The New State Preemption, The Future of Home Rule, and The Illinois Experience

This article examines the rise of new forms of state preemption of local government legal authority in states across the nation, a trend that is prompting scholars, advocates, and officials to re-examine the underlying nature of home rule. The article lays out core components of a new approach to home rule that might remedy contemporary shortcomings in the doctrine, then reflects on lessons for reforming home rule from the Illinois experience

The Interrupted Task Paradigm: Age and Observer-Performer Differences

Previous research has indicated a developmental tendency toward greater repetition choice and recall of interrupted tasks than for completed tasks. The present study investigated this relationship and the possibility that observing versus performing a task might have differential effects on recall and repetition choice. Thirteen ten year old and eleven year old boys (performers) individually assembled eighteen jig-saw puzzles of birds and animals. Twenty-four peers of the same age (observers) observers puzzle assembly. Contrary to previous research, no significant tendency was found for older participants to recall and to choose to repeat more interrupted tasks than for younger participants. However, observers revelaed a significantly greater tendency than performers to chose to repeat interrupted tasks. No comparable difference was apparent for recall scores. These results are discussed in the context of numerous problems apparent in previous research. Implications for future research using the interrupted task paradigm are also considered

Pharmacologic therapy for vitamin D deficiency

Cholecalciferol (vitamin D3) supplementation should be used for vitamin D repletion because it may be more effective in preventing nonvertebral fractures. (Strength of Recommendation [SOR]: B, based on subgroup analysis of randomized controlled trials [RCTs].) Cholecalciferol produces higher serum 25-hydroxyvitamin D levels than ergocalciferol (vitamin D2). Vitamin D therapy may be given daily or weekly with equal effectiveness; the dosage depends on the degree of deficiency. (SOR: C, based on an RCT and cohort study.) The cumulative dosage is more important than dosing frequency, so the choice of daily, weekly, or monthly dosing can be based on patient preference. (SOR: C, based on an RCT.) Vitamin D levels should be rechecked after three months to ensure adequate response. (SOR: C, based on an observational study.

Smelt Was the Likely Beneficiary of an Antifreeze Gene Laterally Transferred Between Fishes

Background Type II antifreeze protein (AFP) from the rainbow smelt, Osmerus mordax, is a calcium-dependent C-type lectin homolog, similar to the AFPs from herring and sea raven. While C-type lectins are ubiquitous, type II AFPs are only found in a few species in three widely separated branches of teleost fishes. Furthermore, several other non-homologous AFPs are found in intervening species. We have previously postulated that this sporadic distribution has resulted from lateral gene transfer. The alternative hypothesis, that the AFP evolved from a lectin present in a shared ancestor and that this gene was lost in most species, is not favored because both the exon and intron sequences are highly conserved. Results Here we have sequenced and annotated a 160 kb smelt BAC clone containing a centrally-located AFP gene along with 14 other genes. Quantitative PCR indicates that there is but a single copy of this gene within the smelt genome, which is atypical for fish AFP genes. The corresponding syntenic region has been identified and searched in a number of other species and found to be devoid of lectin or AFP sequences. Unlike the introns of the AFP gene, the intronic sequences of the flanking genes are not conserved between species. As well, the rate and pattern of mutation in the AFP gene are radically different from those seen in other smelt and herring genes. Conclusions These results provide stand-alone support for an example of lateral gene transfer between vertebrate species. They should further inform the debate about genetically modified organisms by showing that gene transfer between ‘higher’ eukaryotes can occur naturally. Analysis of the syntenic regions from several fishes strongly suggests that the smelt acquired the AFP gene from the herring

Ku70 Is Required for Late B Cell Development and Immunoglobulin Heavy Chain Class Switching

Immunoglobulin (Ig) heavy chain (HC) class switch recombination (CSR) is a late B cell process that involves intrachromosomal DNA rearrangement. Ku70 and Ku80 form a DNA end-binding complex required for DNA double strand break repair and V(D)J recombination. Ku70^(−/−) (K70T) mice, like recombination activating gene (RAG)-1– or RAG-2–deficient (R1T or R2T) mice, have impaired B and T cell development at an early progenitor stage, which is thought to result at least in part from defective V(D)J recombination (Gu, Y., K.J. Seidl, G.A. Rathbun, C. Zhu, J.P. Manis, N. van der Stoep, L. Davidson, H.L. Cheng, J.M. Sekiguchi, K. Frank, et al. 1997. Immunity. 7:653–665; Ouyang, H., A. Nussenzweig, A. Kurimasa, V.C. Soares, X. Li, C. Cordon-Cardo, W. Li, N. Cheong, M. Nussenzweig, G. Iliakis, et al. 1997. J. Exp. Med. 186:921–929). Therefore, to examine the potential role of Ku70 in CSR, we generated K70T mice that carry a germline Ig HC locus in which the JH region was replaced with a functionally rearranged VH(D)JH and Ig λ light chain transgene (referred to as K70T/HL mice). Previously, we have shown that B cells from R1T or R2T mice carrying these rearranged Ig genes (R1T/HL or R2T/HL mice) can undergo CSR to IgG isotypes (Lansford, R., J. Manis, E. Sonoda, K. Rajewsky, and F. Alt. 1998. Int. Immunol. 10:325–332). K70T/HL mice had significant numbers of peripheral surface IgM^+ B cells, which generated serum IgM levels similar to those of R2T/HL mice. However, in contrast to R2T/HL mice, K70T/HL mice had no detectable serum IgG isotypes. In vitro culture of K70T/HL B cells with agents that induce CSR in normal or R2T/HL B cells did lead to the induction of germline CH transcripts, indicating that initial signaling pathways for CSR were intact in K70T/HL cells. However, treatment with such agents did not lead to detectable CSR by K70T/HL B cells, and instead, led to cell death within 72 h. We conclude that Ku70 is required for the generation of B cells that have undergone Ig HC class switching. Potential roles for Ku70 in the CSR process are discusse

Mechanistic insights into the role of microRNAs in cancer: influence of nutrient crosstalk

A plethora of studies have described the disruption of key cellular regulatory mechanisms involving non-coding RNAs, specifically microRNAs (miRNA) from the let-7 family, the miR-17 family, miR-21, miR-143, and the miR-200 family, which contribute to aberrant signaling and tumor formation. Certain environmental factors, such as bioactive dietary agents, e.g., folate, curcumin, polyunsaturated fatty acids, are also thought to impact the progression and severity of cancer. In terms of the chemoprotective mechanisms of action, these bioactive dietary agents appear to act, in part, by modulating tissue levels of miR-16, miR-17 family, miR-26b, miR-106b, and miR-200 family miRNAs and their target genes. However, the mechanisms of nutrient action are not yet fully understood. Therefore, additional characterization of the putative underlying mechanisms is needed to further our understanding of the biology, early diagnosis, prevention, and the treatment of cancer. For the purpose of elucidating the epigenetic landscape of cancer, this review will summarize the key findings from recent studies detailing the effect of bioactive dietary agents on miRNA regulation in cancer

Interleukin-2 receptor α chain regulates the size and content of the peripheral lymphoid compartment

AbstractInterleukin-2 receptor α chain (IL-2Rα) expression occurs at specific stages of early T and B lymphocyte development and is induced upon activation of mature lymphocytes. Young mice that lack IL-2Rα have phenotypically normal development of T and B cells. However, as adults, these mice develop massive enlargement of peripheral lymphoid organs associated with polyclonal T and B cell expansion, which, for T cells, is correlated with impaired activation-induced cell death in vivo. Older IL-2Rα-deficient mice also develop autoimmune disorders, including hemolytic anemia and inflammatory bowel disease. Thus, IL-2Rα is essential for regulation of both the size and content of the peripheral lymphoid compartment, probably by influencing the balance between clonal expansion and cell death following lymphocyte activation

Evaluation of fecal mRNA reproducibility via a marginal transformed mixture modeling approach

<p>Abstract</p> <p>Background</p> <p>Developing and evaluating new technology that enables researchers to recover gene-expression levels of colonic cells from fecal samples could be key to a non-invasive screening tool for early detection of colon cancer. The current study, to the best of our knowledge, is the first to investigate and report the reproducibility of fecal microarray data. Using the intraclass correlation coefficient (ICC) as a measure of reproducibility and the preliminary analysis of fecal and mucosal data, we assessed the reliability of mixture density estimation and the reproducibility of fecal microarray data. Using Monte Carlo-based methods, we explored whether ICC values should be modeled as a beta-mixture or transformed first and fitted with a normal-mixture. We used outcomes from bootstrapped goodness-of-fit tests to determine which approach is less sensitive toward potential violation of distributional assumptions.</p> <p>Results</p> <p>The graphical examination of both the distributions of ICC and probit-transformed ICC (PT-ICC) clearly shows that there are two components in the distributions. For ICC measurements, which are between 0 and 1, the practice in literature has been to assume that the data points are from a beta-mixture distribution. Nevertheless, in our study we show that the use of a normal-mixture modeling approach on PT-ICC could provide superior performance.</p> <p>Conclusions</p> <p>When modeling ICC values of gene expression levels, using mixture of normals in the probit-transformed (PT) scale is less sensitive toward model mis-specification than using mixture of betas. We show that a biased conclusion could be made if we follow the traditional approach and model the two sets of ICC values using the mixture of betas directly. The problematic estimation arises from the sensitivity of beta-mixtures toward model mis-specification, particularly when there are observations in the neighborhood of the the boundary points, 0 or 1. Since beta-mixture modeling is commonly used in approximating the distribution of measurements between 0 and 1, our findings have important implications beyond the findings of the current study. By using the normal-mixture approach on PT-ICC, we observed the quality of reproducible genes in fecal array data to be comparable to those in mucosal arrays.</p