Grouping behavior in a Triassic marine apex predator.

Marine tetrapods occupy important roles in modern marine ecosystems and often gather in large aggregations driven by patchy prey distribution,1,2 social or reproductive behaviors,3,4 or oceanographic factors.5 Here, we show that similar grouping behaviors evolved in an early marine tetrapod lineage, documented by dozens of specimens of the giant ichthyosaur Shonisaurus in the Luning Formation in West Union Canyon, Nevada, USA.6,7 A concentration of at least seven skeletons closely preserved on a single bedding plane received the bulk of previous attention. However, many more specimens are preserved across ∼106 square meters and ∼200 stratigraphic meters of outcrop representing an estimated >105-6 years. Unlike other marine-tetrapod-rich deposits, this assemblage is essentially monotaxic; other vertebrate fossils are exceptionally scarce. Large individuals are disproportionately abundant, with the exception of multiple neonatal or embryonic specimens, indicating an unusual demographic composition apparently lacking intermediate-sized juveniles or subadults. Combined with geological evidence, our data suggest that dense aggregations of Shonisaurus inhabited this moderately deep, low-diversity, tropical marine environment for millennia during the latest Carnian Stage of the Late Triassic Period (237-227 Ma). Thus, philopatric grouping behavior in marine tetrapods, potentially linked to reproductive activity, has an antiquity of at least 230 million years.

Defining osteoblast and adipocyte lineages in the bone marrow.

Bone is a complex endocrine organ that facilitates structural support, protection to vital organs, sites for hematopoiesis, and calcium homeostasis. The bone marrow microenvironment is a heterogeneous niche consisting of multipotent musculoskeletal and hematopoietic progenitors and their derivative terminal cell types. Amongst these progenitors, bone marrow mesenchymal stem/stromal cells (BMSCs) may differentiate into osteogenic, adipogenic, myogenic, and chondrogenic lineages to support musculoskeletal development as well as tissue homeostasis, regeneration and repair during adulthood. With age, the commitment of BMSCs to osteogenesis slows, bone formation decreases, fracture risk rises, and marrow adiposity increases. An unresolved question is whether osteogenesis and adipogenesis are co-regulated in the bone marrow. Osteogenesis and adipogenesis are controlled by specific signaling mechanisms, circulating cytokines, and transcription factors such as Runx2 and Pparγ, respectively. One hypothesis is that adipogenesis is the default pathway if osteogenic stimuli are absent. However, recent work revealed that Runx2 and Osx1-expressing preosteoblasts form lipid droplets under pathological and aging conditions. Histone deacetylase 3 (Hdac3) and other epigenetic regulators suppress lipid storage in preosteoblasts and/or control marrow adiposity. Establishing a better understanding of fat storage in bone marrow cells, as well as the osteoblast-adipocyte relationship within the bone marrow niche is necessary to understand the mechanisms underlying disease- and aging-related marrow fat storage and may lead to the development of new therapeutic targets for "fatty bone" and osteoporosis.

Mercury evidence for pulsed volcanism during the end-Triassic mass extinction.

The Central Atlantic Magmatic Province (CAMP) has long been proposed as having a causal relationship with the end-Triassic extinction event (∼201.5 Ma). In North America and northern Africa, CAMP is preserved as multiple basaltic units interbedded with uppermost Triassic to lowermost Jurassic sediments. However, it has been unclear whether this apparent pulsing was a local feature, or if pulses in the intensity of CAMP volcanism characterized the emplacement of the province as a whole. Here, six geographically widespread Triassic-Jurassic records, representing varied paleoenvironments, are analyzed for mercury (Hg) concentrations and Hg/total organic carbon (Hg/TOC) ratios. Volcanism is a major source of mercury to the modern environment. Clear increases in Hg and Hg/TOC are observed at the end-Triassic extinction horizon, confirming that a volcanically induced global Hg cycle perturbation occurred at that time. The established correlation between the extinction horizon and lowest CAMP basalts allows this sedimentary Hg excursion to be stratigraphically tied to a specific flood basalt unit, strengthening the case for volcanic Hg as the driver of sedimentary Hg/TOC spikes. Additional Hg/TOC peaks are also documented between the extinction horizon and the Triassic-Jurassic boundary (separated by ∼200 ky), supporting pulsatory intensity of CAMP volcanism across the entire province and providing direct evidence for episodic volatile release during the initial stages of CAMP emplacement. Pulsatory volcanism, and associated perturbations in the ocean-atmosphere system, likely had profound implications for the rate and magnitude of the end-Triassic mass extinction and subsequent biotic recovery.

Phlpp1 facilitates post-traumatic osteoarthritis and is induced by inflammation and promoter demethylation in human osteoarthritis.

OBJECTIVE: Osteoarthritis (OA) is the most common form of arthritis and a leading cause of disability. OA is characterized by articular chondrocyte deterioration, subchondral bone changes and debilitating pain. One strategy to promote cartilage regeneration and repair is to accelerate proliferation and matrix production of articular chondrocytes. We previously reported that the protein phosphatase Phlpp1 controls chondrocyte differentiation by regulating the activities of anabolic kinases. Here we examined the role of Phlpp1 in OA progression in a murine model. We also assessed PHLPP1 expression and promoter methylation. DESIGN: Knee joints of WT and Phlpp1(-/-) mice were surgically destabilized by transection of the medial meniscal ligament (DMM). Mice were assessed for signs of OA progression via radiographic and histological analyses, and pain assessment for mechanical hypersensitivity using the von Frey assay. Methylation of the PHLPP1 promoter and PHLPP1 expression were evaluated in human articular cartilage and chondrocyte cell lines. RESULTS: Following DMM surgeries, Phlpp1 deficient mice showed fewer signs of OA and cartilage degeneration. Mechanical allodynia associated with DMM surgeries was also attenuated in Phlpp1(-/-) mice. PHLPP1 was highly expressed in human articular cartilage from OA patients, but was undetectable in cartilage specimens from femoral neck fractures (FNFxs). Higher PHLPP1 levels correlated with less PHLPP1 promoter CpG methylation in cartilage from OA patients. Blocking cytosine methylation or treatment with inflammatory mediators enhanced PHLPP1 expression in human chondrocyte cell lines. CONCLUSION: Phlpp1 deficiency protects against OA progression while CpG demethylation and inflammatory cytokines promote PHLPP1 expression.

Progressive disseminated histoplasmosis presenting as cellulitis in a renal transplant recipient.

With the advent of potent immunosuppressive therapies used in solid organ transplantation, patients are more susceptible to a variety of infectious organisms. Infections may result from atypical pathogens and present in an unusual manner. We describe a case of progressive disseminated histoplasmosis presenting as cellulitis in a renal transplant recipient and review this disease.

Cardiac tamponade complicating myocardial infarction in the era of thrombolytics and platelet IIb/IIIa: case report and literature review.

Pericardial tamponade is a rare complication of acute myocardial infarction. The authors present the case of a patient with a large anterior myocardial infarction administered thrombolytics who developed postinfarction pericarditis. Because of a stuttering course with concomitant postinfarction angina, urgent angiography, leading to percutaneous transluminal coronary angioplasty and stent implantation, was performed. Administration of abciximab prior to percutaneous transluminal coronary angioplasty appears to have precipitated pericardial tamponade. The authors review the literature concerning numerous commonly utilized therapeutic options that could have contributed to the development of pericardial tamponade.

The impact of outcomes data reporting on access to health care of high-risk patients to interventional cardiologists in the United States.

BACKGROUND: Pressure is increasingly being placed on medical sub-specialists to lower procedural costs while improving overall outcomes. Outcomes data reporting has been utilized in an attempt to improve procedural results; however, some negative aspects of this type of reporting have emerged. METHODS: We surveyed 5,229 interventional cardiologists practicing in the United States regarding the effect of outcomes data reporting on their approach to high-risk patients who required interventional procedures. The results were analyzed one month after mailing the survey. RESULTS: One thousand, four hundred and forty-four cardiologists responded to the survey. Ninety-three percent of the respondents indicated that outcomes data reporting would have some effect on their approach to high-risk patients. Only 7% said outcomes reporting would have no effect on their willingness to perform interventions on high-risk patients. The majority of respondents performed between 51 and 100 interventions per year; those who performed more than 500 interventions per year reported that they would be less affected if outcomes data were reported from their results. CONCLUSIONS: Our survey indicates that outcomes data reporting would have a significant effect on the willingness of cardiologists to perform procedures on high-risk patients; this effect may limit access to needed care for this high-risk population.

Usefulness of positive troponin-T and negative creatine kinase levels in identifying high-risk patients with unstable angina pectoris.

Troponin-T was measured in patients with chest pain and negative creatine phosphokinase-MB isoenzymes. Patients with elevated troponin-T had a significantly greater risk of cardiac events over the next 6 months than patients with normal troponin-T.

Progressive systemic sclerosis causing rapidly progressive myocardial disease and death.

We have presented an unusually swift progression of progressive systemic sclerosis (PSS), with death from cardiogenic shock in a 22-year-old woman who had severe hypertension and acute renal insufficiency. She arrived at our hospital with pericardial tamponade and shock. Despite initial improvement after pericardiocentesis, the patient's condition soon deteriorated and she died of cardiogenic shock. PSS was diagnosed at autopsy. Although the course of PSS is frequently indolent, it may also be fulminant, leading to death before diagnosis is determined.

Inpatient cardiopulmonary resuscitation: is survival prediction possible?

We retrospectively reviewed 443 patients who had cardiopulmonary resuscitation (CPR). The focus of the study was to discover what preexisting factors should be assessed to determine the probability of survival. There were 88 successes out of 340 cases (25.9%). The absence of a previous myocardial infarction (MI), shock, partial pressure of oxygen (PaO2) less than 60 mm Hg, blood urea nitrogen (BUN) level greater than 20 mg/dL, pneumonia, pulmonary edema, and oliguria were found to predict a successful outcome. Logistic regression was used to predict percentage of successes in the various groups of patients with various clinical characteristics. The observed and predicted numbers of successes were in close agreement in most cases. We also constructed a classification function to predict whether an individual subject would survive the event for which CPR was required. Sixty-seven of the 88 observed successes would have been predicted, for an estimated sensitivity of 76%, and 164 of the 252 failures would have been predicted, for an estimated specificity of 65%. A large percentage (24%) of cases in which the patient actually survived CPR would have been predicted to be failures. We conclude that preexisting factors before a cardiopulmonary arrest do not accurately predict survival after CPR.

Dominant role of circulating catecholamines in the myocardial contractile response to intravenous nicotine.

Experiments were conducted in anesthetized dogs to determine the mechanism primarily responsible for the increase in myocardial contractile function during intravenous infusion of nicotine. Myocardial function was assessed regionally by measuring segment shortening using ultrasonic dimension gauges. The role of cardiac neural stimulation in the absence of direct effects of nicotine and other circulating factors was evaluated by perfusing a region of left ventricular myocardium with blood from a reservoir during systemic nicotine infusion. Segment shortening increased from 11 to 19% in normally perfused myocardium but deteriorated to nearly 0% in reservoir-perfused myocardium. To evaluate direct effects of nicotine on cardiac function, nicotine was infused directly into a perfused coronary artery. An intracoronary concentration of nicotine equivalent to that caused by intravenous administration (0.69 +/- 0.08 micrograms/ml plasma) had no effect on myocardial contractile function. An intracoronary nicotine concentration of 5 micrograms/ml was required to directly increase contractile function to approximately the same extent observed during intravenous nicotine. To evaluate the role of circulating catecholamines in the myocardial response to intravenous nicotine, observations were made before and after bilateral adrenalectomy. Adrenalectomy markedly attenuated the pressor response to intravenous nicotine and abolished the positive cardiac inotropic response. We conclude that the adrenal release of catecholamines is primarily responsible for increased myocardial contractile function during intravenous nicotine.

Direct measurement of femtogram amounts of DNA in cells and chloroplasts by quantitative microspectrofluorometry.

Absolute DNA amounts of individual chloroplasts were determined by measuring the fluorescence intensity of chloroplasts stained with 4',6-diamidino-2-phenylindole (DAPI) relative to that of the bacterium Pediococcus damnosus (cerevisiae) smeared on the same slide. An absolute DNA content of 7.7 X 10(15) g for a standard P. damnosus cell type was calculated by comparing the relative fluorescence values and frequency of each stage of cellular development in a culture to the average DNA content of all cell types determined by chemical methods. Chlorophyll was extracted from the chloroplasts during fixation so that chlorophyll autofluorescence was not present when DAPI fluorescence was measured. Absolute amounts of DNA could then be determined for single chloroplasts, either within cells that were individually selected from a mixed cell population or in small preparations of isolated chloroplasts. The DNA amounts of chloroplasts from mesophyll cells determined in this way were similar to the values previously determined by bulk averaging methods. Chloroplast DNA amounts from different cell types of the leaf could be measured by microspectrofluorometry, and it was found that chloroplasts from spinach epidermal cells contained about half as much DNA as chloroplasts from adjacent mesophyll cells.

Microspectrofluorometric Measurement of Chloroplast DNA in Dividing and Expanding Leaf Cells of Spinacia oleracea.

Absolute DNA amounts of individual chloroplasts from mesophyll and epidermal cells of developing spinach leaves were measured by microspectrofluorometry using the DNA-specific stain, 4,6-diamidino-2-phenyl indole, and the bacterium, Pediococcus damnosus, as an internal standard. Values obtained by this method showed that DNA amounts of individual chloroplasts from mesophyll cells fell within a normal distribution curve, although mean DNA amounts changed during leaf development and also differed from the levels in epidermal chloroplasts. There was no evidence in the data of plastids containing either the high or low levels of DNA which would be indicative of discontinuous polyploidy of plastids, or of division occurring in only a small subpopulation of chloroplasts. By contrast, the distribution of nuclear DNA amounts in the same leaf tissues in which cell division was known to be occurring showed a clear bimodal distribution. We consider that the distribution of chloroplast DNA in the plastid population shows that there is no S-phase of chloroplast DNA synthesis, all chloroplasts in the population in young leaf cells synthesize DNA, and all chloroplasts divide.