Effect of magnesium on the growth and cell cycle of transformed and non-transformed epithelial rat liver cells in vitro

The effects of magnesium (Mg) restriction on cell growth and the cell cycle were determined in transformed (TRL-8) and non-transformed (TRL-12-15) epithelial-like rat liver cells. Cells were cultured in RPMI 1640 medium in which the Mg concentration was reduced to 0.5, 0.1, and 0 × the concentration in the regular RPMI 1640 media (100mg/l). Cell growth in the transformed cells was not influenced by the Mg restriction as greatly as in the non-transformed cell line. Transit through the cell cycle also exhibited an independence of the Mg in the medium in the transformed cells. When transformed cells were grown for two generations in Mg-limited medium, the growth rate slowed to a rate similar to that demonstrated by the non-transformed cells. Analysis by flow cytometry showed that transit through the cell cycle was minimally slowed in Mg deficient transformed cells; however, transit through the G₁ and S phases in the non-transformed cells was slowed. The TRL-8 cells in Mg-limited medium resulted in fewer nuclei in G₁ with subsequent increases in the percentages of S-phase nuclei. The TRL 12-15 cells reacted oppositely with the number of G₁ nuclei increased and the number of S-phase nuclei decreased. In respect to growth, these results show that epithelial cells respond in a similar manner to Mg-limitation as do fibroblast cells. The transformed cells exhibited a level of independence from Mg in respect to growth, reproduction, and cell-cycle kinetics.     

EGL-9 Controls C. elegans Host Defense Specificity through Prolyl Hydroxylation-Dependent and -Independent HIF-1 Pathways

Understanding host defense against microbes is key to developing new and more effective therapies for infection and inflammatory disease. However, how animals integrate multiple environmental signals and discriminate between different pathogens to mount specific and tailored responses remains poorly understood. Using the genetically tractable model host Caenorhabditis elegans and pathogenic bacterium Staphylococcus aureus, we describe an important role for hypoxia-inducible factor (HIF) in defining the specificity of the host response in the intestine. We demonstrate that loss of egl-9, a negative regulator of HIF, confers HIF-dependent enhanced susceptibility to S. aureus while increasing resistance to Pseudomonas aeruginosa. In our attempt to understand how HIF could have these apparently dichotomous roles in host defense, we find that distinct pathways separately regulate two opposing functions of HIF: the canonical pathway is important for blocking expression of a set of HIF-induced defense genes, whereas a less well understood noncanonical pathway appears to be important for allowing the expression of another distinct set of HIF-repressed defense genes. Thus, HIF can function either as a gene-specific inducer or repressor of host defense, providing a molecular mechanism by which HIF can have apparently opposing roles in defense and inflammation. Together, our observations show that HIF can set the balance between alternative pathogen-specific host responses, potentially acting as an evolutionarily conserved specificity switch in the host innate immune response.     

Primary Care Detection of Chronic Kidney Disease in Adults with Type-2 Diabetes: The ADD-CKD Study (Awareness,Detection and Drug Therapy in Type 2 Diabetes and Chronic Kidney Disease)

This US, multicenter, observational study assessed the CKD prevalence in adult patients with type-2 diabetes mellitus (T2DM) and characterized the proportion of detected and undiagnosed CKD in the primary care setting using the following: a clinician survey; a patient physical exam and medical history; a single blood draw for estimated glomerular filtration rate (eGFR) and glycosolated hemoglobin (HbA1c); urine dipstick for protein; urine albumin-creatinine ratio (ACR); two patient quality of life questionnaires; and a 15-month medical record review. The study consisted of 9339 adults with T2DM and 466 investigator sites. Of the 9339 enrolled, 9307 had complete data collection for analysis. The 15-month retrospective review showed urine protein, urine ACR, and eGFR testing were not performed in 51.4%, 52.9% and 15.2% of individuals, respectively. Of the 9307 patients, 5036 (54.1%) had Stage 1–5 CKD based on eGFR and albuminuria; however, only 607 (12.1%) of those patients were identified as having CKD by their clinicians. Clinicians were more successful in diagnosing patients with Stage 3–5 CKD than Stages 1 and 2. There were no differences in clinicians’ likelihood of identification of CKD based on practice setting, number of years in practice, or self-reported patients seen per week. Awareness or patient self-reported CKD was 81.1% with practitioner detection versus 2.6% in the absence of diagnosis. Primary care of T2DM demonstrates recommended urine CKD testing is underutilized, and CKD is significantly under-diagnosed. This is the first study to show CKD detection is associated with awareness.     

β-aminoisobutyric Acid,l-BAIBA,Is a Muscle-Derived Osteocyte Survival Factor

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Effects of emergence date and maternal size on egg development and sizes of eggs and first-instar nymphs of a semelparous aquatic insect

We examined whether or not sizes of eggs and offspring were related to emergence date or maternal size in a semelparous aquatic insect (the burrowing mayfly, Hexagenia) in which parental care is lacking and oviposited eggs are passively dispersed. We quantified the size of males and female imagos over the emergence span at a site on the Detroit River, Canada, and investigated relationships between emergence date and female size and (1) egg size and (2) size of first-instar nymphs. Although size of female imagos (H. limbata and H. rigida combined) declined significantly (P<0.025) over the emergence season, there was no significant relationship between body length and emergence date for males of either species. Males were significantly (P<0.001) smaller than females. H. limbata eggs, subsampled from three individuals from each of three size classes of female imagos collected on seven sampling dates, were measured using video image analysis. Eggs (n=100) oviposited by each of 63 H. limbata imagos were inspected daily for hatching. Newly hatched nymphs were removed, counted and measured. Egg size (P<0.001) and size of first-instar nymphs (P<0.001) varied significantly with emergence date, but not maternal size. The largest eggs and newly hatched nymphs occurred at peak emergence of adults. The synchronous release of larger (faster-sinking) eggs may result in reduced predation. Plasticity in egg development time and egg and nymph size may account for the ability of this taxon to recover from episodes of massive population reduction. Received: 12 March 1996 / Accepted: 24 February 1997