Subtelomere-binding protein Tbf1 and telomere-binding protein Rap1 collaborate to inhibit localization of the Mre11 complex to DNA ends in budding yeast.

Chromosome ends, known as telomeres, have to be distinguished from DNA double-strand breaks that activate DNA damage checkpoints. In budding yeast, the Mre11-Rad50-Xrs2 (MRX) complex associates with DNA ends and promotes checkpoint activation. Rap1 binds to double-stranded telomeric regions and recruits Rif1 and Rif2 to telomeres.

Biobrane in the management of critical microsurgical wounds of the upper extremity.

Purpose: Evolving soft tissue necrosis and/or edema can complicate microsurgical reconstruction by leading to open wounds with exposure of critical structures: anastamosed vessels, nerves, and tendons. Not infrequently, primary closure of these wounds is not possible. Immediate skin grafting may lead to anatomical and/or functional failure of reconstructed structures, compromising immediate or long-term functional outcomes.

Treatment of a supratentorial primitive neuroectodermal tumor using magnetic resonance-guided laser-induced thermal therapy.

Supratentorial primitive neuroectodermal tumors (PNETs) are rare tumors that carry a poorer prognosis than those arising from the infratentorial compartment (such as medulloblastoma). The overall prognosis for these patients depends on several factors including the extent of resection, age at diagnosis, CSF dissemination, and site in the supratentorial space. The authors present the first case of a patient with a newly diagnosed supratentorial PNET in which cytoreduction was achieved with MR-guided laser-induced thermal therapy.

Dietary fructose inhibits lactation-induced adaptations in rat 1,25-(OH)₂D₃ synthesis and calcium transport.

We recently showed that excessive fructose consumption, already associated with numerous metabolic abnormalities, reduces rates of intestinal Ca(2+) transport. Using a rat lactation model with increased Ca(2+) requirements, we tested the hypothesis that mechanisms underlying these inhibitory effects of fructose involve reductions in renal synthesis of 1,25-(OH)(2)D(3). Pregnant and virgin (control) rats were fed isocaloric fructose or, as controls, glucose, and starch diets from d 2 of gestation to the end of lactation.

Moving from the laboratory bench to patients' bedside: considerations for effective therapy with stem cells.

Although stem cell therapy is not a new field, the field was limited to transplantation of hematopoietic stem cells. Such transplantation has provided invaluable information for the emerging field with new stem cells. Mesenchymal stem cells (MSCs) are an attractive source for therapy; reduced ethical concern, ease in expansion, as off-the-shelf stem cells.

Treatment of adult obesity with bariatric surgery.

Bariatric surgery procedures, including laparoscopic adjustable gastric banding, laparoscopic sleeve gastrectomy, and Roux-en-Y gastric bypass, result in an average weight loss of 50 percent of excess body weight. Remission of diabetes mellitus occurs in approximately 80 percent of patients after Roux-en-Y gastric bypass. Other obesity-related comorbidities are greatly reduced, and health-related quality of life improves.

Decrease in phosphatidylinositol 4,5-bisphosphate levels mediates desensitization of the cold sensor TRPM8 channels.

The activity of the cold- and menthol-activated transient receptor potential melastatin 8 (TRPM8) channels diminishes over time in the presence of extracellular Ca(2+), a phenomenon referred to as desensitization or adaptation. Here we show that activation of TRPM8 by cold or menthol evokes a decrease in cellular phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P(2)] levels. The decrease in PtdIns(4,5)P(2) levels was accompanied by increased inositol 1,4,5 trisphosphate (InsP(3)) production, and was inhibited by loading the cells with the Ca(2+) chelator BAPTA-AM, showing that it was the consequence of the activation of phospholipase C (PLC) by increased intracellular Ca(2+) concentrations.

Collagen expression in the pregnant human cervix is decreased with labor.

Objective: The current study tested the hypothesis that collagen content in the pregnant cervix decreases with labor, using morphologically preserved specimens, avoiding limitations of earlier studies. Collagen abundance remote from pregnancy was also evaluated.

Materials And Methods: Histologic sections of postpartum cervix obtained from 22 cases of total hysterectomy performed immediately after delivery: 13 cases performed after delivery with no labor and 9 cases in which labor had ensued before delivery.

Vulnerable Groups Living with Spinal Cord Injury.

There is considerable variation in rehabilitation outcomes within the population of spinal cord-injured individuals across racial and socioeconomic groups. This suggests that the long-term health following spinal cord injury (SCI) is determined, at least in part, by group differences in exposure to advantages and disadvantages among persons living in the community. This article conceptualizes the nature of vulnerability and how increased vulnerability leads to disparities in SCI outcomes.

Vaginal blue nevus: report of a case and review of the literature.

Objective: : Blue nevi are extremely rare in the vaginal canal and are suspicious for melanoma, especially when multiple lesions are present. We describe a woman with multiple blue nevi of the vagina.

Design: : We describe 1 case of multiple blue nevi of the vagina.

Self-reported non-adherence to immune-suppressant therapy in liver transplant recipients: demographic, interpersonal, and intrapersonal factors.

Adherence to immune suppressants and follow-up care regimen is important in achieving optimal long-term outcomes after organ transplantation. To identify patients most at risk for non-adherence, this cross-sectional, descriptive study explores the prevalence and correlates of non-adherence to immune-suppressant therapy among liver recipients. Anonymous questionnaires mailed consisted of the domains: (i) adherence barriers to immune suppressants, (ii) immune suppressants knowledge, (iii) demographics, (iv) social support, (v) medical co-morbidities, and (vi) healthcare locus of control and other beliefs.

Identification of the radial nerve during the posterior approach to the humerus: a cadaveric study.

Objective: Identification of the radial nerve is necessary during the posterior approach to the humerus in an effort to maintain its integrity. Other than anatomic descriptions of the radial nerve with respect to osseous structures, there are few superficial intraoperative landmarks along the course of the traditional triceps-splitting approach to provide facile nerve identification. The objective of this study was to determine the reliability of using the anatomic intersection of the long and lateral heads of the triceps and the triceps aponeurosis as a superficial reference point for radial nerve identification during the posterior approach to the humerus.

Ecto-5'-nucleotidase (CD73) decreases mortality and organ injury in sepsis.

The extracellular concentrations of adenosine are increased during sepsis, and adenosine receptors regulate the host's response to sepsis. In this study, we investigated the role of the adenosine-generating ectoenzyme, ecto-5'-nucleotidase (CD73), in regulating immune and organ function during sepsis. Polymicrobial sepsis was induced by subjecting CD73 knockout (KO) and wild type (WT) mice to cecal ligation and puncture.

Trauma hemorrhagic shock-induced lung injury involves a gut-lymph-induced TLR4 pathway in mice.

Background: Injurious non-microbial factors released from the stressed gut during shocked states contribute to the development of acute lung injury (ALI) and multiple organ dysfunction syndrome (MODS). Since Toll-like receptors (TLR) act as sensors of tissue injury as well as microbial invasion and TLR4 signaling occurs in both sepsis and noninfectious models of ischemia/reperfusion (I/R) injury, we hypothesized that factors in the intestinal mesenteric lymph after trauma hemorrhagic shock (T/HS) mediate gut-induced lung injury via TLR4 activation.

Methods/principal Findings: The concept that factors in T/HS lymph exiting the gut recreates ALI is evidenced by our findings that the infusion of porcine lymph, collected from animals subjected to global T/HS injury, into naïve wildtype (WT) mice induced lung injury.

A second case of Marburg's variant of multiple sclerosis with vasculitis and extensive demyelination.

Marburg's variant of multiple sclerosis is a rapidly progressive and malignant form of multiple sclerosis (MS) that usually leads to severe disability or death within weeks to months without remission. Few cases have been described in the literature since the original description by Marburg. The classic pathological findings usually include highly destructive zones of extensive demyelination, necrosis with dense cellular infiltrate, and giant reactive astrocytes.

Leadership training for radiologists: a survey of opportunities and participants in MBA and MPH programs by medical students, residents, and current chairpersons.

Purpose: The aim of this study was to determine opportunities for students and trainees to obtain an MPH or MBA degree during either medical school or radiology residency and to determine the prevalence of such degree possession by chairpersons in radiology.

Methods: All allopathic medical schools in the United States were surveyed to chart the number of MD/MPH and MD/MBA degree programs available to students. Program directors were contacted to assess the number of MPH or MBA courses of study administratively related to their residencies.

The extracellular cAMP-adenosine pathway regulates expression of renal D1 dopamine receptors in diabetic rats.

Activation of D1 dopamine receptors expressed in the kidneys promotes the excretion of sodium and regulates sodium levels during increases in dietary sodium intake. A decrease in the expression or function of D1 receptors results in increased sodium retention which can potentially lead to the development of hypertension. Studies have shown that in the absence of functional D1 receptors, in null mice, the systolic, diastolic, and mean arterial pressures are higher.

Children with autism spectrum disorders (ASD) who exhibit chronic gastrointestinal (GI) symptoms and marked fluctuation of behavioral symptoms exhibit distinct innate immune abnormalities and transcriptional profiles of peripheral blood (PB) monocytes.

Innate/adaptive immune responses and transcript profiles of peripheral blood monocytes were studied in ASD children who exhibit fluctuating behavioral symptoms following infection and other immune insults (ASD/Inf, N=30). The ASD/Inf children with persistent gastrointestinal symptoms (ASD/Inf+GI, N=19), revealed less production of proinflammatory and counter-regulatory cytokines with stimuli of innate immunity and marked changes in transcript profiles of monocytes as compared to ASD/no-Inf (N=28) and normal (N=26) controls. This included a 4-5 fold up-regulation of chemokines (CCL2 and CCL7), consistent with the production of more CCL2 by ASD/Inf+GI cells.

Beta-blockade prevents hematopoietic progenitor cell suppression after hemorrhagic shock.

Background: Severe injury is accompanied by sympathetic stimulation that induces bone marrow (BM) dysfunction by both suppression of hematopoietic progenitor cell (HPC) growth and loss of cells via HPC mobilization to the peripheral circulation and sites of injury. Previous work demonstrated that beta-blockade (BB) given prior to tissue injury both reduces HPC mobilization and restores HPC colony growth within the BM. This study examined the effect and timing of BB on BM function in a hemorrhagic shock (HS) model.

Loco signaling pathway in longevity.

Despite the various roles of regulator of G protein signaling (RGS) protein in the G protein signaling pathway that have been defined, the function of RGS has not been characterized in longevity signaling pathways. We found that reduced expression of Loco, a Drosophila RGS protein, resulted in a longer lifespan of flies with stronger resistance to stress, higher MnSOD activity and increased fat content. In contrast, overexpression of the loco gene shortened the fly lifespan significantly, lowered stress resistance and reduced fat content, also indicating that the RGS domain containing GTPase-activating protein (GAP) activity is related to the regulation of longevity.

Evidence that phosphorylation by the mitotic kinase Cdk1 promotes ICER monoubiquitination and nuclear delocalization.

In contrast to normal prostatic cells, the transcriptional repressor Inducible cAMP Early Repressor (ICER) is undetected in the nuclei of prostate cancer cells. The molecular mechanisms for ICER abnormal expression in prostate cancer cells remained largely unknown. In this report data is presented demonstrating that ICER is phosphorylated by the mitotic kinase cdk1.

Functional significance of cytosolic endothelial nitric-oxide synthase (eNOS): regulation of hyperpermeability.

Endothelial NOS (eNOS)-derived NO is a key factor in regulating microvascular permeability. We demonstrated previously that eNOS translocation from the plasma membrane to the cytosol is required for hyperpermeability. Herein, we tested the hypothesis that eNOS activation in the cytosol is necessary for agonist-induced hyperpermeability.