Palaeoclimate evidence of vulnerable permafrost during times of low sea ice.

Climate change in the Arctic is occurring rapidly, and projections suggest the complete loss of summer sea ice by the middle of this century1. The sensitivity of permanently frozen ground (permafrost) in the Northern Hemisphere to warming is less clear, and its long-term trends are harder to monitor than those of sea ice. Here we use palaeoclimate data to show that Siberian permafrost is robust to warming when Arctic sea ice is present, but vulnerable when it is absent. Uranium-lead chronology of carbonate deposits (speleothems) in a Siberian cave located at the southern edge of continuous permafrost reveals periods in which the overlying ground was not permanently frozen. The speleothem record starts 1.5 million years ago (Ma), a time when greater equator-to-pole heat transport led to a warmer Northern Hemisphere2. The growth of the speleothems indicates that permafrost at the cave site was absent at that time, becoming more frequent from about 1.35 Ma, as the Northern Hemisphere cooled, and permanent after about 0.4 Ma. This history mirrors that of year-round sea ice in the Arctic Ocean, which was largely absent before about 0.4 Ma (ref. 3), but continuously present since that date. The robustness of permafrost when sea ice is present, as well as the increased permafrost vulnerability when sea ice is absent, can be explained by changes in both heat and moisture transport. Reduced sea ice may contribute to warming of Arctic air4-6, which can lead to warming far inland7. Open Arctic waters also increase the source of moisture and increase autumn snowfall over Siberia, insulating the ground from low winter temperatures8-10. These processes explain the relationship between an ice-free Arctic and permafrost thawing before 0.4 Ma. If these processes continue during modern climate change, future loss of summer Arctic sea ice will accelerate the thawing of Siberian permafrost.

An agenda for research and action toward diverse and just futures for life on Earth.

Decades of research and policy interventions on biodiversity have insufficiently addressed the dual issues of biodiversity degradation and social justice. New approaches are therefore needed. We devised a research and action agenda that calls for a collective task of revisiting biodiversity toward the goal of sustaining diverse and just futures for life on Earth. Revisiting biodiversity involves critically reflecting on past and present research, policy, and practice concerning biodiversity to inspire creative thinking about the future. The agenda was developed through a 2-year dialogue process that involved close to 300 experts from diverse disciplines and locations. This process was informed by social science insights that show biodiversity research and action is underpinned by choices about how problems are conceptualized. Recognizing knowledge, action, and ethics as inseparable, we synthesized a set of principles that help navigate the task of revisiting biodiversity. The agenda articulates 4 thematic areas for future research. First, researchers need to revisit biodiversity narratives by challenging conceptualizations that exclude diversity and entrench the separation of humans, cultures, economies, and societies from nature. Second, researchers should focus on the relationships between the Anthropocene, biodiversity, and culture by considering humanity and biodiversity as tied together in specific contexts. Third, researchers should focus on nature and economies by better accounting for the interacting structures of economic and financial systems as core drivers of biodiversity loss. Finally, researchers should enable transformative biodiversity research and action by reconfiguring relationships between human and nonhuman communities in and through science, policy, and practice. Revisiting biodiversity necessitates a renewed focus on dialogue among biodiversity communities and beyond that critically reflects on the past to channel research and action toward fostering just and diverse futures for human and nonhuman life on Earth.

Una Agenda para la Investigación y la Acción hacia un Futuro Diverso y Justo para la Vida sobre la Tierra Resumen Las décadas de investigación e intervenciones políticas sobre la biodiversidad han tratado significativamente los temas de la degradación de la biodiversidad y la justicia social. Debido a esto, se requieren nuevas estrategias. Diseñamos una agenda de investigación y acción que llama a la labor colectiva de revisar la biodiversidad hacia el objetivo de sustentar un futuro diverso y justo para la vida sobre la Tierra. Cuando se revisa la biodiversidad, se requiere de una reflexión crítica sobre las investigaciones, políticas y prácticas presentes y pasadas sobre la biodiversidad para inspirar un pensamiento creativo acerca del futuro. Desarrollamos la agenda por medio de un proceso de diálogo de dos años que involucró a casi 300 expertos de diversas disciplinas y localidades. Este proceso estuvo orientado por el conocimiento de las ciencias sociales que muestra cómo la investigación y la acción para la biodiversidad están sostenidas por las opciones de cómo están conceptualizados los problemas. Reconocimos al conocimiento, la acción y la ética como inseparables y sintetizamos un conjunto de principios que ayuda a navegar la labor de revisar la biodiversidad. La agenda articula cuatro áreas temáticas para la investigación en el futuro. Primero, los investigadores necesitan revisar las narrativas de la biodiversidad mediante el cuestionamiento de las conceptualizaciones que excluyen a la diversidad y consolidan la separación entre humanos, culturas, economías y sociedades y la naturaleza. Segundo, los investigadores deberían enfocarse en las relaciones entre el antropoceno, la biodiversidad y la cultura al considerar a la humanidad y la biodiversidad como interconectadas en contextos específicos. Tercero, los investigadores deberían enfocarse en la naturaleza y las economías al tener en mejor cuenta la interacción de las estructuras de los sistemas económico y financiero como conductores nucleares de la pérdida de la biodiversidad. Finalmente, los investigadores deberían permitir la investigación y acción transformadoras de la biodiversidad al reconfigurar las relaciones entre las comunidades humanas y no humanas dentro y a través de la ciencia, la política y la práctica. La revisión de la biodiversidad necesita de un enfoque renovado sobre el diálogo entre las comunidades de la biodiversidad y más allá, que reflexione críticamente sobre el pasado para canalizar a la investigación y acción hacia el fomento del futuro justo y diverso para la vida humana y no humana sobre la Tierra.

Putting the public (back) into public health: leadership, evidence and action.

There is a strong evidence-based rationale for community capacity building and community empowerment as part of a strategic response to reduce health inequalities. Within the current UK policy context, there are calls for increased public engagement in prevention and local decision-making in order to give people greater control over the conditions that determine health. With reference to the challenges and opportunities within the English public health system, this essay seeks to open debate about what is required to mainstream community-centred approaches and ensure that the public is central to public health. The essay sets out the case for a reorientation of public health practice in order to build impactful action with communities at scale leading to a reduction in the health gap. National frameworks that support local practice are described. Four areas of challenge that could potentially drive an implementation gap are discussed: (i) achieving integration and scale, (ii) effective community mobilization, (iii) evidencing impact and (iv) achieving a shift in power. The essay concludes with a call to action for developing a contemporary public health practice that is rooted in communities and offers local leadership to strengthen local assets, increase community control and reduce health inequalities.

Type VI secretion requires a dynamic contractile phage tail-like structure.

Type VI secretion systems are bacterial virulence-associated nanomachines composed of proteins that are evolutionarily related to components of bacteriophage tails. Here we show that protein secretion by the type VI secretion system of Vibrio cholerae requires the action of a dynamic intracellular tubular structure that is structurally and functionally homologous to contractile phage tail sheath. Time-lapse fluorescence light microscopy reveals that sheaths of the type VI secretion system cycle between assembly, quick contraction, disassembly and re-assembly. Whole-cell electron cryotomography further shows that the sheaths appear as long tubular structures in either extended or contracted conformations that are connected to the inner membrane by a distinct basal structure. These data support a model in which the contraction of the type VI secretion system sheath provides the energy needed to translocate proteins out of effector cells and into adjacent target cells.

Ulcerative cellulitis of the arm: a case of primary cutaneous cryptococcosis.

Cutaneous cryptococcosis is usually secondary to the hematogenous dissemination of pulmonary or meningeal Cryptococcus neoformans. Primary cutaneous cryptococcosis (PCC) is a rare form of the infection, typically caused by direct inoculation from trauma to the skin [1]. Most cases of PCC present as a localized cellulitis, abscess, nodule, or ulceration. Herein, we present a case of a rapidly spreading cellulitis characterized by bullae and ulceration, caused by direct inoculation from a fall.

Changes in rumen microbiota composition and in situ degradation kinetics during the dry period and early lactation as affected by rate of increase of concentrate allowance.

Changes in rumen microbiota and in situ degradation kinetics were studied in 12 rumen-cannulated Holstein Friesian dairy cows during the dry period and early lactation. The effect of a rapid (RAP) or gradual (GRAD) postpartum (pp) rate of increase of concentrate allowance was also investigated. Cows were fed for ad libitum intake and had free access to a mixed ration consisting of chopped wheat straw (dry period only), grass silage, corn silage, and soybean meal. Treatment consisted of either a rapid (1.0 kg of dry matter/d; n = 6) or gradual (0.25 kg of dry matter/d; n = 6) increase of concentrate allowance (up to 10.9 kg of dry matter/d), starting at 4 d pp. In whole rumen contents, bacterial community composition was assessed using samples from 50, 30, and 10 d antepartum (ap), and 3, 9, 16, 30, 44, 60, and 80 d pp, and protozoal and archaeal community composition using samples from 10 d ap, and 16 and 44 d pp. Intake of fermentable organic matter, starch, and sugar was temporarily greater in RAP than GRAD at 16 d pp. Bacterial community richness was higher during the dry period than during the lactation. A rapid increase in concentrate allowance decreased bacterial community richness at 9 and 16 d pp compared with a gradual increase in concentrate allowance, whereas from 30 d pp onward richness of RAP and GRAD was similar. In general, the relative abundances of Bacteroidales and Aeromonadales were greater, and those of Clostridiales, Fibrobacterales, and Spirochaetales were smaller, during the lactation compared with the dry period. An interaction between treatment and sampling day was observed for some bacterial community members, and most of the protozoal and archaeal community members. Transition to lactation increased the relative abundance of Epidinium and Entodinium, but reduced the relative abundance of Ostracodinium. Archaea from genus Methanobrevibacter dominated during both the dry period and lactation. However, during lactation the abundance of the methylotrophic Methanomassiliicoccaceae and Methanosphaera increased. The in situ degradation of organic matter, neutral detergent fiber, starch, and crude protein was neither affected by treatment nor by transition from the dry period to lactation. Results show that the composition of the rumen microbiota can change quickly from the dry period to the lactation period, in particular with a rapid increase in fermentable substrate supply postpartum, but this was not associated with changes in rumen degradation kinetics.

First Report of Anthracnose on Peach Fruit Caused by Colletotrichum truncatum in South Carolina.

In July 2013, two diseased peach fruit (Prunus persica (L.) Stokes) of the cv. Sweet Dream were collected from a commercial orchard in Ridge Springs, South Carolina. Affected peaches were at or near maturity and symptoms resembled anthracnose disease caused by Colletotrichum spp. with circular sunken tan to brown lesions that were firm in touch, and had wrinkled concentric rings. The center of the lesion was covered with black acervuli containing setae. To isolate the causal agent, the two symptomatic fruit were surface-sterilized in 10% bleach for 2 min and rinsed with sterile distilled water. Lesions were cut in half, and necrotic tissue from the inside of the fruit was placed on acidified potato dextrose agar (APDA). Flat colonies covered with olive-gray to iron-gray acervuli developed on APDA incubated at 22°C with a 12-h cycle of fluorescent light and darkness. Morphology of acervuli, setae (avg. 90 to 160 µm), conidiophores (up to 90 um long), and conidia (avg. 22 × 3.8 µm) of single spore isolates were consistent with descriptions of Colletotrichum truncatum (Schwein.) Andrus & W.D. Moore (3), a causal agent of anthracnose disease. Genomic DNA was extracted from isolate Ct_RR13_1 using the MasterPure Yeast DNA Purification Kit (Epicentre, Madison, WI). The ribosomal ITS1-5.8S-ITS2 region and a partial sequence of the actin gene were amplified with primer pair ITS1 and ITS4 (4), and primer pair ACT-512F and ACT-783A (2), respectively. A multilocus sequence identification in Q-bank Fungi revealed a 100% similarity with C. truncatum (1). The C. truncatum sequences from the peach isolate were submitted to GenBank (accessions KF906258 and KF906259). Pathogenicity of isolate Ct_RR13_1 was confirmed by inoculating five mature but still firm peach fruits with a conidial suspension of C. truncatum. Peaches were washed with soap and water, surface-disinfected for 2 min with 10% bleach, rinsed with sterile distilled water, and air dried. Dried fruit were stabbed at three equidistant points, each about 2 cm apart, to a depth of 9.5 mm using a sterile 26G3/8 beveled needle (Becton Dickinson & Co., Rutherford, NJ). For inoculation, a 30-µl droplet of conidia suspension prepared in distilled, sterile water (1 to 2 × 104 spores/ml) was placed on each wound; control fruit received sterile water without conidia. Fruit were incubated at 22°C for 2 days at 100% humidity and another 12 days at 70% humidity. Inoculated fruit developed anthracnose symptoms with sporulating areas as described above and the fungus was re-isolated. All control fruit remained healthy. C. truncatum has a wide host range, including legumes and solanaceous plants of the tropics, and is especially common in the Fabaceae family. Its occurrence in a commercial peach orchard is worrisome because control measures may need to be developed that are different from those developed for endemic species, i.e. C. acutatum and C. gloeoporioides, due to differences in disease cycle or fungicide sensitivity. To our knowledge, this is the first report of C. truncatum causing anthracnose on a member of the genus Prunus. References: (1) P. Bonants et al. EPPO Bull. 43:211, 2013. (2) I. Carbone et al. Mycologia 91:553, 1999. (3) U. Damm et al. Fungal Divers. 39:45, 2009. (4) T. J. White et al. Pages 315-322 in: PCR Protocols: A Guide to Methods and Application. Academic Press, NY, 1993.

Reversal of morphine analgesic tolerance by ethanol in the mouse.

The chronic use of opioids in humans, accompanied by the development of tolerance, is a dangerous phenomenon in its own right. However, chronic opioid use is often made more dangerous by the coconsumption of other substances. It has been observed that the blood level of opioids in postmortem analyses of addicts, who consumed ethanol along with the opioid, was much less than that observed in individuals who died from opioids alone. This relationship between ethanol and opioids led us to investigate the hypothesis that ethanol alters tolerance to opioids. In the present study, we report that ethanol significantly and dose-dependently reduced the antinociceptive tolerance produced by morphine and the cross-tolerance between [D-Ala2,N-Me-Phe4,Gly5-ol]-enkephalin (DAMGO) and morphine in the mouse tail-flick test. The reversal of morphine tolerance was partially blocked by both the gamma receptor blocker bicuculline and by the γ-aminobutyric acid (GABA)(B) receptor blocker phaclofen and the administration of both inhibitors completely reversed the effects of ethanol on morphine tolerance. Diazepam, like ethanol, decreased morphine tolerance. However, this inhibition was reversed by the GABA(A) antagonist bicuculline but not by the GABA(B) antagonist phaclofen. These findings have important implications for individuals who abuse opioids and ethanol as well as suggest a mechanism to reduce the amount of opioid needed in chronic pain treatment.

In situ Brillouin study of sodium alumino silicate glasses under pressure.

The in situ elastic and plastic behaviors of sodium aluminosilicate glasses with different degrees of depolymerization were analyzed using Brillouin spectroscopy. The observed elastic anomaly progressively vanished with depolymerization. The densification process appears to be different from that observed in pure silica glass. In the plastic regime of densified glasses hysteresis loops were observed and related to modification of the local silicon environment facilitated by the addition of sodium.

Enhancement of µ-opioid receptor desensitization by nitric oxide in rat locus coeruleus neurons: involvement of reactive oxygen species.

It has previously been shown that nitric oxide (NO) synthase is involved in the development of opioid tolerance. The aim of the present work was to study the effect of NO on µ-opioid receptor (MOR) desensitization. Furthermore, we explored the possible role of reactive oxygen species (ROS) in this effect. Single-unit extracellular and whole-cell patch-clamp recordings were performed on locus coeruleus (LC) neurons from rat brain slices. Perfusion with high concentrations of Met(5)-enkephalin (ME) caused a concentration-related reduction of opioid effect, reflecting the induction of homologous MOR desensitization. The NO donors sodium nitroprusside and diethylamine NONOate markedly enhanced the ME-induced MOR desensitization, although the acute effect of ME on K(+) conductance was not affected by sodium nitroprusside. Continuous perfusion with the antioxidants melatonin, trolox, 21-[4-(2,6-di-1-pyrrolidinyl-4-pyrrimidinyl)-1-piperazinyl]-pregna-1,4,9(11)-triene-3,20-dione(Z)-2-butenedioate (U74389G), and diethyldithiocarbamate prevented the effect of sodium nitroprusside on MOR desensitization, but they did not themselves alter the desensitization. Like sodium nitroprusside, the ROS-generating molecule H(2)O(2) enhanced MOR desensitization induced by ME. However, α(2)-adrenoceptor desensitization induced by noradrenaline was not modified by H(2)O(2), suggesting a selective action of ROS on MOR. Our results suggest that elevated levels of NO, which may be reached in pathological processes, enhance homologous desensitization of MOR in the LC, probably through a mechanism involving ROS generation.

Anisotropic hot electron emission from fullerenes.

Photoelectron spectra for fullerenes C(60) and C(70) ionized using 800 nm laser pulses with pulse durations from 120 to 1000 fs show thermal electron kinetic energy distributions but they also exhibit angular anisotropy with respect to the laser light polarization. The effective temperature of electrons, measured along the laser polarization direction, is significantly higher than in the perpendicular direction. We explain this observation by considering that the emission of the thermal electrons is uncorrelated with the phase of the laser pulse, unlike directly ionized electrons, and, depending on the time of emission, they may experience an additional "kick" from the vector potential of the laser field when they are emitted from the molecule.

Comparative outcomes of total hip and knee arthroplasty: a prospective cohort study.

PURPOSE: The comparative outcome of primary hip and knee arthroplasty is not well understood. This study aimed to investigate the outcome and satisfaction of these procedures and determine predictive models for 1 year patient outcome with a view to informing surgical management and patient expectations. STUDY DESIGN: Prospective cohort study of all primary hip and knee arthroplasty procedures performed at the Royal Infirmary of Edinburgh between January 2006 and November 2008. General health (SF-12) and joint specific function (Oxford Score) was assessed pre-operatively and at 6 and 12 months post-operatively. Patient satisfaction was assessed at 12 months. RESULTS: 1410 total hip arthroplasty (THA) and 1244 total knee arthroplasty (TKA) procedures were assessed. Oxford Score improved by 4.9 points more in THA patients than in TKA patients. SF-12 physical scores were on average 2.7 points greater in the THA patients at one year. Satisfaction was also greater (91%) following THA compared with TKA (81%). Regression modelling was not able to predict individual patient outcome; however, mean pre-operative Oxford Scores were found to be strong predictors of mean post-operative Oxford Scores for each procedure. Age, gender and pre-operative general health scores did not influence these models. CONCLUSIONS: Both THA and TKA confer substantial improvement in patient outcome; however, greater joint specific, general health and satisfaction scores are reported following THA. This difference is physical in nature. Regression models are presented that can be applied to predict mean hip/knee arthroplasty outcome based on preoperative values.

Why the way we are living may be bad for our mental well-being, and what we might choose to do about it: responding to a 21st Century public health challenge.

With economic recession biting ever harder, rates of mental ill-health rising and levels of mental well-being falling, this article suggests that it is time to critique the progress we have made, re-evaluate what it is that makes life worth living, and consider what public health may have to offer in the 21st Century. This article focuses on three distinct areas: the public health challenge; the broader societal challenges; and suggestions for effective responses. It argues that mental well-being, both individually and collectively, is a public health resource that, until now, has been underplayed and undervalued in traditional approaches to public health. Drawing on the evidence, it promotes the need for a more integrated approach to public health for the future, pulling together action and evidence on both physical and mental health and well-being, with the ultimate aim of creating a more mentally healthy society.

Aboveground Root Collar Excavation of Peach Trees for Armillaria Root Rot Management.

Root collar excavation (RCE) has been applied to established citrus trees and grapevines for Armillaria root rot (ARR) control but, despite its demonstrated effectiveness, this cultural management system is not routinely used for ARR protection in disease-infested replant sites. One major drawback is the difficulty of excavating the belowground root collar, the potential of excavated roots to be covered again with surrounding soil, and the associated labor cost. In this study, a new cultural method was investigated that resulted in trees with aboveground excavated root collars, potentially eliminating many of the drawbacks. Experimental peach trees were planted in two commercial orchards (designated Landrum and Monetta) in South Carolina; each tree replaced one that had declined from ARR disease the year before. Trees were planted approximately 40 cm higher than normal in open-bottom Smart Pots and root collars were excavated above ground level 8 months later. Five years after planting, 30 and 70% of all control trees (planted according to grower standard) had declined from ARR disease in Landrum and Monetta, respectively, whereas only 0 and 10%, respectively, of trees in the aboveground root collar excavation (AGRCE) treatment had declined. The difference in disease pressure between the two locations could not be attributed to differences in nematode pressure. Nonexcavated trees in Smart Pots revealed significantly less tree decline (P ≤ 0.05) compared with the control but tree decline in both locations was greater compared with the AG-RCE treatment (P ≤ 0.05). Trees in the AG-RCE treatment were as vigorous as the controls but produced more root suckers. In this 'prototype' study, we demonstrate the potential of aboveground root collar excavation for ARR management. Its potential for commercial use is discussed.

Hemoglobin degradation in the human malaria pathogen Plasmodium falciparum: a catabolic pathway initiated by a specific aspartic protease.

Hemoglobin is an important nutrient source for intraerythrocytic malaria organisms. Its catabolism occurs in an acidic digestive vacuole. Our previous studies suggested that an aspartic protease plays a key role in the degradative process. We have now isolated this enzyme and defined its role in the hemoglobinolytic pathway. Laser desorption mass spectrometry was used to analyze the proteolytic action of the purified protease. The enzyme has a remarkably stringent specificity towards native hemoglobin, making a single cleavage between alpha 33Phe and 34Leu. This scission is in the hemoglobin hinge region, unraveling the molecule and exposing other sites for proteolysis. The protease is inhibited by pepstatin and has NH2-terminal homology to mammalian aspartic proteases. Isolated digestive vacuoles make a pepstatin-inhibitable cleavage identical to that of the purified enzyme. The pivotal role of this aspartic hemoglobinase in initiating hemoglobin degradation in the malaria parasite digestive vacuoles is demonstrated.

The effect of protein kinase C and G protein-coupled receptor kinase inhibition on tolerance induced by mu-opioid agonists of different efficacy.

Differences in the mechanisms underlying tolerance and mu-opioid receptor desensitization resulting from exposure to opioid agonists of different efficacy have been suggested previously. The objective of this study was to determine the effects of protein kinase C (PKC) and G protein-coupled receptor kinase (GRK) inhibition on antinociceptive tolerance in vivo to opioid agonists of different efficacy. A rapid (8-h) tolerance-induction model was used where each opioid was repeatedly administered to naive mice. Animals were then challenged with the opioid after injection of a kinase inhibitor to determine its effects on the level of tolerance. Tolerance to meperidine, morphine, or fentanyl was fully reversed by the PKC inhibitor 12-(2-cyanoethyl)-6,7,12,13-tetrahydro-13-methyl-5-oxo-5H-indolo(2,3-a)pyrrolo(3,4-c)carbazole (Gö6976). However, in vivo tolerance to [d-Ala(2),N-Me-Phe(4),Gly(5)-ol]-enkephalin (DAMGO) was not reversed by PKC inhibition. The novel small-molecule GRK inhibitors beta-adrenergic receptor kinase 1 inhibitor and 2-(8-[(dimethylamino) methyl]-6,7,8,9-tetrahydropyridol[1,2-a]indol-3-yl)-3-(1-methylindol-3-yl)maleimide (Ro 32-0432) did not reverse the tolerance to meperidine, fentanyl, or morphine but did reverse the tolerance to DAMGO. To correlate GRK-dependent DAMGO-induced tolerance with mu-opioid receptor desensitization, we used in vitro whole-cell patch-clamp recording from mouse locus coeruleus neurons and observed that the GRK inhibitors reduced DAMGO-induced desensitization of mu-opioid receptors, whereas the PKC inhibitor had no effect. These results suggest that tolerance induced by low- and moderate-efficacy mu-opioid receptor agonists is dependent on PKC, whereas tolerance induced by the high-efficacy agonist DAMGO is dependent on GRK.

Patient perspectives of Condition Management Programmes as a route to better health, well-being and employability.

BACKGROUND: Condition Management Programmes (CMPs), delivered through primary care settings, have been identified as possible vehicles to facilitate return to work for individuals with chronic health problems. There is little research, however, which examines how such programmes are received by patients. OBJECTIVE: To explore patients' experiences of CMPs in terms of health, well-being and employability. METHODS: Four focus groups and nine semi-structured interviews were conducted in order to capture patients' (n = 25) perceptions and experiences regarding participation in one of five different CMPs: Cardiac Rehabilitation, Counselling, Lower Back Pain Services, Smoking Cessation and a GP Exercise Referral Programme. RESULTS: Experiences of the CMPs were generally positive. Respondents reported improved health behaviours (specifically better diets and increased exercise), positive psychosocial outcomes (including increased self-esteem, confidence and social support) and in some cases, return to work. However, concerns were expressed about the shortness of interventions and their accessibility. CONCLUSIONS: Although condition management appears to have been well received by participants, the findings also illustrate that there is no 'one size fits all' template for CMPs. Rather, interventions should be adapted to take account of the dynamics of specific conditions, the context in which the intervention is based and the characteristics of the individuals involved.

Role of protein kinase C and mu-opioid receptor (MOPr) desensitization in tolerance to morphine in rat locus coeruleus neurons.

In morphine tolerance a key question that remains to be answered is whether mu-opioid receptor (MOPr) desensitization contributes to morphine tolerance, and if so by what cellular mechanisms. Here we demonstrate that MOPr desensitization can be observed in single rat brainstem locus coeruleus (LC) neurons following either prolonged (> 4 h) exposure to morphine in vitro or following treatment of animals with morphine in vivo for 3 days. Analysis of receptor function by an operational model indicated that with either treatment morphine could induce a profound degree (70-80%) of loss of receptor function. Ongoing PKC activity in the MOPr-expressing neurons themselves, primarily by PKCalpha, was required to maintain morphine-induced MOPr desensitization, because exposure to PKC inhibitors for only the last 30-50 min of exposure to morphine reduced the MOPr desensitization that was induced both in vitro and in vivo. The presence of morphine was also required for maintenance of desensitization, as washout of morphine for > 2 h reversed MOPr desensitization. MOPr desensitization was homologous, as there was no change in alpha(2)-adrenoceptor or ORL1 receptor function. These results demonstrate that prolonged morphine treatment induces extensive homologous desensitization of MOPrs in mature neurons, that this desensitization has a significant PKC-dependent component and that this desensitization underlies the maintenance of morphine tolerance.

Opiates and opioid peptides hyperpolarize locus coeruleus neurons in vitro.

Intracellular recordings were made from locus coeruleus neurons in a brain slice preparation. Opiates and opioid peptides produced a dose-dependent, stereospecific, naloxone-reversible hyperpolarization of the neuronal membrane. This was associated with an increase in membrane conductance.

Virus-induced neuronal apoptosis blocked by the herpes simplex virus latency-associated transcript.

Latent infections with periodic reactivation are a common outcome after acute infection with many viruses. The latency-associated transcript (LAT) gene is required for wild-type reactivation of herpes simplex virus (HSV). However, the underlying mechanisms remain unclear. In rabbit trigeminal ganglia, extensive apoptosis occurred with LAT(-) virus but not with LAT(+) viruses. In addition, a plasmid expressing LAT blocked apoptosis in cultured cells. Thus, LAT promotes neuronal survival after HSV-1 infection by reducing apoptosis.