Climate-change-driven accelerated sea-level rise detected in the altimeter era.

Using a 25-y time series of precision satellite altimeter data from TOPEX/Poseidon, Jason-1, Jason-2, and Jason-3, we estimate the climate-change-driven acceleration of global mean sea level over the last 25 y to be 0.084 ± 0.025 mm/y2 Coupled with the average climate-change-driven rate of sea level rise over these same 25 y of 2.9 mm/y, simple extrapolation of the quadratic implies global mean sea level could rise 65 ± 12 cm by 2100 compared with 2005, roughly in agreement with the Intergovernmental Panel on Climate Change (IPCC) 5th Assessment Report (AR5) model projections.

The effect of temperature on the autofluorescence of scattering and non-scattering tissue.

BACKGROUND AND OBJECTIVES: With the increasing use of fluorescence in medical applications, a comprehensive understanding of the effect of temperature on tissue autofluorescence is essential. The purpose of this study is to explore the effect of temperature on the fluorescence of porcine cornea and rat skin and determine the relative contributions of irreversible changes in optical properties and in fluorescence yield. STUDY DESIGN/MATERIALS AND METHODS: Fluorescence, diffuse reflectance, and temperature measurements were acquired from excised porcine cornea and rat skin over a temperature range of 0-80 °C. A dual excitation system was used with a 337 nm pulsed nitrogen laser for the fluorescence and a white light source for the diffuse reflectance measurements. A thermal camera measured tissue temperature. Optical property changes were inferred from diffuse reflectance measurements. The reversibility of the change in fluorescence was examined by acquiring measurements while the tissue sample cooled from the highest induced temperature to room temperature. RESULTS: The fluorescence intensity decreased with increasing tissue temperature. This fluorescence change was reversible when the tissue was heated to a temperature of 45 °C, but irreversible when heated to a temperature of 80 °C. CONCLUSION: Auto-fluorescence intensity dependence on temperature appears to be a combination of temperature-induced optical property changes and reduced fluorescence quantum yield due to changes in collagen structure. Temperature-induced changes in measured fluorescence must be taken into consideration in applications where fluorescence is used to diagnose disease or guide therapy.

Offspring born to ewes fed high salt during pregnancy have altered responses to oral salt loads.

Prenatal growth is sensitive to the direct and indirect effects of maternal dietary intake; manipulation can lead to behavioural and physiological changes of the offspring later in life. Here, we report on three aspects of how a high-salt diet during pregnancy (conception to parturition) may affect the offspring's response to high oral salt loads: (i) dietary preferences for salt; (ii) response to salt and water balance and aldosterone and arginine vasopressin (AVP) concentrations after an oral salt challenge; (iii) concentrations of insulin and leptin after an oral salt challenge. We used two groups of lambs born to ewes fed either a high-salt (13% NaCl) diet during pregnancy (S lambs; n = 12) or control animals born to ewes fed a conventional (0.5% NaCl) diet during pregnancy (C lambs; n = 12). Lambs were subjected to short- (5 min) and long-term (24 h) preference tests for a high-salt (13% NaCl) or control diet, and the response to an oral challenge with either water or 25% NaCl solution were also carried out. Weaned lambs born to ewes fed high salt during pregnancy did not differ in their preference for dietary salt, but they did differ in their physiological responses to an oral salt challenge. Results indicate that these differences reflect an alteration in the regulation of water and salt balance as the metabolic hormones, insulin and leptin, were not affected. During the first 2 h after a single salt dose, S lambs had a 25% lower water intake compared to the C lambs. S lambs had, on average, a 13% lower AVP concentration than the C lambs (P = 0.014). The plasma concentration of aldosterone was higher in the S lambs than in the C lambs (P = 0.013). Results suggest that lambs born to ewes that ingest high amounts of salt during pregnancy are programmed to have an altered thirst threshold, and blunted response in aldosterone to oral salt loads.

The effect of grazing saltbush with a barley supplement on the carcass and eating quality of sheepmeat.

The carcass and eating quality of sheep grazing a saltbush dominant saline pasture system or on a 'control' dry pasture, stubble plot both supplemented with barley for 14 weeks was investigated (Experiment 1, 50 (2×25) 6 month merino lamb wethers and Experiment 2, 50 (2×25) 18 month old merino hogget wethers). Treatment had no significant effect on eating quality attributes (P>0.05). Saltbush grazed sheep in both experiments had a significantly (P<0.01) lower carcass fat and significantly higher lean (P<0.01) content than the control grazed sheep. This is a positive finding as fat denudation is a significant cost to processors. The long term consumption of saltbush and barley prior to slaughter did increase muscle fluid content (P<0.05) but did not result in a decreased carcass weight loss at slaughter due to confounding changes in body composition. Grazing saltbush resulted in increased urine weight (P<0.001) and decreased urine concentration (P<0.05) at slaughter indicating an improved hydration status at slaughter. However both experiments demonstrated sub-optimal liveweight gains indicating that saltbush with a barley supplement can still be effectively used as a maintenance ration without compromising carcass and eating quality.

Reproductive capacity of Merino ewes fed a high-salt diet.

An option to increase the productivity of saline land is to graze sheep on salt-tolerant plants, which, during the summer/autumn period, can contain 20% to 25% of their dry matter as salt. This study assessed the impact of coping with high dietary salt loads on the reproductive performance of grazing ewes. From the time of artificial insemination until parturition, 2-year-old maiden Merino ewes were fed either a high-salt diet (NaCl 13% of dry matter) or control diet (NaCl 0.5% of dry matter). Pregnancy rates, lamb birth weights, milk composition and the plasma concentrations of hormones related to salt and water balance, and energy metabolism were measured. Leptin and insulin concentrations were lower (1.4 ± 0.09 v. 1.5 ± 0.12 ng/ml; (P < 0.05) and 7.2 ± 0.55 v. 8.2 ± 0.83 ng/ml; P < 0.02) in response to high-salt ingestion as was aldosterone concentration (27 ± 2.7 v. 49 ± 5.4 pg/ml; P < 0.05), presumably to achieve salt and water homeostasis. Arginine vasopressin concentration was not significantly affected by the diets, but plasma concentration of T3 differed during gestation (P < 0.02), resulting in lower concentrations in the high-salt group in the first third of gestation (1.2 ± 0.18 v. 1.3 ± 0.14 pmol/ml) and higher concentrations in the final third of gestation (0.8 ± 0.16 v. 0.6 ± 0.06 pmol/ml). T4 concentration was lower in ewes ingesting high salt for the first two-thirds of pregnancy (162 ± 8.6 v. 212 ± 13 ng/ml; P < 0.001). No substantial effects of high salt ingestion on pregnancy rates, lamb birth weights or milk composition were detected.

The effect of ingesting a saltbush and barley ration on the carcass and eating quality of sheepmeat.

Forage halophytes such as saltbush (Atriplex spp.) are widely used to revegetate Australian saline land and can provide a medium-quality fodder source. An animal house experiment was conducted to investigate differences in the carcass and eating quality of sheep ingesting saltbush from saline land in combination with a barley supplement. Twenty-six merino hoggets (two groups of 13) were fed either a 60 : 40 dried saltbush (Atriplex nummularia): barley (S + B) ration or a 33 : 25 : 42 lupins : barley : oaten hay ration (C) for 10 weeks prior to commercial slaughter. After 10 weeks, all sheep were commercially slaughtered and a single loin (from 12th rib to chump) collected from each animal for taste-panel analysis. Carcass weight, total tissue depth over the 12th rib 110 mm from the midline (GR fat depth), ultimate pH and colour were determined and X-ray bone densitometry used to estimate the fat content of the carcass. Blood samples were taken to assess the hormonal response to ingesting these diets and fatty acid profiles of the subcutaneous and intramuscular fat were determined. Both groups grew at the same rate (62 g/day) and had similar hot carcass weights (P > 0.01) (17.2 ± 0.3 kg for S + B and 17.9 ± 0.3 kg for C). However, these live weights may not be high enough to be commercially viable such that saltbush and barley may only be suitable as a maintenance feed. The S + B-fed sheep had a significantly (P = 0.055) lower fat and higher lean content (P < 0.05) than the C group. This is a positive finding as fat denudation is a significant cost to processors and farmers can produce sheep that are depositing less fat or more lean per unit of live-weight gain. The decreased fat and increased lean content were attributed to the higher protein : energy ratio available for production and lower circulating insulin and higher growth hormone of the S + B-fed sheep. The lower body-fat content and lower metabolisable energy and digestible organic matter intake did correlate with the sheep fed the S + B diet, having a significantly lower percentage of unsaturated fat and equal levels of saturated fat than the C treatment. Diet had no effect on the ultimate pH or colour of the meat. Treatment had no significant effect on any of the eating-quality attributes (P > 0.1). The drying of the saltbush, the shorter length of the experimental period and the low carcass fat content were believed to have contributed to this result. Further field experiments are needed to clarify the benefits to carcass and eating quality of ingesting saltbush.

Transsulfuration, protein synthesis rate and follicle mRNA in the skin of young Merino lambs in response to infusions of methionine and serine.

Methionine (Met) is usually the first limiting amino acid for sheep and supplements of Met may increase production of wool and meat. The wool response may be due to an increased supply of cysteine (Cys) from transsulfuration (TS) of Met. Met is catabolized through homocysteine to form Cys when the S from Met is transferred to serine (Ser). We hypothesized that providing additional Met would create a deficiency of Ser and that by simultaneously providing Met and Ser, TS and wool growth could be increased more than by providing Met alone. The effects of i.v. infusions of Met and Ser to young Merino lambs on TS, fractional synthesis rate (FSR) of protein in skin, follicle mRNA and wool growth were examined. Following 4 d of constant i.v. infusion of 3 g Met/d, or 10 g Ser/d or both, the isotope tracers: L-[3-(13)C]Cys, L-[ring-d5]phenylalanine (Phe) and L-[2,3,3-d3]Ser were infused over 8 h to allow for measurements of irreversible loss rate (ILR), and TS in whole body and skin. Skin biopsies were taken for measurement of FSR. Wool growth rate was measured using autoradiography. An infusion of Met significantly (P < 0.05) improved wool growth rate and increased skin FSR, Cys supply from TS and enhanced levels of follicle mRNA (from the K2.10 intermediate filament gene and three gene families encoding keratin associated proteins KAP1, KAP4 and KAP12). The extra Met lowered Ser ILR. The infusion of Ser doubled Ser ILR in the body and increased skin FSR calculated using the Cys tracer in plasma (P < 0.05). However, there were no significant (P > 0.05) changes in TS, skin FSR calculated using the Phe and Ser tracers, follicle mRNA or wool growth rate as a result of Ser infusion. While there were trends towards increased TS and FSR with Ser infusion, the overall lack of significant changes indicates a high capacity for the de novo synthesis of Ser.

Seasonality and factors associated with cryptosporidiosis among individuals with HIV infection.

The seasonality and factors associated with Cryptosporidium infection were assessed in a cohort of HIV-infected patients in Los Angeles County to better define the epidemiology of cryptosporidiosis among individuals with HIV. Data were analysed from a cohort of 4247 patients > or = 13 years of age with HIV infection enrolled from four outpatient facilities in Los Angeles, 1990-6. Cryptosporidiosis was diagnosed in 120 (2.8%) patients. Among the 1296 individuals with complete follow-up until death, cryptosporidiosis occurred in 69 (5.3%). The seasonal rate of cryptosporidiosis showed a modest bimodal trend with the highest rates occurring in March-May and September-October. There was no difference in the rate of cryptosporidiosis for the periods of heaviest rainfall (December-March) and low rainfall (April-November). Infection rates were higher among males (1.59 per 100 person-years) than females (0.92) and lower in blacks (0.98) than other racial/ethnic groups (1.80). A significant trend of decreasing cryptosporidiosis was observed with increasing age, with the highest rate (2.34) in the 13-34 year age group. A strong association between cryptosporidiosis and CD4+ count was noted. These data suggest that cryptosporidiosis among HIV-infected individuals in Los Angeles County exhibits a modest spring and fall seasonality. This pattern of occurrence of cryptosporidiosis appears temporally unrelated to local rainfall patterns. Our findings suggest that HIV-infected men, individuals in younger age groups and those with CD4+ lymphocyte counts < 100 x 10(6)/l are at increased risk of cryptosporidiosis. Blacks with HIV infection appear less likely than other racial/ethnic groups to be diagnosed with Cryptosporidium infection. These results may provide insight into possible routes of transmission and sources of cryptosporidiosis infection in individuals with HIV.

Liposphere local anesthetic timed-release for perineural site application.

PURPOSE: This investigation determines the drug delivery capacity of Lipospheres, which are drug-containing solid-filled vesicles made of triglyceride with a phospholipid outer covering, to release local anesthetic in vitro and to produce sustained peripheral nerve block in vivo. METHODS: The local anesthetic, bupivacaine, was loaded into Lipospheres in several dosage forms, characterized, and measured for in vitro release. In rats, Lipospheres were administered into a large space between muscle layers surrounding the sciatic nerve to assess sensory and motor block in vivo. RESULTS: The particle size of Lipospheres was determined to be between 5 and 15 microm, with over 90% surface phospholopid. Lipospheres released bupivacaine over two days under ideal sink conditions. Liposphere nerve application produced dose-dependent and reversible block. Indeed, sustained local anesthetic block (SLAB) was observed for 1-3 days in various in vivo tests: a) Hind paw withdrawal latency to noxious heat was increased over 50% for 96 hr period after application of 3.6% or 5.6% bupivacaine-Lipospheres. The 3.6% and 5.6% doses were estimated to release bupivacaine at 200 and 311 microg drug/ hr, respectively, based on release spanning 72 hr. Application of 1.6% bupivacaine-Lipospheres increased withdraw latency 25-250% but for only a 24 hr duration; b) Similarly, vocalization threshold to hind paw stimulation was increased 25-50% for 72 hr following application of 3.6% bupivacaine-Lipospheres; c) Finally, sensory blockade outlasted or equaled corresponding motor block duration for all Liposphere drug dosages. CONCLUSIONS: Liposphere delivery of local anesthetic drugs may be well suited for site-specific pharmacotherapy of neural tissue to produce SLAB. Dose-dependent effects in duration of action may include lipophilic tissue storage.

The influence of live weight, live-weight change and diet on protein synthesis in the skin and skeletal muscle in young Merino sheep.

Wool growth is derived directly from protein synthesis in the skin of sheep, and is affected by the nutritional status of the animals. The present experiment examined both protein synthesis in the skin and muscle and wool growth in Merino lambs differing in live weight, intake and dietary protein source. The experiment was a 2(3) factorial design: twenty-four 5-month-old lambs initially weighing 33 kg (heavy) or 25 kg (light) were fed on a hay-based diet with either lupin seed or rapeseed meal as the major protein sources to maintain live weight (M) for 56 d, or were fed at 0.6 M for 28 d (period 1) followed by 28 d at 1.6 M (period 2). Fractional protein synthesis rates (FSR, % per d) in the skin and the m. longissimus dorsi on days 4 and 24 of period 1 and day 4 of period 2 were measured by means of a flooding dose of L-[ring-d5]phenylalanine, and wool growth on a skin patch over period 1 was also measured. The FSR ranged from 13.2 to 20.2% per d in the skin, higher than reported for other breeds, and 1.53-3.07% per d in the muscle. Sheep on the low intake (0.6 M) had significant reductions in FSR, protein content (g), protein synthesis (g/d) in the skin, and wool growth (g/d). The heavy lambs had similar FSR to the light lambs, but had a higher skin protein content and total protein synthesis per unit of skin area (100 cm2) and, therefore, grew more wool. The rapeseed-meal diet increased FSR and wool growth only in the light lambs over the short term. The protein deposited in wool over period 1 was 0.185 of the total protein synthesis in the skin, regardless of live weight, intake or diet, a result similar to other breeds. With the changes in dietary intake, protein synthesis in the skin and muscle responded differentially, with nutrient partitioning at sub-maintenance in favour of wool growth but at supra-maintenance, following a nutrient restriction, in favour of weight gain in young growing sheep.

Cloning and expression of cystolic phospholipase A2 (cPLA2) and a naturally occurring variant. Phosphorylation of Ser505 of recombinant cPLA2 by p42 mitogen-activated protein kinase results in an increase in specific activity.

Full-length cytosolic phospholipase A2 (cPLA2) was cloned from U937 cells and polymorphonuclear leukocytes (PMNLs) while a naturally occurring variant of cPLA2, which lacks residues Val473-Ala749 but has a C-terminal extension of ILMNLSEYMLWMSKVKRFM (DcPLA2) was cloned from PMNLs and mononuclear leukocytes. We were unable to clone DcPLA2 from U937 cells. When cPLA2 and DcPLA2 were expressed in insect cells, both proteins were detected in cell lysates by SDS/PAGE as single bands of apparent molecular masses 100 kDa and 57 kDa, respectively. Full-length cPLA2 was phosphorylated stoichiometrically by p42 mitogen-activated protein (MAP) kinase in vitro at a similar rate to other physiological substrates of this protein kinase and the major site of phosphorylation was identified by amino acid sequencing as Ser505. [32P]Ser(P)505 in cPLA2 was only dephosphorylated at a slow rate by mammalian tissue homogenates. Protein phosphatases 2A, 2B and 2C all contributed significantly to the overall dephosphorylation of cPLA2. The phosphorylation of cPLA2 by p42 MAP kinase correlated with an approximately 1.5-fold increase in specific enzyme activity which was reversed by dephosphorylation.

The research career interests of graduating medical students.

In this baseline study, the authors analyze in detail many of the factors that influenced the research career intentions of the 1994 U.S. graduates of MD-only programs. Studies of the research interests of the nation's medical school graduates are important because MD-PhD programs do not produce sufficient numbers of physician-scientists, and the remainder must come from the regular population of medical graduates. Data on school characteristics and medical students' demographics, research career intentions, and educational experiences were derived from the AAMC's Institutional Profile System (IPS), Student Application and Information Management System (SAIMS), Matriculating Student Questionnaire (MSQ), and Medical School Graduation Questionnaire (GQ). The 1994 GQ was used as the index instrument to make the correlations reported in this article. A number of findings emerged concerning the 1994 graduates. A greater percentage of these students who began medical school with strong research career intentions and maintained these intentions had entered private medical schools. The lower rate of research interest amongst the students enrolled in public medical schools was compounded by the significantly greater loss of earlier research intentions of those in public schools compared with those in private schools.(ABSTRACT TRUNCATED AT 250 WORDS)

The properties of a cloned human high-molecular-mass cytosolic phospholipase A2 investigated using a continuous fluorescence displacement assay: evidence for enzyme clustering on phospholipid vesicles.

The 85 kDa human cytosolic phospholipase A2 has been cloned and expressed in insect Sf21 cells. The pure enzyme has been investigated using a fluorescence displacement assay that provides a continuous record of phospholipid hydrolysis [Wilton (1990) Biochem. J. 266, 435-439]. The unusual kinetic properties of this enzyme, previously described using radioactive assays, were readily demonstrated using the continuous fluorescence assay and were examined in detail. It is proposed that the enzyme clusters on the surface of a fixed number of substrate vesicles during the initial stages of catalysis and that the characteristic burst phase of hydrolysis represents the hydrolysis of these vesicles. This clustering produced a molar ratio of total phospholipid substrate to enzyme of about 450:1 at vesicle saturation with enzyme. Under limiting substrate conditions, the lower secondary rate that is observed results eventually in almost complete hydrolysis of the phospholipid; this was confirmed using radioactive substrate. Evidence is presented that during the initial burst phase, equivalent to hydrolysis of the outer monolayer of the vesicle, the enzyme remains tightly bound but is released as the reaction proceeds towards complete hydrolysis of the phospholipid substrate. In the presence of excess substrate, about 370 mol of fatty acid are released per mol of enzyme during the burst phase and it is calculated that this value also approximates to hydrolysis of the outer monolayer of the vesicle. It is proposed that the formation of a stable enzyme-vesicle complex during the burst phase of phospholipid hydrolysis may be due, at least in part, to protein-protein interactions between adjacent enzyme molecules in order to account for the clustering phenomenon.

Intracerebral administration of antisense oligodeoxynucleotides to GAD65 and GAD67 mRNAs modulate reproductive behavior in the female rat.

Increased GABA activity in the medial hypothalamus (HYP) and midbrain central gray (MCG), but not the preoptic area (POA), facilitates sexual receptivity in the female rat [40]. In the current experiments, ovariectomized females were chronically treated with estrogen (via silastic capsules) to maintain a continuously high level of lordosis response. Administration of crystalline antisense oligodeoxynucleotide to the GABA synthetic enzyme, GAD67, into the HYP and MCG significantly and reversibly reduced lordosis response for 1-2 days, but did not inhibit lordosis when administered into the POA. Administration of a control oligonucleotide, consisting of the same nucleotide bases but in a scrambled sequence, did not significantly modulate behavior when infused into any brain areas. When oligodeoxynucleotide antisense to GAD67 was suspended in oil and then infused into the HYP or MCG it was more effective and resulted in less inter-animal variability. Subsequent experiments involving infusions into the MCG compared the effectiveness of antisense oligonucleotides to the two different forms of GAD, known as GAD65 and GAD67. Oligodeoxynucleotides antisense to the mRNA for either gene were effective at reducing lordosis behavior but with a different time course. Oligonucleotide antisense to GAD67 significantly reduced behavior within 24 h of infusion and there was full recovery by 4 days post-infusion. GAD65 antisense oligonucleotide did not significantly reduce behavior until 48 h post infusion and animals did not fully recover to pretest levels of lordosis until 5 days post-infusion. When antisense oligonucleotide for the two genes was administered simultaneously, the inhibition of lordosis was maximal at 24 h and stayed depressed for 4 days. There did not appear to be an additive effect of the two different antisense oligonucleotides when administered together. Tissue GABA levels in HYP and MCG of individual rats assayed by HPLC were no longer correlated with lordosis score after antisense oligonucleotide infusion but were after infusions of scrambled control oligos. Immunoblotting for the two forms of GAD revealed that GAD67 antisense oligonucleotide infusion led to significant decreases in both GAD67 and GAD65 protein levels as compared to infusions of scrambled control oligo. In addition, the levels of a neuronal marker, neuron-specific enolase, also decreased (although nonsignificantly) suggesting either a temporary shutdown of protein synthesis or a degeneration of GABAergic neurons after GAD67 antisense oligonucleotide infusion.

Sustained local anesthetic release from bioerodible polymer matrices: a potential method for prolonged regional anesthesia.

Polyanhydride polymer matrices have been used successfully for sustained release of a number of drugs in vitro and in vivo. Dibucaine free base, dibucaine HCl, and bupivacaine HCl were incorporated into polymer matrices with copolymer 1,3-bis(p-carboxyphenoxy)propane-sebacic acid anhydride (1:4). Drug release was measured in vitro following incubation of the drug-polymer matrices in phosphate buffered solution, pH 7.4, at 37 degrees C, to approximate in vivo conditions. Local anesthetics were released in a sustained manner yielding 90% cumulative drug release over periods ranging from 3 to 14 days. The kinetics of release varied with both the choice of local anesthetic and the method of drug incorporation into the matrix (hot melt versus compression molding). Polymer local anesthetic matrix devices (PLAM), loaded by hot melt incorporation with 20% bupivacaine, were implanted in vivo adjacent to the sciatic nerve in three rats. Reversible neural blockade was observed for 4 days in all animals. Polymer implants without local anesthetic showed no neural blockade. This technology could lead to methods of prolonged blockade of peripheral nerves or of sympathetic ganglia, which may be utilized for the management of postoperative pain, sympathetically maintained pain, or certain forms of chronic pain.