bluuebunny/crossref_metadata_2025 huggingface dataset:
Overview of the lipid formulations of amphotericin B
Authors: Dupont Bertrand
Published: January 2012

Invasive fungal infections have been increasingly recognized as a major cause of morbidity and mortality in the immunocompromised host. Amphotericin B has a broad spectrum and has remained the drug of choice for life-threatening invasive fungal infections. However, adverse events, particularly renal insufficiency, are limiting factors in achieving an effective dose: the prescription of amphotericin B is a compromise between toxicity and efficacy. Lipid formulations offer a better therapeutic index by circumscribing amphotericin B toxicity. Three lipid formulations are available in most countries: AmBisome, the only true liposome; Abelcet, with a ribbon-like structure; and Amphocil/Amphotec, composed of disc-like structures. All these formulations contain amphotericin B, but they differ in shape, size, reticuloendothelial clearance, Cmax, AUC and visceral diffusion. The impact of these differences in pharmacokinetics and pharmacodynamics on clinical efficacy is still unclear. Efficacy has been shown in neutropenic patients with fever of unknown origin, systemic candidosis, invasive aspergillosis, cryptococcal meningitis and a variety of other difficult-to-treat mycoses, such as Fusarium or Zygomycetes infections. The effective dose may vary from one formulation to the other and is c. 3–5 mg/kg/day. All formulations are less nephrotoxic than amphotericin B. In one randomized double-blind study, AmBisome 3 or 5 mg/kg/day was less nephrotoxic and gave fewer infusion-related events than Abelcet 5 mg/kg/day. Abelcet induces fewer infusion-related side effects than Amphocil. All formulations seem at least as effective as amphotericin B. In some patients with life-threatening mycosis who failed treatment with, or were intolerant to, amphotericin B, the lipid formulations were effective. Further studies with comparable selected high-risk patients are warranted to clarify the usefulness and the indications of each of the formulations. Cost is a factor limiting prescription in many institutions, where use is often restricted to patients intolerant of, or refractory to, amphotericin B.
Amphotericin B nephrotoxicity
Authors: Deray Gilbert
Published: January 2012

The use of amphotericin B limited by dose-dependent nephrotoxicity. Elevated creatinine associated with amphotericin B is not only a marker for renal dysfunction, but is also linked to an increase in hospital costs and a substantial risk for the use of haemodialysis and a higher mortality rate. Therefore, amphotericin B nephrotoxicity is not a benign complication and its prevention is essential. Several manipulations have been proposed to minimize amphotericin B-induced nephrotoxicity. Mannitol and frusemide administration are reported to be protective based on anecdotal observational reports. Small prospective and randomized trials do not suggest a protective effect. Three new formulations have been developed in attempts to improve both efficacy and tolerability: amphotericin B in a lipid complex (ABLC; Abelcet); amphotericin B colloidal dispersion; and liposomal amphotericin B (AmBisome). Three prospective randomized studies have clearly shown that AmBisome is less nephrotoxic than amphotericin B. In a double-blind randomized trial significantly fewer patients receiving AmBisome had nephrotoxic effects. This significant reduction in azotaemia was also observed among subgroups of patients receiving concomitant therapy with nephrotoxic agents. Moreover, there were fewer patients with hypokalaemia in the group receiving AmBisome. A recent multicentre double-blind study has shown that AmBisome (3 or 5 mg/kg/day) has a better safety profile than Abelcet (5 mg/kg). Patients in both AmBisome treatment groups experienced less chills/rigors, less nephrotoxicity based on a doubling of serum creatinine, and fewer toxic reactions resulting in discontinuation of therapy. In conclusion, amphotericin B nephrotoxicity is observed frequently. It clearly increases patient mortality. Nephrotoxicity must be recognized early, based on tubular abnormalities and a mild increase in serum creatinine. Its prevention relies on the detection and suppression of risk factors and the use of AmBisome.
AmBisome in the treatment of fungal infections: the UK experience
Authors: Chopra Rajesh
Published: January 2012

Despite a number of recent advances in diagnosis and treatment strategies, fungal infections remain an important cause of morbidity and mortality in neutropenic and immunosuppressed patients. The main fungal infections are candidosis and aspergillosis, although an increased incidence of rarer fungal infections including Fusarium spp., Aurebasidium pullulans and Mucor spp. has been noted. Mortality may be decreased with earlier diagnosis and aggressive treatment with lipid-associated amphotericin B. Invasive pulmonary aspergillosis (IPA) in the neutropenic host presents particular challenges in terms of diagnosis and therapy. We undertook a prospective study over a 36 month period to link the status of early diagnosis and early aggressive therapy with lipid-associated amphotericin B. Early investigation comprised the use of bronchoscopy and bronchoalveolar lavage together with real-time PCR to detect Aspergillus spp. This combined approach revealed the incidence of proven or probable IPA to be 19%. Early therapy resulted in no mortality from IPA. In treating the rarer fungal species, AmBisome was found to be the most effective agent, and could be used at doses of up to 12 mg/kg with few side effects.
Liposomal amphotericin B (AmBisome): efficacy and safety of low-dose therapy in pulmonary fungal infections
Authors: Lequaglie Cosimo
Published: January 2012

A prospective study of the treatment of fungal infections with low-dose AmBisome enrolled 36 of 52 patients with thoracic malignancies who developed pulmonary fungal infections in the National Cancer Centre, Milan, over a 3.5 year period. Thirty-three high-risk patients had received standard prophylaxis with iv fluconazole. In these patients, symptoms indicating deep mycosis were detected after 7–9 days of primary prophylactic therapy. Another three patients, not treated with fluconazole, showed similar symptoms. Bronchoalveolar lavage, blood culture and/or CT scan of chest diagnosed invasive aspergillosis in 29 patients and deep invasive Candida infection in seven. AmBisome was given at 1–2.2 mg/kg/day iv for 10 days to avoid or decrease toxicity normally induced by amphotericin B. The fungal infection was eradicated in all 36 patients. Negative cultures were obtained after 5 or 6 days of antifungal treatment. No adverse reactions attributed to AmBisome were detected. After a follow up of 5–48 months, 30 patients were still alive. Six patients had died, two due to adult respiratory distress syndrome and four due to progression of cancer. No mycotic relapses or reinfections were detected during follow up. In a subset of critically ill patients with thoracic malignancies, the administration of low-dose liposomal amphotericin B (AmBisome) resulted in complete eradication of pulmonary Aspergillus and Candida infections, and was remarkably well tolerated.
Ten years' experience with liposomal amphotericin B in transplant recipients at Huddinge University Hospital
Authors: Ringdén Olle
Published: January 2012

Our substantial experience in several trials with AmBisome in adult and paediatric patients undergoing transplantation has shown this formulation of amphotericin B to be safe and effective in therapeutic and prophylactic use. AmBisome has shown a significant reduction in fungal colonization and invasive Candida infections compared with placebo in a prospec-tive, double-blind study in bone marrow transplantation, and eradication of invasive fungal infections in 86% of 14 children undergoing bone marrow transplantation. The main side effects of AmBisome use are elevations in serum potassium and creatinine, but these lead to very few withdrawals from treatment. Compared with conventional amphotericin B, AmBisome is very expensive, but its much improved safety profile and proven efficacy make it an excellent agent for management of invasive fungal disease in transplant recipients.
Cryptococcosis in Australasia and the treatment of cryptococcal and other fungal infections with liposomal amphotericin B
Authors:   the Australasian Society for Infectious Diseases (ASID) Mycoses Interest Group, Chen Sharon C. A.
Published: January 2012

Cryptococcus neoformans is an important fungal pathogen in both immunocompromised and immunocompetent hosts. The mean annual incidence during 1994–1997 was 6.6 cases per million people per year in Australia, and 2.2 cases per million people per year in New Zealand. C. neoformans var. neoformans caused 85% of 312 episodes (98% of episodes in immunocompromised hosts) and C. neoformans var. gattii caused 15% (44% in immunocompetent hosts). The AIDS-specific incidence declined significantly over the 3 years. Mortality from cryptococcosis remains substantial. In trials involving small numbers of AIDS patients, liposomal amphotericin B (AmBisome) was found to be active against C. neoformans, with mycological response rates of 67–85%; however, maintenance therapy with an oral antifungal agent is required indefinitely. In a randomized study of patients with cryptococcal meningitis, AmBisome (4 mg/kg/day) produced mycological eradication in 73% of patients compared with 38% with conventional amphotericin. AmBisome resulted in significantly earlier sterilization of cerebrospinal fluid than conventional amphotericin (7–14 days versus 21 days) and was less nephrotoxic. The benefit of this reduced toxicity is denied to many patients because of an enormous cost barrier. In a survey of the practices of clinical mycologists in Australia, 11 experts responded to a questionnaire survey regarding the use of available lipid preparations. Their indications for use as initial therapy were mucormycosis (7/10), renal failure (7/10), Fusarium infection (2/10) and aspergillosis (2/10). Cryptococcosis, candidosis and febrile neutropenia were rarely regarded as an indication; failed therapy with conventional amphotericin was an indication to use AmBisome for 8/11 respondents. The majority believed that AmBisome was equivalent to conventional amphotericin, with amphotericin B lipid complex and AmBisome equivalent to each other in terms of efficacy. The main barrier to replacement of conventional amphotericin with lipid preparations was seen as an issue of cost.
Suspected infection in children with cancer
Authors: Shaw Peter J.
Published: January 2012

A common complication of the intensive therapy that children with cancer receive is infection. The Oncology Unit of The Children's Hospital at Westmead maintains a comprehensive database of all admissions for suspected sepsis. From July 1994 to June 1999 broad-spectrum antibiotics were commenced in 2331 episodes. With early and aggressive use of empirical amphotericin B, 545 courses were given. Bacteraemia was documented in 701 episodes and invasive fungal disease in 73. Trends seen during the study included: (i) the proportion of febrile neutropenic patients receiving granulocyte colony stimulating factor increased from 40% to 60%; (ii) the mean neutrophil count at cessation of antibiotics fell from 0.97 to 0.63 × 109 cells/L for patients not receiving growth factors; (iii) the proportion of non-albicans Candida species infections increased. In addition, an outbreak of infection caused by Scedosporium sp. was documented; (iv) first-line empirical antibiotic combinations containing vancomycin fell from 20% to 7%; and (v) the ability to maintain or escalate anti-fungal therapy with reduced nephrotoxicity through use of lipid formulations of amphotericin was increasingly apparent in high-risk patients. During the study, infection was the primary cause of death in 11 non-bone marrow transplant (BMT) patients (five fungal, four viral, one bacterial infection and one sepsis syndrome) and five BMT patients (two bacterial and three viral). A prospective randomized study of toxicity due to amphotericin B given in either lipid emulsion or dextrose showed no significant difference, but both groups showed a lower incidence of amphotericin B intolerance in comparison with the adult series. The inability to reduce toxicity of amphotericin B by simple mixing with lipid emulsion has led to increasing use of commercially available lipid formulations of amphotericin B.
The price of your soul: neural evidence for the non-utilitarian representation of sacred values
Authors: Berns Gregory S. , Bell Emily , Capra C. Monica , Prietula Michael J. , Moore Sara , Anderson Brittany , Ginges Jeremy , Atran Scott
Published: January 2012

Sacred values, such as those associated with religious or ethnic identity, underlie many important individual and group decisions in life, and individuals typically resist attempts to trade off their sacred values in exchange for material benefits. Deontological theory suggests that sacred values are processed based on rights and wrongs irrespective of outcomes, while utilitarian theory suggests that they are processed based on costs and benefits of potential outcomes, but which mode of processing an individual naturally uses is unknown. The study of decisions over sacred values is difficult because outcomes cannot typically be realized in a laboratory, and hence little is known about the neural representation and processing of sacred values. We used an experimental paradigm that used integrity as a proxy for sacredness and which paid real money to induce individuals to sell their personal values. Using functional magnetic resonance imaging (fMRI), we found that values that people refused to sell (sacred values) were associated with increased activity in the left temporoparietal junction and ventrolateral prefrontal cortex, regions previously associated with semantic rule retrieval. This suggests that sacred values affect behaviour through the retrieval and processing of deontic rules and not through a utilitarian evaluation of costs and benefits.
Implicit signals in small group settings and their impact on the expression of cognitive capacity and associated brain responses
Authors: Kishida Kenneth T. , Yang Dongni , Quartz Karen Hunter , Quartz Steven R. , Montague P. Read
Published: January 2012

Measures of intelligence, when broadcast, serve as salient signals of social status, which may be used to unjustly reinforce low-status stereotypes about out-groups' cultural norms. Herein, we investigate neurobehavioural signals manifest in small (
n
= 5) groups using functional magnetic resonance imaging and a ‘ranked group IQ task’ where implicit signals of social status are broadcast and differentiate individuals based on their expression of cognitive capacity. We report an initial overall decrease in the expression of cognitive capacity in the small group setting. However, the environment of the ‘ranked group IQ task’ eventually stratifies the population into two groups (‘high performers’, HP and ‘low performers’, LP) identifiable based on changes in estimated intelligence quotient and brain responses in the amygdala and dorsolateral prefrontal cortex. In addition, we demonstrate signals in the nucleus accumbens consistent with prediction errors in expected changes in status regardless of group membership. Our results suggest that individuals express diminished cognitive capacity in small groups, an effect that is exacerbated by perceived lower status within the group and correlated with specific neurobehavioural responses. The impact these reactions have on intergroup divisions and conflict resolution requires further investigation, but suggests that low-status groups may develop diminished capacity to mitigate conflict using non-violent means.
The neural basis of cultural differences in delay discounting
Authors: Kim Bokyung , Sung Young Shin , McClure Samuel M.
Published: January 2012

People generally prefer to receive rewarding outcomes sooner rather than later. Such preferences result from delay discounting, or the process by which outcomes are devalued for the expected delay until their receipt. We investigated cultural differences in delay discounting by contrasting behaviour and brain activity in separate cohorts of Western (American) and Eastern (Korean) subjects. Consistent with previous reports, we find a dramatic difference in discounting behaviour, with Americans displaying much greater present bias and elevated discount rates. Recent neuroimaging findings suggest that differences in discounting may arise from differential involvement of either brain reward areas or regions in the prefrontal and parietal cortices associated with cognitive control. We find that the ventral striatum is more greatly recruited in Americans relative to Koreans when discounting future rewards, but there is no difference in prefrontal or parietal activity. This suggests that a cultural difference in emotional responsivity underlies the observed behavioural effect. We discuss the implications of this research for strategic interrelations between Easterners and Westerners.
Social cognition in members of conflict groups: behavioural and neural responses in Arabs, Israelis and South Americans to each other's misfortunes
Authors: Bruneau Emile G. , Dufour Nicholas , Saxe Rebecca
Published: January 2012

In contexts of cultural conflict, people delegitimize the other group's perspective and lose compassion for the other group's suffering. These psychological biases have been empirically characterized in intergroup settings, but rarely in groups involved in active conflict. Similarly, the basic brain networks involved in recognizing others' narratives and misfortunes have been identified, but how these brain networks are modulated by intergroup conflict is largely untested. In the present study, we examined behavioural and neural responses in Arab, Israeli and South American participants while they considered the pain and suffering of individuals from each group. Arabs and Israelis reported feeling significantly less compassion for each other's pain and suffering (the ‘conflict outgroup’), but did not show an ingroup bias relative to South Americans (the ‘distant outgroup’). In contrast, the brain regions that respond to others' tragedies showed an ingroup bias relative to the distant outgroup but
not
the conflict outgroup, particularly for descriptions of emotional suffering. Over all, neural responses to conflict group members were qualitatively different from neural responses to distant group members. This is the first neuroimaging study to examine brain responses to others' suffering across both distant and conflict groups, and provides a first step towards building a foundation for the biological basis of conflict.
Ascribing beliefs to ingroup and outgroup political candidates: neural correlates of perspective-taking, issue importance and days until the election
Authors: Falk Emily B. , Spunt Robert P. , Lieberman Matthew D.
Published: January 2012

We used the five weeks leading up to the 2008 presidential election as a backdrop to examine the ways that the brain processes attitudes and beliefs under different circumstances. We examined individual differences in personal issue importance and trait perspective-taking, as well as the temporal context in which attitude representation took place (i.e. number of days until the election). Finally, we examined the extent to which similar or dissimilar processes were recruited when considering the attitudes of political ingroup and outgroup candidates. Brain regions involved in social cognition and theory of mind, and to a lesser extent the limbic system, were modulated by these factors. Higher issue importance led to greater recruitment of neural regions involved in social cognition, across target perspectives. Higher trait perspective-taking was also associated with greater recruitment of several regions involved in social cognition, but differed depending on target perspective; greater activity was observed in prefrontal regions associated with social cognition when considering the perspective of one's own candidate compared with the opponent, and this effect was amplified closer to the election. Taken together, these results highlight ways in which ability and motivational relevance modulate socio-affective processing of the attitudes of others.
The cultural contagion of conflict
Authors: Gelfand Michele , Shteynberg Garriy , Lee Tiane , Lun Janetta , Lyons Sarah , Bell Chris , Chiao Joan Y. , Bruss C. Bayan , Al Dabbagh May , Aycan Zeynep , Abdel-Latif Abdel-Hamid , Dagher Munqith , Khashan Hilal , Soomro Nazar
Published: January 2012

Anecdotal evidence abounds that conflicts between two individuals can spread across networks to involve a multitude of others. We advance a cultural transmission model of intergroup conflict where conflict contagion is seen as a consequence of universal human traits (ingroup preference, outgroup hostility; i.e. parochial altruism) which give their strongest expression in particular cultural contexts. Qualitative interviews conducted in the Middle East, USA and Canada suggest that parochial altruism processes vary across cultural groups and are most likely to occur in collectivistic cultural contexts that have high ingroup loyalty. Implications for future neuroscience and computational research needed to understand the emergence of intergroup conflict are discussed.
The biology of cultural conflict
Authors: Berns Gregory S. , Atran Scott
Published: January 2012

Although culture is usually thought of as the collection of knowledge and traditions that are transmitted outside of biology, evidence continues to accumulate showing how biology and culture are inseparably intertwined. Cultural conflict will occur only when the beliefs and traditions of one cultural group represent a challenge to individuals of another. Such a challenge will elicit brain processes involved in cognitive decision-making, emotional activation and physiological arousal associated with the outbreak, conduct and resolution of conflict. Key targets to understand bio-cultural differences include primitive drives—how the brain responds to likes and dislikes, how it discounts the future, and how this relates to reproductive behaviour—but also higher level functions, such as how the mind represents and values the surrounding physical and social environment. Future cultural wars, while they may bear familiar labels of religion and politics, will ultimately be fought over control of our biology and our environment.
The unfolded protein response at the crossroads of cellular life and death during endoplasmic reticulum stress
Authors: Jäger Richard , Bertrand Mathieu J.M. , Gorman Adrienne M. , Vandenabeele Peter , Samali Afshin
Published: January 2012

One of the early cellular responses to endoplasmic reticulum (ER) stress is the activation of the unfolded protein response (UPR). ER stress and the UPR are both implicated in numerous human diseases and pathologies. In spite of this, our knowledge of the molecular mechanisms that regulate cell fate following ER stress is limited. The UPR is initiated by three ER transmembrane receptors: PKR‐like ER kinase (PERK), activating transcription factor (ATF) 6 and inositol‐requiring enzyme 1 (IRE1). These proteins sense the accumulation of unfolded proteins and their activation triggers specific adaptive responses to resolve the stress. Intriguingly, the very same receptors can initiate signalling pathways that lead to apoptosis when the attempts to resolve the ER stress fail. In this review, we describe the known pro‐apoptotic signalling pathways emanating from activated PERK, ATF6 and IRE1 and discuss how their signalling switches from an adaptive to a pro‐apoptotic response.
Development and characterization of novel cell lines from Etroplus suratensis and their applications in virology, toxicology and gene expression
Authors: Sarath Babu V. , Chandra V. , Nambi K. S. N. , Majeed S. A. , Taju G. , Patole M. S. , Hameed A. S. S.
Published: January 2012

Four novel cell lines from tissues of eye, gill, kidney and brain of Etroplus suratensis were developed and characterized. The cell lines of eye, gill, kidney and brain were sub‐cultured for 245, 185, 170 and 90 passages, respectively, since 2008. These cell lines showed predominantly epithelial‐like cells. Effects of temperature and foetal bovine serum concentration on the growth of these cell lines were examined and optimum growth was found at the temperature of 28° C with 20% foetal bovine serum. All the four cell lines were successfully cryopreserved and revived at different passage levels. Cell‐cycle analysis of these cell lines was carried out by fluorescence‐activated cell sorting. Polymerase chain reaction (PCR) products obtained from the cells and tissues of E. suratensis with primers specific to the conserved region of 16S ribosomal RNA and cytochrome oxidase I genes of E. suratensis revealed the origin of cell lines from E. suratensis. Antibodies raised against the tissues and cells of eye, kidney and gill were highly cross reacted to their specific tissue and cells of E. suratensis. Chromosomal analysis revealed that E. suratensis cells have a normal diploid karyotype with 2n = 48. The cells of these cell lines were successfully transfected with pEGFP vector DNA. The eye (IEE), gill (IEG) and kidney (IEK) cell lines were found to be susceptible to nodavirus but resistant to infectious pancreatic necrosis virus (IPNV). The cells of gill, kidney and eye were applied to test the cytotoxicity of tannery effluents.
Addiction research centres and the nurturing of creativity. The Korean Institute on Alcohol Problems (KIAP)
Authors: Chun Sungsoo , Reid Easton A. , Sohn Aeree , Welch Michael E. , Yun‐Welch Sunmee , Yun Mieun
Published: January 2012

The aim of this paper is to provide an account of the history, current status and vision of the Korean Institute on Alcohol Problems (KIAP). In the context of increasing alcohol consumption, rising second‐hand effects and industry‐friendly government policy, the Korean College Alcohol Study (KCAS) was established in the Republic of Korea in 1999, and changed its name to the Korean Institute on Alcohol Problems (KIAP) in 2005. KIAP's mission is to decrease alcohol consumption and its related harms by promoting research, advocating policy, developing intervention programmes and preparing media communications. Since 1999, KIAP has published scientific papers and books in alcohol research and used the internet and other media for dissemination of specialized information to the general population. In the last decade, KIAP has trained front‐line alcohol researchers, and advanced domestic and international networks to promote evidence‐based alcohol control policy in Korea. The light of hope shines brightly as KIAP grows and establishes critical linkages to move forward in its mission.
Respiratory arrest in an obstetric patient using remifentanil patient‐controlled analgesia*
Authors: Bonner J. C. , McClymont W.
Published: January 2012

Remifentanil patient‐controlled analgesia is well established in many centres and provides satisfactory pain relief for many women in labour. We describe a patient using remifentanil patient‐controlled analgesia who suffered a respiratory arrest requiring a brief period of ventilation. In our institution, remifentanil patient‐controlled analgesia has been offered to women in labour since 2009. Up to this point, we had not observed any critical incidents in over 130 patients using this mode of analgesia in our labour suite.
A tale of two intrusions—where familiar rock names no longer suffice
Authors: Brooks Kent
Published: January 2012

Two contrasting intrusions in Greenland are described which both have extreme compositions and mineralogy. Ilímaussaq is part of the Mezoproterozoic Gardar Province of southern West Greenland. It developed by extreme fractionation in the crust of non‐remarkable weakly alkaline basic magmas leading to extraordinarily high levels of many rare elements. Indeed, in this intrusion the zirconium mineral, eudialyte, attains rock‐forming status. Gardiner in the East Greenland sector of the Palaeogene North Atlantic Igneous Province, was formed from nephelinitic magmas formed at great depth in the mantle by very low degrees of partial melting. Here, the magmas were so silica‐poor that there are large amounts of rocks composed of the melilite group of minerals, generally with perovskite (CaTiO4) as a major phase. Thus, extreme compositions at Ilímaussaq were caused by fractionation to very small amounts of melt while at Gardiner it was caused by very small degrees of mantle melting. Both intrusions are known for fine specimens of rare minerals; in the case of Ilímaussaq over 200 have been described. Rocks such as those found here require their own names as they cannot be accommodated in the usual petrological nomenclature.
Natural aggregates in the performance and durability of concrete: chemical characteristics
Authors: Fookes Peter G. , Walker Mike J.
Published: January 2012

This article continues from the earlier feature in Geology Today (2011, v.27, n.4) and looks at the influence of chemical reactivity within concrete due to the presence of unsound aggregates or deleterious material incorporated in the aggregate used in the concrete mix. Some of the more disruptive problems from chemical unsoundness come from the presence of chlorides, which cause rusting in reinforced concrete or, sulphate attack from ground waters. Both of these reactions are relatively common in Britain. Alkali–silica reactions with aggregates and cement is not too prevalent in Britain but can be very prevalent and disruptive elsewhere in the world.
Fossil ‘treasure trove’ found in British Geological Survey vaults
Authors: Falcon‐Lang Howard
Published: January 2012

The British Geological Survey is home to more than three million fossils collected over two centuries and catalogued with enormous precision. However, as generations of curators have come and gone, a few collections have lain forgotten and their significance has gradually passed out of memory. Six months ago, I pulled opened some drawers marked ‘unregistered fossil plants’ in one of the Survey's windowless vaults in Keyworth, in central England. What I found inside made my jaw drop. Contained within were hundreds of beautiful thin sections of fossil wood dating from the early nineteenth century. The collection was assembled by botanist Joseph Hooker (Darwin's best friend) while he was briefly employed by the Survey in 1846. The material includes some of the first thin sections ever made by William Nicol, the pioneer of petrography, in the late 1820s, as well as specimens picked up by Darwin and Hooker on their round‐the‐world voyages in the 1830s and 1840s. The collection is particularly interesting in the way it sheds light on the vibrant and sometimes murky world of early nineteenth century science. This is the story of these fascinating fossils.
Yosemite—the Incomparable Valley
Authors: Waltham Tony
Published: January 2012

Cut deep into the heart of California's Sierra Nevada, the Yosemite Valley has been dubbed the Incomparable Valley, because it is so seriously spectacular. And it is. It has also been called the finest example of a deep glaciated trough. But it's not. Yosemite is more than that, and the glaciation is only part of its splendid geological story.
Does anthropogenic nitrogen deposition induce phosphorus limitation in herbivorous insects?
Authors: Tao Leiling , Hunter Mark D.
Published: January 2012

Anthropogenic nitrogen deposition has shifted many ecosystems from nitrogen (N) limitation to phosphorus (P) limitation. Although well documented in plants, no study to date has explored whether N deposition exacerbates P limitation at higher trophic levels, or focused on the effects of induced plant P limitation on trophic interactions. Insect herbivores exhibit strict N : P homeostasis, and should therefore be very sensitive to variations in plant N : P stoichiometry and prone to experiencing deposition‐induced P limitation. In the current study, we investigated the effects of N deposition and P availability on a plant‐herbivorous insect system. Using common milkweed (Asclepias syriaca) and two of its specialist herbivores, the monarch caterpillar (Danaus plexippus) and milkweed aphid (Aphis asclepiadis) as our study system, we found that experimental N deposition caused P limitation in milkweed plants, but not in either insect species. However, the mechanisms for the lack of P limitation were different for each insect species. The body tissues of A. asclepiadis always exhibited higher N : P ratios than that of the host plant, suggesting that the N demand of this species exceeds P demand, even under high N deposition levels. For D. plexippus, P addition increased the production of latex, which is an important defense negatively affecting D. plexippus growth rate. As a result, we illustrate that P limitation of herbivores is not an inevitable consequence of anthropogenic N deposition in terrestrial systems. Rather, species‐specific demands for nutrients and the defensive responses of plants combine to determine the responses of herbivores to P availability under N deposition.
Land‐atmosphere exchange of methane from soil thawing to soil freezing in a high‐Arctic wet tundra ecosystem
Authors: Tagesson Torbern , Mölder Meelis , Mastepanov Mikhail , Sigsgaard Charlotte , Tamstorf Mikkel P. , Lund Magnus , Falk Julie M. , Lindroth Anders , Christensen Torben R. , Ström Lena
Published: January 2012

The land‐atmosphere exchange of methane (CH4) and carbon dioxide (CO2) in a high‐Arctic wet tundra ecosystem (Rylekærene) in Zackenberg, north‐eastern Greenland, was studied over the full growing season and until early winter in 2008 and from before snow melt until early winter in 2009. The eddy covariance technique was used to estimate CO2 fluxes and a combination of the gradient and eddy covariance methods was used to estimate CH4 fluxes. Small CH4 bursts were observed during spring thawing 2009, but these existed during short periods and would not have any significant effect on the annual budget. Growing season CH4 fluxes were well correlated with soil temperature, gross primary production, and active layer thickness. The CH4 fluxes remained low during the entire autumn, and until early winter. No increase in CH4 fluxes were seen as the soil started to freeze. However, in autumn 2008 there were two CH4 burst events that were highly correlated with atmospheric turbulence. They were likely associated with the release of stored CH4 from soil and vegetation cavities. Over the measurement period, 7.6 and 6.5 g C m−2 was emitted as CH4 in 2008 and in 2009, respectively. Rylekærene acted as a C source during the warmer and wetter measurement period 2008, whereas it was a C sink for the colder and drier period of 2009. Wet tundra ecosystems, such as Rylekærene may thus play a more significant role for the climate in the future, as temperature and precipitation are predicted to increase in the high‐Arctic.
Modeling biophysical controls on canopy foliage water 18O enrichment in wheat and corn
Authors: Xiao Wei , Lee Xuhui , Wen Xuefa , Sun Xiaomin , Zhang Shichun
Published: January 2012

Leaf water 18O enrichment is an important factor controlling the H218O, C18OO, and O18O exchanges between the biosphere and the atmosphere. At present, there is limited capacity to explain the enrichment mechanisms in field conditions. In this study, three models of varying complexity were used to simulate the leaf water 18O enrichment at the canopy scale. Comparisons were made among the models and with high‐frequency isotopic measurements of ecosystem water pools in wheat and corn. The results show that the steady state assumption was a better approximation for ecosystems with lower canopy resistance, that it is important to consider the effect of leaf water turnover in modeling the enrichment and not necessary to deal with time changes in leaf water content, and that the leaf‐scale Péclet effect was incompatible with the big‐leaf modeling framework for canopy‐air interactions. After turbulent diffusion has been accounted for in an apparent kinetic factor parameterization, the mean 18O composition of the canopy foliage water was a well‐behaved property predictable according to the principles established by leaf‐scale studies, despite substantial variations in the leaf water enrichment with leaf and canopy positions. In the online supplement we provided a discussion on the observed variability of leaf water 18O composition with leaf and canopy positions and on the procedure for correcting isotopic measurements for organic contamination.
Natural killer T cells suppress zymosan A‐mediated granuloma formation in the liver by modulating interferon‐γ and interleukin‐10
Authors: Kobayashi Takahiro , Kawamura Hiroki , Kanda Yasuhiro , Matsumoto Hiroaki , Saito Suguru , Takeda Kazuyoshi , Kawamura Toshihiko , Abo Toru
Published: January 2012

Wild‐type (WT) and CD1d−/− [without natural killer (NK) T cells] mice were treated with zymosan A to induce granuloma formation in the liver. Increased granuloma formation was seen in NKT‐less mice on days 7 and 14 after administration. WT mice showed limited granuloma formation, and zymosan A eventually induced NKT cell accumulation as identified by their surface marker (e.g. CD1d‐tetramer). Zymosan A augmented the expression of Toll‐like receptor 2 on the cell surface of both macrophages and NKT cells. One possible reason for accelerated granuloma formation in NKT‐less mice was increased production of interferon‐ γ (IFN‐γ); a theory that was confirmed using IFN‐γ−/− mice. Also, zymosan A increased interleukin‐10 production in WT mice, which suppresses IFN‐γ production. Taken together, these results suggest that NKT cells in the liver have the potential to suppress zymosan A‐mediated granuloma formation.
Lower numbers of natural killer T cells in HIV‐1 and Mycobacterium leprae co‐infected patients
Authors: Carvalho Karina I. , Bruno Fernanda R. , Snyder‐Cappione Jennifer E. , Maeda Solange M. , Tomimori Jane , Xavier Marilia B. , Haslett Patrick A. , Nixon Douglas F. , Kallas Esper G.
Published: January 2012

Natural killer T (NKT) cells are a heterogeneous population of lymphocytes that recognize antigens presented by CD1d and have attracted attention because of their potential role linking innate and adaptive immune responses. Peripheral NKT cells display a memory‐activated phenotype and can rapidly secrete large amounts of pro‐inflammatory cytokines upon antigenic activation. In this study, we evaluated NKT cells in the context of patients co‐infected with HIV‐1 and Mycobacterium leprae. The volunteers were enrolled into four groups: 22 healthy controls, 23 HIV‐1‐infected patients, 20 patients with leprosy and 17 patients with leprosy and HIV‐1‐infection. Flow cytometry and ELISPOT assays were performed on peripheral blood mononuclear cells. We demonstrated that patients co‐infected with HIV‐1 and M. leprae have significantly lower NKT cell frequencies [median 0.022%, interquartile range (IQR): 0.007–0.051] in the peripheral blood when compared with healthy subjects (median 0.077%, IQR: 0.032–0.405, P < 0.01) or HIV‐1 mono‐infected patients (median 0.072%, IQR: 0.030–0.160, P < 0.05). Also, more NKT cells from co‐infected patients secreted interferon‐γ after stimulation with DimerX, when compared with leprosy mono‐infected patients (P = 0.05). These results suggest that NKT cells are decreased in frequency in HIV‐1 and M. leprae co‐infected patients compared with HIV‐1 mono‐infected patients alone, but are at a more activated state. Innate immunity in human subjects is strongly influenced by their spectrum of chronic infections, and in HIV‐1‐infected subjects, a concurrent mycobacterial infection probably hyper‐activates and lowers circulating NKT cell numbers.
B‐cell receptor: from resting state to activate
Authors: Treanor Bebhinn
Published: January 2012

B‐cell activation is triggered by the binding of antigen to the B‐cell receptor (BCR). The early molecular events triggered by BCR binding of ligand have been well‐characterized both biochemically and using optical microscopy techniques to visualize B‐cell activation as it happens. However, we understand much less about the BCR before activation. For this reason, this review will address recent advances in our view of the structure, organization and dynamics of the resting, unstimulated BCR. These parameters have important implications for our understanding of the initiation of B‐cell activation and will be discussed in the context of current models for BCR activation. These models include the conformation‐induced oligomerization model, in which binding of antigen to monomeric BCR induces a pulling or twisting force causing conformational unmasking of a clustering interface in the Cμ4 domain. Conversely, the dissociation activation model proposes that BCRs exist in auto‐inhibitory oligomers on the resting B‐cell surface and binding of antigen promotes the dissociation of the BCR oligomer exposing phosphorylation residues within Igα/Igβ. Finally, the collision coupling model suggests that BCR are segregated from activating co‐receptors or kinases and activation is associated with changes in BCR mobility on the cell surface, which allows for the functional interaction of these elements.
The development of iron‐free partially stabilized cement for use as dental root‐end filling material
Authors: Ndong F. , Sadhasivam S. , Lin F.‐H. , Savitha S. , Wen‐Hsi W. , Lin C.‐P.
Published: January 2012

Ndong F, Sadhasivam S, Lin F‐H, Savitha S, Wen‐Hsi W, Lin C‐P. The development of iron‐free partially stabilized cement for use as dental root‐end filling material. International Endodontic Journal, 45, 557–564, 2012.

Aim  To determine the effect of increasing the proportion of zinc on partially stabilized cement (PSC) produced using a one‐step sol gel process.

Methodology  A one‐step sol‐gel process of Portland cement‐based PSC with Zn was synthesized by replacing iron nitrate. The crystalline phases of the PSC‐Zn powder were analysed by using X‐ray diffraction (XRD). The experimental groups [i.e. MTA, PSC‐Fe (control), PSC with 1% Zn, PSC with 3% Zn, and PSC with 5% Zn] were immersed in simulated body fluid for 3 h, 1 and 3 days to evaluate the hydration product formation. The microstructure and surface morphology were analysed using scanning electron microscopy (SEM). Initial and final setting times of the materials were determined using an ASTM Vicat needle testing machine. To evaluate the cytotoxicity of PSC‐Zn system, primary osteoblasts cell lines were used.

Results  The addition of increased weight percentages of Zn, resulted in a more unstable phase which favoured the formation of a monoclinic structure of C3S with an increased hydration reaction of PSC and reduced setting time. The cytotoxicity testing of PSC with Zn revealed that the material was not toxic.

Conclusions  The newly synthesized PSC‐Zn material had short setting time and was biocompatible.
Local and landscape management of an expanding range margin under climate change
Authors: Lawson Callum R. , Bennie Jonathan J. , Thomas Chris D. , Hodgson Jenny A. , Wilson Robert J.
Published: January 2012

1. There is a pressing need to understand how to facilitate species’ range shifts under climate change. However, few empirical studies are available to inform decision‐making, particularly at fine spatial and temporal resolutions.

2. We present a case study of a thermally constrained habitat specialist, the silver‐spotted skipper butterflyHesperia comma, at its expanding range margin in south‐eastern Britain. Using data from 724 habitat patches over a 9‐year interval (2000–2009), we examined local and landscape determinants of colonization, survival and population density. We then predicted probabilities of colonization and survival for habitat patches under the observed 1982 and 2009 distributions to investigate how the factors limiting range expansions change through space and time.

3. Between 2000 and 2009,Hesperia commacontinued to expand its range in Britain, but the 67 recorded colonization events were offset by 48 local extinctions. Extinctions were strongly linked to climate, occurring predominantly in cooler regions and on shaded north‐facing slopes.

4. Population density and probability of survival were closely related to conditions within a site, whereas probability of colonization was largely determined by functional connectivity. Survival probability was also influenced by connectivity, suggesting that immigration helped to support extinction‐prone populations (a ‘rescue effect’).

5. Patch occupancy beyond the range margin was primarily constrained by colonization, but close to the expanding front, population survival became the key limiting factor. This pattern was conserved during range expansion, altering management priorities at individual sites.

6. Synthesis and applications. Previous studies on facilitating range shifts have stressed the need to increase landscape‐scale connectivity to remove constraints on colonization, and our data substantiate this advice. However, we show that enhancing population survival can also help to facilitate range expansions, because populations at leading range edges face high extinction risk. Population survival can be improved directly through local management actions, such as enlarging patch size and increasing habitat quality, or indirectly by improving connectivity. Thus, local management can secure vulnerable populations at the range edge and provide larger and more stable migrant sources for future expansion and deserves consideration when facilitating range shifts under climate change.
The ecological impact of oceanic island colonization – a palaeoecological perspective from the Azores
Authors: Connor Simon E. , van Leeuwen Jacqueline F.N. , Rittenour Tammy M. , van der Knaap Willem O. , Ammann Brigitta , Björck Svante
Published: January 2012

Aim  In many cases, human colonization drastically modified the ecosystems of remote oceanic islands before scientists arrived to document the changes. Palaeoecological records before and after human colonization provide insights into the original ecosystems and an assessment of subsequent human impact. We used pollen analysis to compare the impact of 15th century colonization of the Azores with that of natural disturbances such as volcanic eruptions and climate changes.

Location  Azores archipelago, Atlantic Ocean.

Methods  Sediment records from three highland sites in the Azores (on the islands of Pico and Flores) were dated radiometrically and analysed palynologically. Pollen taxa were classified as native, endemic or introduced based on comparison with flora lists. Data were statistically zoned and temporal trends identified using detrended correspondence analysis.

Results  Human colonization of the Azores resulted in rapid, widespread, persistent vegetation changes on a scale unprecedented in the last 2700 years, detectable through the decline of dominant trees, the spread of grasses and fire‐tolerant species, the introduction of exotic plants, evidence for grazing and fire, and changes to soils and moisture availability. During the same period, volcanic eruptions appear to have had more localized impacts on the vegetation, lasting 500–1000 years and favouring endemic taxa. The effect of late Holocene climatic changes on the highland vegetation of the Azores seems to have been minor. Palaeoecological data indicate that at least two plant species went extinct on Pico after human colonization and that some plants regarded as introduced were almost certainly part of the original flora of the islands. Despite a consistent signal of human impact, compositional differences between Juniperus brevifolia communities on Pico and Flores remained after colonization.

Main conclusions  Human colonization had a greater impact on the pristine vegetation of Pico and Flores than climatic changes and volcanic activity during recent millennia. The similarity between post‐colonization changes on the Azores and other oceanic islands suggests a consistent pattern and scale to historical‐era human impact on otherwise pristine ecosystems. These characteristics could be used to further elaborate biogeographical theory and direct conservation efforts towards species that appear most susceptible to human activity.