The COP9 signalosome is required for autophagy, proteasome-mediated proteolysis, and cardiomyocyte survival in adult mice.

Background: The COP9 signalosome (CSN) is an evolutionarily conserved protein complex composed of 8 unique protein subunits (CSN1 through CSN8). We have recently discovered in perinatal mouse hearts that CSN regulates not only proteasome-mediated proteolysis but also macroautophagy. However, the physiological significance of CSN in a post-mitotic organ of adult vertebrates has not been determined.

Hepatic deficiency of COP9 signalosome subunit 8 induces ubiquitin-proteasome system impairment and Bim-mediated apoptosis in murine livers.

The COP9 signalosome (CSN), an evolutionally highly conserved protein complex composed of 8 unique subunits (CSN1 through CSN8) in higher eukaryotes, is purported to modulate protein degradation mediated by the ubiquitin-proteasome system (UPS) but this has not been demonstrated in a critical mitotic parenchymal organ of vertebrates. Hepatocyte-specific knockout of the Cops8 gene (HS-Csn8KO) was shown to cause massive hepatocyte apoptosis and liver malfunction but the underlying mechanism remains unclear. Here, we report that Csn8/CSN exerts profound impacts on hepatic UPS function and is critical to the stability of the pro-apoptotic protein Bim.

A comparative study of the effects of vitamin C, sirolimus, and paclitaxel on the growth of endothelial and smooth muscle cells for cardiovascular medical device applications.

Antiproliferative drugs such as sirolimus (SIR) and paclitaxel (PAT) are currently released from stents and vascular grafts to inhibit the growth of smooth muscle cells (SMCs), thereby preventing neointimal hyperplasia. However, these drugs delay or impair the growth of endothelial cells (ECs) on implant surfaces causing late thrombosis. Hence, there is a need to use alternative drugs in these implants to encourage the growth of ECs and to inhibit the growth of SMCs.

Effectiveness of the emergency response course in improving student physical therapists' and licensed physical therapists' decision-making related to acute sports injuries and medical conditions.

Purpose: To analyze the effectiveness of the American Red Cross Emergency Response Course (ARC ERC) in improving decision-making skills of physical therapists (PTs) and third semester clinical doctorate student physical therapists (SPTs) when assessing acute sports injuries and medical conditions.

Methods: An existing questionnaire was modified, with permission from the original authors of the instrument. The questionnaire was administered to PTs and SPTs before the start of and immediately after the completion of 5 different ARC ERCs.

Effects of estradiol on transcriptional profiles in atherosclerotic iliac arteries in ovariectomized cynomolgus macaques.

Objective: This study aimed to assess the in vivo effects of estradiol treatment on arterial gene expression in atherosclerotic postmenopausal female monkeys.

Methods: Eight ovariectomized cynomolgus monkeys were fed atherogenic diets for 6.5 years.

Transcriptional regulation of a bacteriophage encoded extracellular DNase (Spd-3) by Rgg in Streptococcus pyogenes.

The Streptococcus pyogenes transcriptional regulator Rgg controls the expression of virulence-associated genes encoded both within the core genome and within horizontally transmissible DNA such as temperate bacteriophage. Previously, we showed that Rgg binds to the non-coding DNA upstream of the bacteriophage gene encoding an extracellular DNase Spd-3. In the current study, we further characterized Rgg-mediated regulation of spd-3 expression.

Vaccinating through a lifetime: adult priorities.

Vaccination strategies for adults have recently been updated to include newer vaccine products and to reflect the changing epidemiology of vaccine-preventable diseases in adults. New products include vaccines against shingles and the human papillomavirus, and a combination vaccine which contains an acellular pertussis component (Tdap). In some cases, existing vaccines have been re-formulated to provide alternate routes of delivery, as is the case with the influenza vaccine, or more effective formulations, as is the case with the meningococcal vaccine.

I don't know how I feel, therefore I act: alexithymia, urgency, and alcohol problems.

This study examined the relationships between alexithymia, impulsivity, and alcohol use and related problems. The sample consisted of 429 undergraduate students who reported drinking alcohol at least once in the past 3 months. Negative urgency mediated the relationship between alexithymia and alcohol-related problems, whereas positive urgency mediated the relationship between alexithymia and alcohol consumption.

Cytostasis and morphological changes induced by mifepristone in human metastatic cancer cells involve cytoskeletal filamentous actin reorganization and impairment of cell adhesion dynamics.

Background: Changes in cell shape and plasticity in cytoskeletal dynamics are critically involved in cell adhesion, migration, invasion and the overall process of metastasis. Previous work in our laboratory demonstrated that the synthetic steroid mifepristone inhibited the growth of highly metastatic cancer cells, while simultaneously causing striking changes in cellular morphology. Here we assessed whether such morphological alterations developed in response to cytostatic concentrations of mifepristone are reversible or permanent, involve rearrangement of cytoskeletal proteins, and/or affect the adhesive capacity of the cells.

Posttranslational modification and quality control.

Protein quality control functions to minimize the level and toxicity of misfolded proteins in the cell. Protein quality control is performed by intricate collaboration among chaperones and target protein degradation. The latter is performed primarily by the ubiquitin-proteasome system and perhaps autophagy.

Use of intraoperative duplex ultrasonography for identification and patch repair of kinking stenosis after carotid endarterectomy: a single-surgeon retrospective experience.

Objective: To provide an incidence and descriptive evaluation of kinking of the internal carotid artery (ICA) after carotid endarterectomy (CEA) in a consecutive CEA series that included the use of intraoperative duplex ultrasonography (IDUS) monitoring and to determine the effect of kink patch repair on long-term postoperative ICA restenosis.

Methods: The electronic medical records and IDUS recordings of all CEA cases performed over a 10-year period (March 2000 to October 2010) by a single neurosurgeon were retrospectively reviewed to assess cases of kinking after CEA.

Results: IDUS assisted in the identification of 27 of 285 cases (9.

Multiple functions of sushi domain containing 2 (SUSD2) in breast tumorigenesis.

Routinely used therapies are not adequate to treat the heterogeneity of breast cancer, and consequently, more therapeutic targets are desperately needed. To identify novel targets, we generated a breast cancer cDNA library enriched for genes that encode membrane and secreted proteins. From this library we identified SUSD2 (Sushi Domain Containing 2), which encodes an 822-amino acid protein containing a transmembrane domain and functional domains inherent to adhesion molecules.

Sani-cloth wipe mimics rare enzyme deficiency malonic aciduria on newborn screen.

Within a 7-month period at our institution, newborn screening by tandem mass spectrometry revealed 10 cases with elevated levels of malonylcarnitine, which suggested malonic aciduria. Malonic aciduria is a rare autosomal recessive inborn error of metabolism. Confirmatory testing yielded normal results in all the newborns involved.

Longstanding hyperthyroidism is associated with normal or enhanced intrinsic cardiomyocyte function despite decline in global cardiac function.

Thyroid hormones (THs) play a pivotal role in cardiac homeostasis. TH imbalances alter cardiac performance and ultimately cause cardiac dysfunction. Although short-term hyperthyroidism typically leads to heightened left ventricular (LV) contractility and improved hemodynamic parameters, chronic hyperthyroidism is associated with deleterious cardiac consequences including increased risk of arrhythmia, impaired cardiac reserve and exercise capacity, myocardial remodeling, and occasionally heart failure.

Ubiquitin receptors and protein quality control.

Protein quality control (PQC) is essential to intracellular proteostasis and is carried out by sophisticated collaboration between molecular chaperones and targeted protein degradation. The latter is performed by proteasome-mediated degradation, chaperone-mediated autophagy (CMA), and selective macroautophagy, and collectively serves as the final line of defense of PQC. Ubiquitination and subsequently ubiquitin (Ub) receptor proteins (e.

Healthy people, malaria and South Dakota.

The U.S. Department of Health and Human Services' Healthy People 2020 goals call for a reduction in the number of cases of malaria in the United States.

p62 Stages an interplay between the ubiquitin-proteasome system and autophagy in the heart of defense against proteotoxic stress.

As exemplified by desmin-related cardiomyopathy and myocardial ischemia/reperfusion injury, proteasome functional insufficiency plays an essential pathogenic role in the progression of cardiac diseases with elevated proteotoxic stress. Upregulation of p62/SQSTM1 and increased selective autophagy in cardiomyocytes may protect against proteotoxic stress in the heart. p62 may serve as a proteotoxic stress sensor, promote segregation and degradation of misfolded proteins by autophagy, and mediate the cross talk between the ubiquitin-proteasome system and autophagy.

Child maltreatment and deliberate self-harm among college students: testing mediation and moderation models for impulsivity.

This study examined the relationship between child maltreatment, impulsivity, and deliberate self-harm in a sample of college students. Four subtypes of impulsivity (urgency, premeditation, perseverance, and sensation seeking) were examined. Results show that participants who report child maltreatment histories also report higher levels of negative affect and higher levels of impulsivity, specifically negative urgency.

Long-term retention of information across the undergraduate medical school curriculum.

Medical school curricula must teach information to be mastered and retained for future clinical applicability. This study evaluated retention of knowledge across four years of medical education comparing two educational models. Clinical application and spaced learning may lead to better retention across all of medical school.

What happened to WHI: menopausal hormonal therapy in 2012.

Menopause is characterized by amenorrhea for 1 year due to the cessation of ovarian function. The hormonal treatment of menopause has significantly altered since the publication of initial results from the Women's Health Initiative continuous, combined, conjugated equine estrogen with medroxyprogesterone acetate study arm in 2002. Current studies suggest that treatment should be individualized and that the lowest dose of estrogen providing relief should be used for the shortest period of time in menopausal women who experience vasomotor symptoms or urogenital atrophy.

Trait-based affective processes in alcohol-involved "risk behaviors".

This study tested a theoretical model of alcohol use, markers of extreme intoxication, and risk behavior as a function of trait affect, distress tolerance, and affect-based behavior dysregulation. Positive affective pathways to risk behavior were primarily expected to be indirect via high levels of alcohol use, while negative affect paths were expected to be more directly associated with engagement in risk behavior. In addition, we expected trait affectivity and distress tolerance would primarily exhibit relationships with alcohol use and problems through behavioral dysregulation occurring during extreme affective states.

Characterization of a porcine intestinal epithelial cell line for influenza virus production.

We have developed a porcine intestine epithelial cell line, designated SD-PJEC for the propagation of influenza viruses. The SD-PJEC cell line is a subclone of the IPEC-J2 cell line, which was originally derived from newborn piglet jejunum. Our results demonstrate that SD-PJEC is a cell line of epithelial origin that preferentially expresses receptors of oligosaccharides with Sia2-6Gal modification.