Program review. The Interdisciplinary Biophysics Graduate Program at the University of Michigan

The Michigan Biophysics Graduate Program (MBGP) was established in 1949, making it one of the first such programs in the world. The intellectual base of the program was significantly broadened in the 1980 when faculty members from a number of other units on campus were invited to join. Currently over forty faculty members from a variety of disciplines participate as mentors for the Ph.D. students enrolled in the MBGP providing our students with rich opportunities for academic learning and research. The MBGP has two main objectives: 1) to provide graduate students with both the intellectual and technical training in modern biophysics, 2) to sensitize our students to the power and unique opportunities of interdisciplinary work and thinking so as to train them to conduct research that crosses the boundaries between the biological and physical sciences. The program offers students opportunities to conduct research in a variety of areas of contemporary biophysics including structural biology, single molecule spectroscopy, spectroscopy and its applications, computational biology, membrane biophysics, neurobiophysics and enzymology. The MBGP offers a balanced curriculum that aims to provide our students with a strong academic base and, at the same time, accommodate their different academic backgrounds. Judging its past performance through the success of its former students, the MBGP has been highly successful, and there is every reason to believe that strong training in the biophysical sciences, as provided by the MBGP, will become even more valuable in the future both in the academic and the industrial settings. in the academic and the industrial settings.     

Campylobacter spp., Giardia spp., Cryptosporidium spp., Noroviruses, and Indicator Organisms in Surface Water in Southwestern Finland, 2000-2001

A total of 139 surface water samples from seven lakes and 15 rivers in southwestern Finland were analyzed during five consecutive seasons from autumn 2000 to autumn 2001 for the presence of various enteropathogens (Campylobacter spp., Giardia spp., Cryptosporidium spp., and noroviruses) and fecal indicators (thermotolerant coliforms, Escherichia coli, Clostridium perfringens, and F-RNA bacteriophages) and for physicochemical parameters (turbidity and temperature); this was the first such systematic study. Altogether, 41.0% (57 of 139) of the samples were positive for at least one of the pathogens; 17.3% were positive for Campylobacter spp. (45.8% of the positive samples contained Campylobacter jejuni, 25.0% contained Campylobacter lari, 4.2% contained Campylobacter coli, and 25.0% contained Campylobacter isolates that were not identified), 13.7% were positive for Giardia spp., 10.1% were positive for Cryptosporidium spp., and 9.4% were positive for noroviruses (23.0% of the positive samples contained genogroup I and 77.0% contained genogroup II). The samples were positive for enteropathogens significantly (P < 0.05) less frequently during the winter season than during the other sampling seasons. No significant differences in the prevalence of enteropathogens were found when rivers and lakes were compared. The presence of thermotolerant coliforms, E. coli, and C. perfringens had significant bivariate nonparametric Spearman's rank order correlation coefficients (P < 0.001) with samples that were positive for one or more of the pathogens analyzed. The absence of these indicators in a logistic regression model was found to have significant predictive value (odds ratios, 1.15 × 10⁸, 7.57, and 2.74, respectively; P < 0.05) for a sample that was negative for the pathogens analyzed. There were no significant correlations between counts or count levels for thermotolerant coliforms or E. coli or the presence of F-RNA phages and pathogens in the samples analyzed.     

Epithelial-specific histone modification of the <Emphasis Type="Italic">miR-96/182</Emphasis> locus targeting <Emphasis Type="Italic">AMAP1</Emphasis> mRNA predisposes p53 to suppress cell invasion in epithelial cells

Background

TP53 mutations in cancer cells often evoke cell invasiveness, whereas fibroblasts show invasiveness in the presence of intact TP53. AMAP1 (also called DDEF1 or ASAP1) is a downstream effector of ARF6 and is essential for the ARF6-driven cell-invasive phenotype. We found that AMAP1 levels are under the control of p53 (TP53 gene product) in epithelial cells but not in fibroblasts, and here addressed that molecular basis of the epithelial-specific function of p53 in suppressing invasiveness via targeting AMAP1.

Methods

Using MDA-MB-231 cells expressing wild-type and p53 mutants, we identified miRNAs in which their expression is controlled by normal-p53. Among them, we identified miRNAs that target AMAP1 mRNA, and analyzed their expression levels and epigenetic statuses in epithelial cells and nonepithelial cells.

Results

We found that normal-p53 suppresses AMAP1 mRNA in cancer cells and normal epithelial cells, and that more than 30 miRNAs are induced by normal-p53. Among them, miR-96 and miR-182 were found to target the 3′-untranslated region of AMAP1 mRNA. Fibroblasts did not express these miRNAs at detectable levels. The ENCODE dataset demonstrated that the promoter region of the miR-183-96-182 cistron is enriched with H3K27 acetylation in epithelial cells, whereas this locus is enriched with H3K27 trimethylation in fibroblasts and other non-epithelial cells. miRNAs, such as miR-423, which are under the control of p53 but not associated with AMAP1 mRNA, demonstrated similar histone modifications at their gene loci in epithelial cells and fibroblasts, and were expressed in these cells.

Conclusion

Histone modifications of certain miRNA loci, such as the miR-183-96-182 cistron, are different between epithelial cells and non-epithelial cells. Such epithelial-specific miRNA regulation appears to provide the molecular basis for the epithelial-specific function of p53 in suppressing ARF6-driven invasiveness.

     

Characterizing the growth of <Emphasis Type="Italic">Sarcoptes scabiei</Emphasis> infrapopulations

The plant stress hypothesis posits that a herbivore’s reproductive success increases when it feeds on stressed plants, while the plant vigor hypothesis predicts that a herbivore preferentially feeds on more vigorous plants. We examined these opposing hypotheses by growing spider mites (Tetranychus urticae) on the leaves of stressed and healthy (vigorous) cucumber plants. Host plants were grown under controlled conditions at low, moderate, and high concentrations of NaCl (to induce salinity stress), at low, moderate, and high fertilizer concentrations (to support growth), and without these additions (control). The effects of these treatments were evaluated by measuring fresh and dry plant biomass, carotenoid and chlorophyll content, antioxidant enzyme activity, and concentrations of PO₄^3?, K⁺, and Na⁺ in plant tissues. The addition of low concentrations of fertilizer increased dry mass, protein, and carotenoid content relative to controls, suggesting a beneficial effect on plants. The highest NaCl treatment (2560 mg L^?1) resulted in increased Na⁺ and protein content relative to control plants, as well as reduced PO₄^3?, K⁺, and chlorophyll levels and reduced catalase and ascorbate peroxidase enzyme activity levels. Analysis of life table data of T. urticae mites raised on leaves from the aforementioned plant groups showed the intrinsic rate of increase (r) for mites was 0.167 day^?1 in control specimens, 0.125 day^?1 for mites reared on plants treated with a moderate concentration of fertilizer (10 mL L^?1), and was highest (0.241 day^?1) on plants grown under moderate salinity conditions (1920 mg L^?1 NaCl). Reproductive success of T. urticae did not differ on plants watered with a moderate concentration of NaCl or a high concentration of fertilizer. The moderately-stressed plants formed a favorable environment for the development and reproduction of spider mites, supporting the plant stress hypothesis.     

Physiological and autonomic stress responses after prolonged sleep restriction and subsequent recovery sleep in healthy young men

Sleep and Biological Rhythms - Sleep restriction is increasingly common and associated with the development of health problems. We investigated how the neuroendocrine stress systems respond to...