Chondrocytic and pharmacokinetic properties of Phlpp inhibitors.

Objective: The pleckstrin homology domain leucine-rich repeat protein phosphatases (Phlpp1/2) were recently identified as potential therapeutic targets for cartilage regeneration in osteoarthritic joints. Phlpp inhibitors NSC 117079 and NSC 45586 increase chondrocyte proliferation and matrix production, but the pharmacodynamics and pharmacokinetics of these compounds are not known. Design: Chondrocytic effects of Phlpp inhibitors, NSC 117079 and NSC 45586, were measured by western blotting of Phlpp substrates, glycosaminoglycan (GAG) assays, and transcriptomic assays. Liquid chromatography/mass spectroscopy assays were established to measure NSC 117079 and NSC 45586 in vitro and in vivo. The effects of NSC 117079 and NSC 45586 on articular cartilage structure in vivo after intra-articular injection were determined by histology. Results: The Phlpp inhibitors NSC 117079 and NSC 45586 were highly stable in vitro and stimulated GAG, Sox9, proteoglycan 4 and collagen 2 production in maturing but not more differentiated chondrocytes in vitro. Both molecules reduced Phlpp1/2 levels and suppressed matrix degradation to functionally extend their inhibitory effect on these phosphatases. In vivo, NSC 117079 was eliminated from the bloodstream within 4 â€‹h after intravenous injection, while NSC 45586 was eliminated in 8 â€‹h and had a higher volume distribution. Both molecules increased articular cartilage area on lateral and medial tibial plateaus and femoral condyles by 15% in C57Bl/6 mice between four and five weeks of age. Conclusion: These data advance our understanding of how Phlpp inhibitors promote and preserve cartilage formation and provide a basis for understanding their safety and activity in vivo.

Direct Measurement of Single-Molecule Ligand-Receptor Interactions.

Measuring the kinetics that govern ligand-receptor interactions is fundamental to our understanding of pharmacology. For ligand-gated ion channels, binding of an agonist triggers allosteric motions that open an integral ion-permeable pore. By mathematically modeling stochastic electrophysiological responses with high temporal resolution (ms), previous single channel studies have been able to infer the rate constants of ligands binding to these receptors. However, there are no reports of the direct measurement of the single-molecule binding events that are vital to how agonists exert their functional effects. For the first time, we report these direct measurements, the rate constants, and corresponding free energy changes, which describe the transitions between the different binding states. To achieve this, we use the super resolution technique: points accumulation for imaging in nanoscale topography (PAINT) to observe binding of ATP to orthosteric binding sites on the P2X1 receptor. Furthermore, an analysis of time-resolved single-molecule interactions is used to measure elementary rate constants and thermodynamic forces that drive the allosteric motions. These single-molecule measurements unequivocally establish the location of each binding states of the P2X1 receptor and the stochastic nature of the interaction with its native ligand. The analysis leads to the measurement of the forward and reverse rates from a weak ligand-binding state to a strong ligand binding state that is linked to allosteric motion and ion pore formation. These rates (kα = 1.41 sec-1 and kß = 0.32 sec-1) were then used to determine the free energy associated with this critical mechanistic step (3.7 kJ/mol). Importantly, the described methods can be readily applied to all ligand-gated ion channels, and more broadly to the molecular interactions of other classes of membrane proteins.

The present is not the key to the past: a polar forest from the permian of antarctica.

An in situ Upper Permian fossil forest in the central Transantarctic Mountains near the Beardmore Glacier includes 15 permineralized trunks in growth position; the paleolatitude of the site was approximately 80 degrees to 85 degrees south. Numerous leaves of the seed fern Glossopteris are present in the shale in which the trunks are rooted. The trunks are permineralized and tree rings reveal that the forest was a rapidly growing and young forest, persisting in an equable, strongly seasonal climate-a scenario that does not fit with some climate reconstructions for this time period.

Microfilaments in cellular and developmental processes.

In our opinion, all of the phenomena that are inhibited by cytochalasin can be thought of as resulting from contractile activity of cellular organelles. Smooth muscle contraction, clot retraction, beat of heart cells, and shortening of the tadpole tail are all cases in which no argument of substance for alternative causes can be offered. The morphogenetic processes in epithelia, contractile ring function during cytokinesis, migration of cells on a substratum, and streaming in plant cells can be explained most simply on the basis of contractility being the causal event in each process. The many similarities between the latter cases and the former ones in which contraction is certain argue for that conclusion. For instance, platelets probably contract, possess a microfilament network, and behave like undulating membrane organelles. Migrating cells possess undulating membranes and contain a similar network. It is very likely, therefore, that their network is also contractile. In all of the cases that have been examined so far, microfilaments of some type are observed in the cells; furthermore, those filaments are at points where contractility could cause the respective phenomenon. The correlations from the cytochalasin experiments greatly strengthen the case; microfilaments are present in control and "recovered" cells and respective biological phenomena take place in such cells; microfilaments are absent or altered in treated cells and the phenomena do not occur. The evidence seems overwhelming that microfilaments are the contractile machinery of nonmuscle cells. The argument is further strengthened if we reconsider the list of processes insensitive to cytochalasin (Table 2). Microtubules and their sidearms, plasma membrane, or synthetic machinery of cells are presumed to be responsible for such processes, and colchicine, membrane-active drugs, or inhibitors of protein synthesis are effective at inhibiting the respective phenomena. These chemical agents would not necessarily be expected to affect contractile apparatuses over short periods of time, they either do not or only secondarily interfere with the processes sensitive to cytochalasin (Table 1). It is particularly noteworthy in this context that microtubules are classed as being insensitive to cytochalasin and so are not considered as members of the "contractile microfilament" family. The overall conclusion is that a broad spectrum of cellular and developmental processes are caused by contractile apparatuses that have at least the common feature of being sensitive to cytochalasin. Schroeder's important insight (3) has, then, led to the use of cytochalasin as a diagnostic tool for such contracile activity: the prediction is that sensitivity to the drug implies presence of some type of contractile microfilament system. Only further work will define the limits of confidence to be placed upon such diagnoses. The basis of contraction in microfilament systems is still hypothetical. Contraction of glycerol-extracted cells in response to adenosine triphosphate (53), extraction of actin-like or actomyosin-like proteins from cells other than muscle cells (54), and identification of activity resembling that of the actomyosin-adenosine triphosphatase system in a variety of nonmuscle tissues (40, 54) are consistent with the idea that portions of the complex, striated muscle contractile system may be present in more primitive contractile machinery. In the case of the egg cortex, calcium-activated contractions can be inhibited by cytochalasin. If, as seems likely, microfilaments are the agents activated by calcium, then it will be clear that they have the same calcium requirement as muscle. Biochemical analyses of primitive contractile systems are difficult to interpret. Ishikawa's important observation (31), that heavy meromyosin complexes with fine filaments oriented parallel to the surface of chondrocytes and perpendicular to the surface of intestinal epithelial cells, implies that both types of filaments are "actin-like" in this one respect. Yet, it is very likely that these actin-like filaments correspond respectively to the cytochalasin-insensitive sheath of glial and heart fibroblasts and the core filaments of oviduct microvilli. No evidence from our studies links contractility directly to these meromyosin-binding filaments. Apart from this problem, activity resembling that of the myosin-adenosine triphosphatase has been associated with the microtubule systems of sperm tails and cilia (55), but those organelles are insensitive to cytochalasin in structure and function. Clearly, a means must be found to distinguish between enzymatic activities associated with microfilament networks, microfilament bundles, microtubules, and the sheath filaments of migratory cells. Until such distinctions are possible, little of substance can be said about the molecular bases of primitive contractile systems. Three variables are important for the control of cellular processes dependent upon microfilaments: (i) which cells of a population shall manufacture and assemble the filaments; (ii) where filaments shall be assembled in cells; and (iii) when contractility shall occur. With respect to distribution among cells, the networks involved in cell locomotion are presumed to be present in all cells that have the potential to move in cell culture. In this respect, the networks can be regarded as a common cellular organelle in the sense that cytoplasmic microtubules are so regarded. In some developing systems, all cells of an epithelium possess microfilament bundles (7, 13), whereas, in others, only discrete subpopulations possess the bundles (5, 6). In these cases the filaments can be regarded as being differentiation products associated only with certain cell types. These considerations may be related to the fact that microfilament networks are associated with behavior of individual cells (such as migration, wound healing, and cytokinesis), whereas the bundles are present in cells that participate in coordinated changes in shape of cell populations. With respect to placement in cells, two alternatives are apparent, namely, localized or ubiquitous association with the plasma membrane. Microfilament bundles of epithelial cells are only found extending across the luminal and basal ends of cells. In this respect they contrast with desmosomal tonofilaments and with microtubules, each of which can curve in a variety of directions through the cell. The strict localization of microfilament bundles probably rests upon their association with special junctional complex insertion regions that are only located near the ends of cells. In the case of mitotically active cells, the orientation of the spindle apparatus may determine the site at which the contractile ring of microfilaments will form (4, 56); this raises the question of what sorts of cytoplasmic factors can influence the process of association between filament systems and plasma membranes. In contrast to such cases of localized distribution, contractile networks responsible for cell locomotion are probably found beneath all of the plasma membrane, just as the network of thrombosthenin may extend to all portions of the periphery of a blood platelet. This ubiquitous distribution probably accounts for the ability of a fibroblast or glial cell to establish an undulating membrane at any point on its edge, or of an axon to form lateral microspikes along its length. The third crucial aspect of control of these contractile apparatuses involves the choice of when contraction shall occur (and as a corollary the degree or strength of contraction that will occur). In the simplest situation, contraction would follow automatically upon assembly of the microfilament bundles or networks. In cleavage furrows of marine embryos (4), for instance, microfilaments are seen beneath the central cleavage furrow and at its ends, but not beyond, under the portion of plasma membrane that will subsequently become part of the furrow. This implies that the furrow forms very soon after the contractile filaments are assembled in the egg cortex. In other cases, microfilaments are apparently assembled but not in a state of (maximal?) contraction. Thus, networks are seen along the sides of migratory cells, although such regions are not then active as undulating membrane organelles. Similarly, microfilament bundles occur in all epithelial cells of the salivary gland (13), or pancreatic anlage (7), although only the ones at discrete points are thought to generate morphogenetic tissue movements. Likewise, bundles begin to appear as early as 12 hours after estrogen administration to oviduct, although visible tubular gland formation does not start until 24 to 30 hours. Finally, streaming in plant cells can wax and wane, depending upon external factors such as auxin (57). All of these cases imply a control mechanism other than mere assembly of the microfilament systems and even raise the possibility that within one cell some filaments may be contracting while others are not. In discussing this problem, it must be emphasized that different degrees of contraction or relaxation cannot as yet be recognized with the electron microscope. In fact, every one of the cases cited above could be explained by contraction following immediately upon some subtle sort of "assembly." Inclusive in the latter term are relations between individual filaments, relations of the filaments and their insertion points on plasma membrane, and quantitative alterations in filament systems. Furthermore, the critical role of calcium and high-energy compounds in muscle contraction suggest that equivalent factors may be part of primitive, cytochalasinsensitive systems. The finding that calcium-induced contraction in the cortex of eggs is sensitive to cytochalasin strengthens that supposition and emphasizes the importance of compartmentalization of cofactors as a means of controlling microfilaments in cells.

Combination of flavor enhancement and chemosensory education improves nutritional status in older cancer patients.

BACKGROUND: Abnormalities in taste and smell functioning occur with elevated frequency in both older adults and patients with cancer. With the predicted increase in both of these populations in the coming decades, it is imperative to evaluate potential interventions that are designed to help older cancer patients compensate for the additive burden of this disease and its treatment on age-related taste and smell losses. OBJECTIVE: The purpose of the current study was to determine if providing instruction and products for flavor enhancement of foods to elderly cancer patients in addition to nutritional information would improve their nutritional status, and, by extension, functional and immune status as well as quality of life. DESIGN: One hundred and seven subjects enrolled in the study. Fifty-four subjects were in the experimental group that received flavor enhancement plus nutritional information; fifty-three control subjects received only nutritional information. Subjects were evaluated 1 month, 3 months, and 8 months after beginning chemotherapy. At every session, subjects completed taste and smell assessments as well as questionnaires related to nutritional status, activities of daily living, and quality of life. Blood samples were also obtained to determine immune parameters. RESULTS: At the eight-month time point, experimental subjects had better scores on the mini nutritional assessment (MNA) and the physical function assessment of the quality of life questionnaire. Also at eight months, self-reported taste and smell perception for experimental subjects was better than that of controls as well as better than at earlier time points. Tests that assessed quantity and quality of food intake, as well as a number of immune parameters declined over time and did not differ significantly between groups. CONCLUSION: The combination of flavor enhancement, chemosensory education, and nutritional information for elderly cancer patients improved their nutritional assessment on the MNA and physical function over time. On the whole, experimental subjects perceived themselves to be better functioning at eight months than did their control counterparts.

Nitric oxide: a key regulator of myeloid inflammatory cell apoptosis.

Apoptosis of inflammatory cells is a critical event in the resolution of inflammation, as failure to undergo this form of cell death leads to increased tissue damage and exacerbation of the inflammatory response. Many factors are able to influence the rate of apoptosis in neutrophils, eosinophils, monocytes and macrophages. Among these is the signalling molecule nitric oxide (NO), which possesses both anti- and proapoptotic properties, depending on the concentration and flux of NO, and also the source from which NO is derived. This review summarises the differential effects of NO on inflammatory cell apoptosis and outlines potential mechanisms that have been proposed to explain such actions.

The effect of an intralesional sustained-release formulation of interferon alfa-2b on basal cell carcinomas.

Intralesional interferon alfa-2b has been proven effective in the treatment of basal cell carcinomas. Because nine injections over a 3-week period have been necessary to produce clinically significant cure rates, a sustained-release protamine zinc chelate interferon formulation has been developed. In this study, 65 basal cell carcinomas were treated in one of two dosing schedules with intralesional sustained release interferon alfa-2b (10 million IU per injection). Thirty-three patients received a single injection and 32 patients received one injection per week for 3 weeks. At study week 16, 80% of evaluable tumors treated with three injections and 52% treated with one injection were cured histologically. Two patients discontinued injections because of side effects. A sustained-release protamine zinc preparation of interferon alfa-2b shows promise as a practical, effective, and cosmetically elegant treatment for basal cell carcinoma.

Treatment of cutaneous squamous cell carcinomas by intralesional interferon alfa-2b therapy.

BACKGROUND AND DESIGN: Intralesional recombinant interferon alfa-2b has been shown to be effective in the treatment of actinic keratoses and basal cell carcinomas. This open-label study was designed to evaluate the effectiveness and cosmetic result of this therapy on actinically induced, primary cutaneous squamous cell carcinomas. Thirty-six squamous cell carcinomas (28 invasive lesions and 8 in situ lesions) ranging in size from 0.5 to 2.0 cm in the longest dimension were treated with interferon alfa-2b 1.5 million units injected intralesionally three times per week for 3 weeks. Eighteen weeks following therapy, the treatment sites were excised and examined for histologic evidence of remaining tumor. RESULTS: Thirty-three (97.1%) of 34 evaluable lesions revealed an absence of squamous cell carcinoma histologically after therapy, although three biopsy specimens (8.8%) obtained after treatment showed actinic keratoses, for an overall complete response rate of 88.2%. The lesion not eliminated after treatment was an invasive squamous cell carcinoma. The investigators and patients independently judged 93.9% of cases to have a very good or excellent cosmetic result. Adverse reactions were limited to those influenzalike symptoms well recognized to occur with interferon therapy and these were well tolerated. Only one patient discontinued therapy due to side effects. CONCLUSIONS: This trial demonstrates that intralesional interferon is effective in the treatment of small sun-induced squamous cell carcinomas with well-tolerated side effects and a highly acceptable cosmetic result.

The gynecologist and cardiovascular disease: a window of opportunity for prevention.

OBJECTIVE: We present current concepts and assess the quality of information available for the prevention of cardiovascular disease in women. METHODS: This article reviews research bearing on the prevention of cardiovascular disease in women, with particular attention to modifiable risk factors. We describe the magnitude of the problem and assess the quality of the data with respect to the classic risk factors. The concept is emphasized that changes at menopause, states of endocrine aberration, and benefits and risks of hormone substitution and oral contraception must be understood in conjunction with all other potentially modifiable and nonmodifiable risk factors. CONCLUSIONS: Primary care physicians, especially obstetrician/gynecologists, have a pivotal role to play in the reduction of this disease. Behavior modification is the key to integrating prevention into the regular annual visit.

Matriarchal model for cardiovascular prevention.

Family patterns of cardiovascular risk behavior are well documented. Significant correlation exists between spouse-spouse, parent-child, and sibling-sibling for cholesterol, high- and low-density lipoprotein, diet, physical activity, and smoking. Family/environmental influences are important in how/if risk and/or preventive behavior is learned. The family matriarch commonly functions as gatekeeper, controlling eating behavior, access to health care, and other patterns. She often acts as menu planner, shopper, and preparer of meals for all family members. She provides information and verbal reinforcement about food and is a powerful model concerning dietary practices. In fact, the mother, as head of household in most single-parent families, may be the only adult model for many children. Because relevance and credibility are the most important characteristics of a behavioral model, parents (especially mothers) are strong models for observational learning by children. Risk factor information and risk reduction activities adopted by the matriarch can be generalized to the entire family if she learns the skills to act as a change agent. Initiation of this process of education and training the matriarch lies with primary care providers for women (Ob-Gyns see most women). By teaching risk reduction to the matriarch as a component of primary care, physician interaction can have a rippling effect.

Risk assessment for HIV infection: validation study of a computer-assisted preliminary screen.

Development has been undertaken for microcomputer software intended to assess individual risk for HIV infection by analyzing personal case histories pertinent to drug abuse, receptive blood transfusion, and sexual behavior. The software performs interactive confidential interviews of individuals desiring expert assistance when deciding whether to commit to an antibody test. In the first phase of a validation study, 87 subjects responded to the computer interview. For each subject, human immunodeficiency virus (HIV) antibody status was on clinical record. This sample included 70 subjects, 29 of whom were HIV seropositive, recruited from the clientele of an AIDS antibody testing and counseling facility. In this phase, the software accurately assessed 28 of 29 seropositives (96.6%) to be at risk for HIV. The second phase was based upon participation of an additional 74 subjects who were undergraduates at the University of Oklahoma. In this presumed low-risk sample, 55 members reported never having previously tested for HIV antibodies. Seven members (12.7%) of the untested group were declared at risk in the course of receiving confidential computer screen advice. Of these 7, there were 3 members (42.9%) who were motivated by the computer to voluntarily seek HIV antibody testing. Of the 7 declared at risk, 2 members (3.9%) were among the 51 seronegative subjects classified as heterosexuals without specific and identified risks. All Phase II subjects seeking follow-up antibody tests were found seronegative.

The advantages of aminolevulinic acid photodynamic therapy in dermatology.

Photodynamic therapy (PDT) is being increasingly employed in the detection and treatment of malignant and non-malignant disease. This local technique uses a photosensitizing drug activated by light to generate cell death via the production of reactive oxygen species. This review describes the fundamental processes behind PDT, focussing on the use of 5-aminolevulinic acid (ALA). ALA itself is not a photosensitizing drug, but administration of exogenous ALA induces the build-up of the natural endogenous photosensitizer protoporphyrin IX (PpIX). This form of PDT has proved promising for the treatment of a number of dermatological indications. An overview of these current and potential applications of ALA-based PDT is presented, with emphasis on the advantages of the technique that make it especially suitable for skin conditions and the problem areas on which future research should be focussed.

Critical tests and safety studies on trichlorfon as an antiparasitic agent in the horse.

Three series of critical tests were completed on a combined total of 46 horses to determine the efficacy of single doses of trichlorfon against bots, ascarids, pinworms, and large strongyles. Different formulations of trichlorfon were administered by tubing intragastrically, mixing with the daily grain ration, injecting intramuscularly, or pouring on the back at dose rates between 20 and 100 mg/kg. Administration by feeding tended to be more efficacious for removal of bots and less toxic to the horese than administration by stomach tube. In many of the tests, trichlorfon was given in the grain ration at the dose rate of 40 mg/kg of body weight, and the aggregate average removals of 2nd and 3rd instars of Gastrophilus intestinalis and Gasterophilus nasalis in the 3 series of tests were between 97 and 100%. Removal of Parascaris equorum was equally efficacious with both the intubation and the grain feeding methods of dosing, and at the dose rate of 40 mg/kg, the aggregate averages were 99 and 100% in the 3 series. Removal of Oxyuris equi was variable--aggregate averages were between 11 (1 infected horse in the initial series) and 96 (5 infected horses in the 3rd series) to 100% (7 infected horses in the 2nd series). Large strongyles, Strongylus vulgaris and Strongylus edentatus were almost completely refractory to the 40-mg/kg dose rate of trichlorfon. Dose rates of 40 mg/kg and less were generally well tolerated by the critical test horses. Higher dose rates (60 and 80 mg/kg) administered by stomach tube induced moderately severe to severe colic and diarrhea, whereas a dose of 80 mg/kg given in the feed resulted in only a transient softening of the feces. Likewise, 5 consecutive doses, 1 week between doses, of a bolus formulation given at the rate of 80 mg/kg to 4 horses were well tolerated. Clinical trials involving a total of 2,294 treatments of trichlorfon at dose rate of 35 to 40 mg/kg in pregnant and nonpregnant mares, stallions, suckling and weanling foals, yearlings, and horses in training on 38 farms in central Kentucky did not cause notable adverse clinical effects.

Effects of intravenous administration of formaldehyde on platelet and coagulation variables in healthy horses.

OBJECTIVES: To assess safety and determine effects of IV administration of formaldehyde on hemostatic variables in healthy horses. ANIMALS: 7 healthy adult horses. PROCEDURE: Clinical signs and results of CBC, serum biochemical analyses, and coagulation testing including template bleeding time (TBT) and activated clotting time (ACT) were compared in horses given a dose of 0.37% formaldehyde or lactated Ringer's solution (LRS), IV, in a 2-way crossover design. In a subsequent experiment, horses received an infusion of 0.74% formaldehyde or LRS. In another experiment, horses were treated with aspirin to impair platelet responses prior to infusion of formaldehyde or LRS. RESULTS: Significant differences were not detected in any variable measured between horses when given formaldehyde or any other treatment. Infusion of higher doses of formaldehyde resulted in adverse effects including muscle fasciculations, tachycardia, tachypnea, serous ocular and nasal discharge, agitation, and restlessness. CONCLUSIONS AND CLINICAL RELEVANCE: Intravenous infusion of formaldehyde at doses that do not induce adverse reactions did not have a detectable effect on measured hemostatic variables in healthy horses.

Cholecystitis and cholelithiasis.

Cholelithiasis and cholecystitis, with their complications, remain major health problems in the United States. At this time, cholecystectomy is the treatment of choice for all patients with symptomatic gallstones and those with acute cholecystitis, except those who are too ill to undergo surgery. Present therapeutic options may be summarized as follows: Asymptomatic patients and those with flatulence and dyspepsia who have gallstones should be observed. Those who have symptoms of biliary pain, gallstone-induced pancreatitis, or common duct stones should have corrective surgery. Those who refuse surgery or who aren't surgical candidates might be treated with dissolution therapy. Dissolution of gallstones with chemical agents and extracorporeal shock-wave lithotripsy show some promise. We need a better understanding of the etiology and formation of gallstones to address the disease from a preventive standpoint and reduce the incidence of cholelithiasis and cholecystitis, and their complications.

An unusual, structurally preserved ovule from the Permian of Antarctica.

Anatomically preserved ovules are described from silicified peat of Late Permian age collected from Skaar Ridge in the central Transantarctic Mountains, Antarctica. The small ovules are significant in possessing fleshy apical appendages and a funnel-shaped micropylar extension formed by the sarcotestal layer of the integument, by which they differ from all other Permian ovules described to date. The apical modifications may have functioned in pollination and/or seed dispersal. Similarity with the apical organization of earlier Paleozoic ovules is shown to be superficial, since the analogous structures are developmentally derived from different tissues. Although the ovules occur in rocks in which glossopterids are the only gymnosperms represented, there is insufficient evidence to assign them to a taxonomic group. These ovules are of particular importance because there are so few anatomically preserved gymnosperm reproductive structures known from the Permian and thus provide new data on the diversity of late Paleozoic gymnosperms.

Cuticles of Mariopteris occidentalis White nov. emend. from the Middle Pennsylvanian of Oklahoma (USA), and a new type of climber hook for mariopteroid pteridosperms.

Cuticles of Mariopteris occidentalis are described from the Desmoinesian (Middle Pennsylvanian) of Oklahoma (USA). This species, like other mariopteroids, had a vine- to liana-like growth habit and climbed with specialized climber hooks. However, M. occidentalis is different from other mariopteroids in having small recurved hooks on the abaxial surfaces of the pinna axes. The diagnosis for M. occidentalis White 1899 is emended based on additional macroscopical observations and data on the epidermal anatomy; a lectotype is designated. M. occidentalis is compared with Pseudomariopteris cordato-ovata from the Stephanian and Autunian of Europe and North America, a taxon which is considered very similar and may be related. Although the two taxa indeed display similarities, significant evidence for a closer relationship could not be found. Finally, some features, e.g. marginal water pits and the stomatal structure, are considered with regard to their palaeoautecological significance where they are interpreted as adaptations to special physiological requirements of a vine- to liana-like life form.

Stability and convergent validity of the Physical Activity Scale for the Elderly (PASE).

AIM: The purpose of this study was to assess the stability and convergent validity of the Physical Activity Scale for the Elderly (PASE) among rural, community dwelling elderly persons using Computer Science and Applications, Inc. Actigraph Monitors (Actigraph) as the direct criterion measure. EXPERIMENTAL DESIGN: a correlational design was employed. SETTING: rural community in the United States. PARTICIPANTS: 56 subjects (age=75.7+/-7.9 years) who were living independently and volunteered to participate in the study. MEASURES: subjects wore an Actigraph monitor during all waking hours for 7 consecutive days. At the conclusion of the 7 days, each subject met with a trained interviewer to complete the PASE questionnaire. Three days later the subjects met with the same interviewer to complete the PASE a 2nd time recalling their physical activity for the same 7-day period. RESULTS: Actigraph data indicated that subjects averaged 168.1+/-76.3 counts x minute(-1) during the 7-day period. A high intraclass correlation coefficient (r=0.91) was calculated between the 1st interview total PASE score (115.97+/-59.91) and the 2nd interview total PASE score (115.71+/-50.97). In addition, there was a statistically significant Spearman correlation coefficient of 0.43 (p<0.01) between Actigraph mean counts x minute(-1) and 1st interview total PASE scores. CONCLUSION: In this rural elderly sample, the PASE was a stable instrument with validity indices similar to those previously reported in younger, more active, populations.

Permian polar forests: deciduousness and environmental variation.

Forests are expected to expand into northern polar latitudes in the next century. However, the impact of forests at high latitudes on climate and terrestrial biogeochemical cycling is poorly understood because such forests cannot be studied in the modern. This study presents forestry and geochemical analyses of three in situ fossil forests from Late Permian strata of Antarctica, which grew at polar latitudes. Stem size measurements and stump spacing measurements indicate significant differences in forest density and canopy structure that are related to the local depositional setting. For forests closest to fluvial systems, tree density appears to decrease as the forests mature, which is the opposite trend of self-thinning observed in modern forests. We speculate that a combination of tree mortality and high disturbance created low-density mature forests without understory vegetation near Late Permian river systems. Stable carbon isotopes measured from permineralized wood in these forests demonstrate two important points: (i) recently developed techniques of high-resolution carbon isotope studies of wood and mummified wood can be applied to permineralized wood, for which much of the original organic matter has been lost and (ii) that the fossil trees maintained a deciduous habit at polar latitudes during the Late Permian. The combination of paleobotanical, sedimentologic, and paleoforestry techniques provides an unrivaled examination of the function of polar forests in deep time; and the carbon isotope geochemistry supplements this work with subannual records of carbon fixation that allows for the quantitative analysis of deciduous versus evergreen habits and environmental parameters, for example, relative humidity.