changing how molecular biology is practiced. The widely promoted ＄1000 genome will be a reality with attendant changes for healthcare, including personalized medicine. More broadly the genomes of many new organisms with large samplings from populations will be commonplace. What is less appreciated is the explosive demands on computation, both for CPU cycles and storage as well as the need for new computational methods. In this article we will survey some of these develo...