TLR4 Promotes and DAP12 Limits Obesity-Induced Osteoarthritis in Aged Female Mice.

Aging and female sex are the strongest risk factors for nontraumatic osteoarthritis (OA); whereas obesity is a modifiable risk factor accelerating OA. Prior studies indicate that the innate immune receptor toll-like receptor 4 (TLR4) mediates obesity-induced metabolic inflammation and cartilage catabolism via recognition of damage-associated molecular patterns and is increased with aging in OA joints. TLR4 responses are limited by innate immunoreceptor adapter protein DNAX-activating protein of 12kDA (DAP12).

Impact of α-adrenoceptor antagonists on prostate cancer development, progression and prevention.

Two decades following the discovery that α1-adrenoceptor antagonists suppress prostate tumor growth at the molecular and cellular level, the impact of α-blockade as re-purposed treatment strategy in the medical management of prostate cancer is gradually being recognized. Prostate cancer is the second most common cause of cancer deaths among males in the United States, yet the disease maintains inconsistent recommendations for prevention and screening. The functional relationship between α-adrenergic signaling and smooth muscle cells in the stroma of the prostate gland and the bladder neck empowered the use of α-adrenoceptor antagonists for the relief of urethral obstruction and clinical symptoms associated with benign prostatic hyperplasia (BPH).

Transcriptome and phenotyping analyses support a role for chloroplast sigma factor 2 in red-light-dependent regulation of growth, stress, and photosynthesis.

Sigma factor (SIG) proteins contribute to promoter specificity of the plastid-encoded RNA polymerase during chloroplast genome transcription. All six members of the SIG family, that is, SIG1-SIG6, are nuclear-encoded proteins targeted to chloroplasts. Sigma factor 2 (SIG2) is a phytochrome-regulated protein important for stoichiometric control of the expression of plastid- and nuclear-encoded genes that impact plastid development and plant growth and development.

Valence and magnitude ambiguity in feedback processing.

Background: Outcome feedback which indicates behavioral consequences are crucial for reinforcement learning and environmental adaptation. Nevertheless, outcome information in daily life is often totally or partially ambiguous. Studying how people interpret this kind of information would provide important knowledge about the human evaluative system.

Trait Anxiety and Economic Risk Avoidance Are Not Necessarily Associated: Evidence from the Framing Effect.

According to previous literature, trait anxiety is related to the tendency to choose safety options during risk decision-making, that is, risk avoidance. In our opinion, anxious people's risk preference might actually reflect their hypersensitivity to emotional information. To examine this hypothesis, a decision-making task that could elicit the framing effect was employed.

Melanocortin 1 Receptor: Structure, Function, and Regulation.

The melanocortin 1 receptor (MC1R) is a melanocytic Gs protein coupled receptor that regulates skin pigmentation, UV responses, and melanoma risk. It is a highly polymorphic gene, and loss of function correlates with a fair, UV-sensitive, and melanoma-prone phenotype due to defective epidermal melanization and sub-optimal DNA repair. MC1R signaling, achieved through adenylyl cyclase activation and generation of the second messenger cAMP, is hormonally controlled by the positive agonist melanocortin, the negative agonist agouti signaling protein, and the neutral antagonist β-defensin 3.

Peripheral (deep) but not periventricular MRI white matter hyperintensities are increased in clinical vascular dementia compared to Alzheimer's disease.

Background And Purpose: Vascular dementia (VAD) is a complex diagnosis at times difficult to distinguish from Alzheimer's disease (AD). MRI scans often show white matter hyperintensities (WMH) in both conditions. WMH increase with age, and both VAD and AD are associated with aging, thus presenting an attribution conundrum.

Therapeutic challenges in renal cell carcinoma.

Renal cell carcinoma (RCC) is a malignancy that in advanced disease, is highly resistant to systemic therapies. Elucidation of the angiogenesis pathways and their intrinsic signaling interactions with the genetic and metabolic disturbances within renal cell carcinoma variants has ushered in the era of "targeted therapies". Advanced surgical interventions and novel drugs targeting VEGF and mTOR, have improved patient survival and prolonged clinically stable-disease states.

Cytoskeleton targeting value in prostate cancer treatment.

Prostate cancer is a disease that affects hundreds of thousands of men in the United States each year. In the early stages of advanced prostate cancer, the disease can be suppressed by androgen deprivation therapy (ADT). Eventually, however, most patients experience resistance to androgen deprivation, and their treatment transitions to alternative targeting of the androgen axis with abiraterone and enzalutamide, as well as taxane-based chemotherapy.

Expression of peroxiredoxin 1 and 4 promotes human lung cancer malignancy.

Members of the Peroxiredoxin (Prx) family are major cellular antioxidants that scavenge hydrogen peroxide and play essential roles in oxidative stress and cell signaling. 2-Cys Prxs, including Prx1, 2, 3 and 4, have been indicated in multiple oncogenic signaling pathways and thus may contribute to various processes of cancer development. The significance of 2-Cys Prxs in lung cancer development and their biological function in signal transduction have not been fully investigated.

Linking brain electrical signals elicited by current outcomes with future risk decision-making.

The experience of current outcomes influences future decisions in various ways. The neural mechanism of this phenomenon may help to clarify the determinants of decision-making. In this study, thirty-nine young adults finished a risky gambling task by choosing between a high- and a low-risk option in each trial during electroencephalographic data collection.

Oral rehydration solutions for burn management in the field and underdeveloped regions: a review.

Burn injuries are the fourth most common type of trauma worldwide, and the appropriate care of burn injuries in resource-limited settings such as the battlefield, underdeveloped nations, or in mass casualtiesremains a significant challenge. Rehydration constitutes the primary treatment of the systemic effects of burns and is a major factor in patient recovery. The standard of care for the replenishment of fluid and electrolyte losses in burn injury remains intravenous fluid therapy, but oral rehydration solution therapy (ORST) demonstrates beneficial utility in saving the lives of burn patients when they are applied in the acute phase of burn injuries, especially when intravenous rehydration is unavailable or inaccessible.

Rapid Glucocorticoid-Induced Activation of TRP and CB1 Receptors Causes Biphasic Modulation of Glutamate Release in Gastric-Related Hypothalamic Preautonomic Neurons.

Glucocorticoids rapidly regulate synaptic input to neuroendocrine cells in the hypothalamic paraventricular nucleus (PVN) by inducing the retrograde release of endogenous messengers. Here we investigated the rapid effects of dexamethasone (DEX) on excitatory synaptic input to feeding-related, preautonomic PVN neurons using whole-cell patch-clamp recordings. In ∼50% of identified gastric-related preautonomic PVN neurons, DEX elicited a biphasic synaptic response characterized by an initial rapid and transient increase in the frequency of miniature excitatory postsynaptic currents (mEPSCs), followed by a decrease in mEPSC frequency within 9 min; remaining cells displayed only a decrease in mEPSC frequency.

Multiple regulatory mechanisms control B-1 B cell activation.

B-1 cells constitute a unique subset of B cells identified in several species including mice and humans. B-1 cells are further subdivided into B-1a and B-1b subsets as the former but not the later express CD5. The B-1a subset contributes to innate type of immune responses while the B-1b B cell subset contributes to adaptive responses.

Longitudinal analysis of arterial blood pressure and heart rate response to acute behavioral stress in rats with type 1 diabetes mellitus and in age-matched controls.

We recorded via telemetry the arterial blood pressure (BP) and heart rate (HR) response to classical conditioning following the spontaneous onset of autoimmune diabetes in BBDP/Wor rats vs. age-matched, diabetes-resistant control (BBDR/Wor) rats. Our purpose was to evaluate the autonomic regulatory responses to an acute stress in a diabetic state of up to 12 months duration.

The Differential Effect of Toxoplasma Gondii Infection on the Stability of BCL2-Family Members Involves Multiple Activities.

The regulation of mitochondrial permeability, a key event in the initiation of apoptosis is governed by the opposing actions of the pro- and anti-apoptotic members of the BCL2-family of proteins. The BCL2-family can be classified further based on the number of BCL-homology (BH) domains they encode. Pathogen mediated modulation of BCL2-family members play a significant role in their ability to affect the apoptotic pathways in the infected host cell.

Lithium-mediated protection against ethanol neurotoxicity.

Lithium has long been used as a mood stabilizer in the treatment of manic-depressive (bipolar) disorder. Recent studies suggest that lithium has neuroprotective properties and may be useful in the treatment of acute brain injuries such as ischemia and chronic neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, Huntington's disease and amyotrophic lateral sclerosis. One of the most important neuroprotective properties of lithium is its anti-apoptotic action.

Medical School Performance, Alumni Membership, and Giving: How Do Scholarship Recipients and Non-Recipients Differ?

Purpose: This study examines student recipients of merit, need-based, service, or minority scholarships, their performance in medical school, and the relationship to future alumni association membership and financial giving.

Method: Retrospective data on grade-point average attained across the four-year curriculum and extracurricular activities reported at graduation were collected on students at the University of Kentucky College of Medicine from 1981-1991. Comparisons of academic performance and participation in institutional activities were made across scholarship recipients and non-recipients.

Practices and Perceptions of Family Practice Residency Directors toward International Medical Graduate Applicants: A National Survey.

Purpose - International Medical Graduates (IMGs) are increasingly filling Family Medicine residency positions. (1) To what extent are residency programs recruiting and accepting IMG applicants? (2) What are program directors' perceptions of IMG applicants? (3) What program characteristics are associated with their practices and perceptions? Methods - A 2002 national survey of Family Medicine program directors assessed program demographics and directors' recruiting practices and perceptions regarding IMG applicants. Results - Although 88% of respondents would rank IMG applicants, only 40% agreed that they would perform as well as U.

Thrombosis of sirolimus-eluting coronary stent in the postanesthesia care unit.

A 44-yr-old woman with a drug-eluting coronary stent placement two weeks before surgery suffered a myocardial infarction in the postanesthesia care unit immediately after hysterectomy. She had missed only one dose of aspirin and clopidogrel preoperatively. Early recognition of subacute stent thrombosis and urgent percutaneous coronary intervention probably prevented her death.

Sleep medicine practices, training, and attitudes: a wake-up call for pulmonologists.

Study Objectives: To determine attitudes and knowledge about sleep medicine among chest physicians.

Design: : Interactive survey of self-selected respondents.

Setting: Interactive session at the 1998 American College of Chest Physicians (ACCP) annual meeting.