Tissue context determines the penetrance of regulatory DNA variation.

Functional assessment of disease-associated sequence variation at non-coding regulatory elements is complicated by their high degree of context sensitivity to both the local chromatin and nuclear environments. Allelic profiling of DNA accessibility across individuals has shown that only a select minority of sequence variation affects transcription factor (TF) occupancy, yet low sequence diversity in human populations means that no experimental assessment is available for the majority of disease-associated variants. Here we describe high-resolution in vivo maps of allelic DNA accessibility in liver, kidney, lung and B cells from 5 increasingly diverged strains of F1 hybrid mice.

Performativity Double Standards and the Sexual Orientation Climate at a Southern Liberal Arts University.

This study employs quantitative and qualitative methods to examine how heterosexual, bisexual, and gay students rate and describe a Southern, religiously affiliated university's sexual orientation climate. Using qualitative data, queer theory, and the concept tyranny of sexualized spaces, we explain why non-heterosexual students have more negative perceptions of the university climate than heterosexual male students, in both bivariate and multivariate analyses. Although heterosexual students see few problems with the campus sexual orientation climate, bisexual men and women describe being challenged on the authenticity of their orientation, and lesbian and, to a greater extent, gay male students report harassment and exclusion in a number of settings.

Patterns of local segregation: Do they matter for neighborhood crime?

In this paper, we extend recent research on the spatial measurement of segregation and the spatial dynamics of urban crime by conceptualizing, measuring, and describing local segregation by race-ethnicity and economic status, and examining the linkages of these conditions with levels of neighborhood violent and property crime. The analyses are based on all 8895 census tracts within a sample of 86 large U.S.

Mouse regulatory DNA landscapes reveal global principles of cis-regulatory evolution.

To study the evolutionary dynamics of regulatory DNA, we mapped >1.3 million deoxyribonuclease I-hypersensitive sites (DHSs) in 45 mouse cell and tissue types, and systematically compared these with human DHS maps from orthologous compartments. We found that the mouse and human genomes have undergone extensive cis-regulatory rewiring that combines branch-specific evolutionary innovation and loss with widespread repurposing of conserved DHSs to alternative cell fates, and that this process is mediated by turnover of transcription factor (TF) recognition elements.

Conservation of trans-acting circuitry during mammalian regulatory evolution.

The basic body plan and major physiological axes have been highly conserved during mammalian evolution, yet only a small fraction of the human genome sequence appears to be subject to evolutionary constraint. To quantify cis- versus trans-acting contributions to mammalian regulatory evolution, we performed genomic DNase I footprinting of the mouse genome across 25 cell and tissue types, collectively defining ∼8.6 million transcription factor (TF) occupancy sites at nucleotide resolution.

A comparative encyclopedia of DNA elements in the mouse genome.

The laboratory mouse shares the majority of its protein-coding genes with humans, making it the premier model organism in biomedical research, yet the two mammals differ in significant ways. To gain greater insights into both shared and species-specific transcriptional and cellular regulatory programs in the mouse, the Mouse ENCODE Consortium has mapped transcription, DNase I hypersensitivity, transcription factor binding, chromatin modifications and replication domains throughout the mouse genome in diverse cell and tissue types. By comparing with the human genome, we not only confirm substantial conservation in the newly annotated potential functional sequences, but also find a large degree of divergence of sequences involved in transcriptional regulation, chromatin state and higher order chromatin organization.

An expansive human regulatory lexicon encoded in transcription factor footprints.

Regulatory factor binding to genomic DNA protects the underlying sequence from cleavage by DNase I, leaving nucleotide-resolution footprints. Using genomic DNase I footprinting across 41 diverse cell and tissue types, we detected 45 million transcription factor occupancy events within regulatory regions, representing differential binding to 8.4 million distinct short sequence elements.

An encyclopedia of mouse DNA elements (Mouse ENCODE).

To complement the human Encyclopedia of DNA Elements (ENCODE) project and to enable a broad range of mouse genomics efforts, the Mouse ENCODE Consortium is applying the same experimental pipelines developed for human ENCODE to annotate the mouse genome.

The hypersensitive sites of the murine β-globin locus control region act independently to affect nuclear localization and transcriptional elongation.

The β-globin locus control region (LCR) is necessary for high-level β-globin gene transcription and differentiation-dependent relocation of the β-globin locus from the nuclear periphery to the central nucleoplasm and to foci of hyperphosphorylated Pol II "transcription factories" (TFys). To determine the contribution of individual LCR DNaseI hypersensitive sites (HSs) to transcription and nuclear location, in the present study, we compared β-globin gene activity and location in erythroid cells derived from mice with deletions of individual HSs, deletions of 2 HSs, and deletion of the whole LCR and found all of the HSs had a similar spectrum of activities, albeit to different degrees. Each HS acts as an independent module to activate expression in an additive manner, and this is correlated with relocation away from the nuclear periphery.

A functional element necessary for fetal hemoglobin silencing.

Background: An improved understanding of the regulation of the fetal hemoglobin genes holds promise for the development of targeted therapeutic approaches for fetal hemoglobin induction in the β-hemoglobinopathies. Although recent studies have uncovered trans-acting factors necessary for this regulation, limited insight has been gained into the cis-regulatory elements involved.

Methods: We identified three families with unusual patterns of hemoglobin expression, suggestive of deletions in the locus of the β-globin gene (β-globin locus).

Older couples' management of multiple-chronic illnesses: Individual and shared perceptions and coping in Type 2 diabetes and osteoarthritis.

Using data from interviews with 28 older couples in which 1 spouse was diagnosed with diabetes and osteoarthritis, we examined illness perceptions and coping activities as they relate to illness management and relationship resilience. Qualitative analysis of interview transcripts revealed categories of data related to perceptions, coping, and cross category comparisons. Findings suggest that couples experience both negative and positive perceptions of their illnesses, indicating a balance between the reality of their illness challenges and an optimistic outlook of the future.

Histone hyperacetylation within the beta-globin locus is context-dependent and precedes high-level gene expression.

Active gene promoters are associated with covalent histone modifications, such as hyperacetylation, which can modulate chromatin structure and stabilize binding of transcription factors that recognize these modifications. At the beta-globin locus and several other loci, however, histone hyperacetylation extends beyond the promoter, over tens of kilobases; we term such patterns of histone modifications "hyperacetylated domains." Little is known of either the mechanism by which these domains form or their function.

Maxillary obturator: a clinical case report.

The most frequent openings of the maxilla result from cleft palates or tumors that require either partial or total surgical removal of the palate. Intraoral defects in the maxilla can cause an opening into the nasopharynx complex. Cleft palates or surgically removed tumors can have a devastating effect on a patient's appearance and speech.

Rotational path removable partial denture: an esthetic alternative.

Missing teeth can be replaced using any of a number of methods. Patients may choose to replace missing teeth with a prosthesis that is either removable, fixed, or retained with implants. When it is necessary to replace anterior or posterior teeth, a properly designed and fabricated rotational path removable partial denture can be both successful and esthetically pleasing to the patient.

The locus control region is required for association of the murine beta-globin locus with engaged transcription factories during erythroid maturation.

We have examined the relationship between nuclear localization and transcriptional activity of the endogenous murine beta-globin locus during erythroid differentiation. Murine fetal liver cells were separated into distinct erythroid maturation stages by fluorescence-activated cell sorting, and the nuclear position of the locus was determined at each stage. We find that the beta-globin locus progressively moves away from the nuclear periphery with increasing maturation.

Flanking HS-62.5 and 3' HS1, and regions upstream of the LCR, are not required for beta-globin transcription.

The locus control region (LCR) was thought to be necessary and sufficient for establishing and maintaining an open beta-globin locus chromatin domain in the repressive environment of the developing erythrocyte. However, deletion of the LCR from the endogenous locus had no significant effect on chromatin structure and did not silence transcription. Thus, the cis-regulatory elements that confer the open domain remain unidentified.

PMMA: an essential material in medicine and dentistry.

The first use of polymethyl methacrylate (PMMA) as a dental device was for the fabrication of complete denture bases. Its qualities of biocompatibility, reliability, relative ease of manipulation, and low toxicity were soon seized upon and incorporated by many different medical specialties. PMMA has been used for (a) bone cements; (b) contact and intraocular lens; (c) screw fixation in bone; (d) filler for bone cavities and skull defects; and (e) vertebrae stabilization in osteoporotic patients.

Elder abuse update.

The following article offers an update on the topic of elder abuse. As the baby boomer generation ages, the number of elderly patients seeking all forms of dentistry will increase. This article is designed to inform dentists of their responsibility to the entire health of their patients.

Dental management of liver transplant patients.

Dentists are responsible for understanding treatment regimens concerning a myriad of health issues. Increasingly, patients who have significant liver disease or have undergone liver transplant therapy will seek either preoperative or postoperative care. This article reviews current protocols for managing these patients.

Redirection of central venous pressure catheters using a flow directed technique.

The malposition of the tip of a central venous catheter occurs in 5 to 30 per cent of the attempts. Repositioning of the catheter tip can be successfully and safely performed in 87.5 per cent of the patients using a Fogarty balloon catheter and flow directed techniques to float the CVP catheter to the ideal location in the superior vena cava.

Knotting and entanglement of multiple central venous catheters.

A 53-yr-old black male was admitted with peripheral vascular disease and septic shock. Appropriate cardiopulmonary resuscitation and operative intervention required the placement of multiple central venous lines. These included two subclavicular central venous pressure (CVP) catheters and one Swan-Ganz catheter (SGC).

Myeloblastoma (granulocytic sarcoma) of the ovary.

Myeloblastic neoplasms occur in patients with leukemia. In women, the ovary is a common site. The cells of the tumor are identical histochemically to those in the peripheral blood.

Randomized sequential hormonal therapy vs adrenalectomy for metastatic breast carcinoma.

One hundred sixty-one postmenopausal and 65 premenopausal women, a total of 226 patients with metastatic breast carcinoma, were included in this randomized study to evaluate the merits of adrenalectomy as the primary mode of therapy as compared to the customary sequential hormonal manipulation. The 145 evaluable postmenopausal patients were randomized as follows: (1) primary additive hormone therapy first followed by adrenalectomy and (2) primary adrenalectomy followed by chemotherapy and/or additive hormone therapy. When 76 patients in group 1 were compared with 70 patients in group 2 regarding their survival time, there was no essential difference, but the response rate was 20% vs 38.