bluuebunny/crossref_metadata_2025 huggingface dataset:
α
V
β
3
-integrin routes herpes simplex virus to an entry pathway dependent on cholesterol-rich lipid rafts and dynamin2
Authors: Gianni Tatiana , Gatta Valentina , Campadelli-Fiume Gabriella
Published: December 2010

HSVs enter cells in a receptor-dependent [nectin1 or herpesviruses entry mediator (HVEM)] fashion by fusion of the viral envelope with plasma membrane (neutral pH compartment), by endocytosis into neutral or acidic compartments, or by macropinocytosis/phagocytosis. The cellular determinants of the route of entry are unknown. Here, we asked what cellular factors determine the pathway of HSV entry. CHO cells lack β
3
-integrin and the respective α-subunits’ heterodimers. We report that, in the absence of α
V
β
3
-integrin, HSV enters CHO-nectin1 cells through a pathway independent of cholesterol-rich rafts and dynamin2. In the presence of α
V
β
3
-integrin, HSV enters CHO-nectin1 cells through a pathway dependent on cholesterol-rich rafts and dynamin2. HSV enters J-nectin1 and 293T cells through a neutral compartment independent of cholesterol-rich rafts and dynamin2. α
V
β
3
-integrin overexpression in these cells modifies the route of entry to an acidic compartment dependent on cholesterol-rich rafts and dynamin2, hence similar to that in α
V
β
3
-integrin–positive CHO-nectin1 cells. In some cells, the diversion of entry from an integrin- and raft-independent pathway to an acidic compartment requiring cholesterol-rich lipids rafts and dynamin2 is irreversible. Indeed, HSV cannot infect CHO-nectin1-α
V
β
3
cells through any compartment when the αvβ3-integrin–dependent pathway is blocked by anti-integrin antibody, anti-dynamin2, or anti-acidification drugs. We conclude that the αvβ3-integrin is a determinant in the choice of HSV entry pathway into cells. Because the pathway dictated by αvβ3-integrin is through lipid rafts, the platforms for a number of Toll-like receptors, current findings raise the possibility that αvβ3-integrin acts as a sentinel of innate immunity.
Consciousness of subjective time in the brain
Authors: Nyberg Lars , Kim Alice S. N. , Habib Reza , Levine Brian , Tulving Endel
Published: December 2010

“Mental time travel” refers to conscious experience of remembering the personal past and imagining the personal future. Little is known about its neural correlates. Here, using functional magnetic resonance imaging, we explored the hypothesis that mental time travel into “nonpresent” times (past and future) is enabled by a special conscious state (chronesthesia). Well-trained subjects repeatedly imagined taking one and the same short walk in a familiar environment, doing so either in the imagined past, present, or future. In an additional condition, they recollected an instance in which they actually performed the same short walk in the same familiar setting. This design allowed us to measure brain activity correlated with “pure” conscious states of different moments of subjective time. The results showed that the left lateral parietal cortex was differentially activated by nonpresent subjective times compared with the present (past and future > present). A similar pattern was observed in the left frontal cortex, cerebellum, and thalamus. There was no evidence that the hippocampal region is involved in subjective time travel. These findings provide support for theoretical ideas concerning chronesthesia and mental time travel.
The Ino80 chromatin-remodeling complex restores chromatin structure during UV DNA damage repair
Authors: Sarkar Sovan , Kiely Rhian , McHugh Peter J.
Published: December 2010

Chromatin structure is modulated during deoxyribonucleic acid excision repair, but how this is achieved is unclear. Loss of the yeast Ino80 chromatin-remodeling complex (Ino80-C) moderately sensitizes cells to ultraviolet (UV) light. In this paper, we show that INO80 acts in the same genetic pathway as nucleotide excision repair (NER) and that the Ino80-C contributes to efficient UV photoproduct removal in a region of high nucleosome occupancy. Moreover, Ino80 interacts with the early NER damage recognition complex Rad4–Rad23 and is recruited to chromatin by Rad4 in a UV damage–dependent manner. Using a modified chromatin immunoprecipitation assay, we find that chromatin disruption during UV lesion repair is normal, whereas the restoration of nucleosome structure is defective in ino80 mutant cells. Collectively, our work suggests that Ino80 is recruited to sites of UV lesion repair through interactions with the NER apparatus and is required for the restoration of chromatin structure after repair.
CDK5RAP2 stimulates microtubule nucleation by the γ-tubulin ring complex
Authors: Choi Yuk-Kwan , Liu Pengfei , Sze Siu Kwan , Dai Chao , Qi Robert Z.
Published: December 2010

CDK5RAP2 is a human microcephaly protein that contains a γ-tubulin complex (γ-TuC)–binding domain conserved in Drosophila melanogaster centrosomin and Schizosaccharomyces pombe Mto1p and Pcp1p, which are γ-TuC–tethering proteins. In this study, we show that this domain within CDK5RAP2 associates with the γ-tubulin ring complex (γ-TuRC) to stimulate its microtubule-nucleating activity and is therefore referred to as the γ-TuRC–mediated nucleation activator (γ-TuNA). γ-TuNA but not its γ-TuC–binding-deficient mutant stimulates microtubule nucleation by purified γ-TuRC in vitro and induces extensive, γ-TuRC-dependent nucleation of microtubules in a microtubule regrowth assay. γ-TuRC bound to γ-TuNA contains NME7, FAM128A/B, and actin in addition to γ-tubulin and GCP2–6. RNA interference–mediated depletion of CDK5RAP2 impairs both centrosomal and acentrosomal microtubule nucleation, although γ-TuRC assembly is unaffected. Collectively, these results suggest that the γ-TuNA found in CDK5RAP2 has regulatory functions in γ-TuRC–mediated microtubule nucleation.
Rseg—an R package to optimize segmentation of SNP array data
Authors: Lamy Philippe , Wiuf Carsten , Ørntoft Torben F. , Andersen Claus L.
Published: December 2010

Summary: The use of high-density SNP arrays for investigating copy number alterations in clinical tumor samples, with intra tumor heterogeneity and varying degrees of normal cell contamination, imposes several problems for commonly used segmentation algorithms. This calls for flexibility when setting thresholds for calling gains and losses. In addition, sample normalization can induce artifacts in the copy-number ratios for the non-changed genomic elements in the tumor samples.

Results: We present an open source R package, Rseg, which allows the user to define sample-specific thresholds to call gains and losses. It also allows the user to correct for normalization artifacts.

Availability: The R package, Rseg, is available at: http://www.cs.au.dk/~plamy/Rseg/ and runs on Linux and MS-Windows.

Contact:  plamy@cs.au.dk

Supplementary information:  Supplementary data are available at Bioinformatics online.
Acute Appendicitis
Authors: Takhar Arunjit S. , Patel Meera , Al-Taan Omer , Stephenson James A.
Published: December 2010

The term ‘appendicitis’ was first described by Reginald H. Fitz in 1886 and has since become the most common surgical emergency that can affect people of any age. Appendicitis is usually a clinical diagnosis so it is important for GPs to have a good understanding of the symptoms and signs of appendicitis in order to differentiate it from other causes of lower abdominal pain. GPs can play an invaluable role in the outcome of this condition as early referral can result in timely surgical intervention that leads to reduced morbidity.
Oxford Handbook of Infectious Diseases and Microbiology
Authors: Torok Estee , Moran Ed , Cooke Fiona
Published: December 2010

This Handbook takes an integrated approach to both infectious disease and microbiology. Referenced to national frameworks and current legislation, it covers the basic principles of bacteriology and virology, specific information on diseases and conditions, and material on 'hot topics' such as bioterrorism and preventative medicine.
Perspectives on Remorin Proteins, Membrane Rafts, and Their Role During Plant–Microbe Interactions
Authors: Jarsch Iris K. , Ott Thomas
Published: December 2010

Invasion of host cells by pathogenic or mutualistic microbes requires complex molecular dialogues that often determine host survival. Although several components of the underlying signaling cascades have recently been identified and characterized, our understanding of proteins that facilitate signal transduction or assemble signaling complexes is rather sparse. Our knowledge of plant-specific remorin proteins, annotated as proteins with unknown function, has recently advanced with respect to their involvement in host–microbe interactions. Current data demonstrating that a remorin protein restricts viral movement in tomato leaves and the importance of a symbiosis-specific remorin for bacterial infection of root nodules suggest that these proteins may serve such regulatory functions. Direct interactions of other remorins with a resistance protein in Arabidopsis thaliana, and differential phosphorylation upon perception of microbial-associated molecular patterns and during expression of bacterial effector proteins, strongly underline their roles in plant defense. Furthermore, the specific subcellular localization of remorins in plasma membrane microdomains now provides the opportunity to visualize membrane rafts in living plants cells. There, remorins may oligomerize and act as scaffold proteins during early signaling events. This review summarizes current knowledge of this protein family and the potential roles of remorins in membrane rafts.
Analysis of a Prophage Gene Frequency Revealed Population Variation of ‘Candidatus Liberibacter asiaticus’ from Two Citrus-Growing Provinces in China
Authors: Liu Rui , Zhang Pei , Pu Xuelian , Xing Xiaoqian , Chen Jianchi , Deng Xiaoling
Published: December 2010

Prophages are important genetic elements of bacterial genomes and are involved in lateral gene transfer, pathogenicity, environmental adaptations, and interstrain genetic variability. In this study, the sequence of a prophage terminase gene of ‘Candidatus Liberibacter asiaticus’, a bacterium associated with citrus Huanglongbing (HLB), was selected as a molecular marker to assess the genetic variation in two ‘Ca. L. asiaticus’ populations from geographically distinct provinces (Guangdong and Yunnan) in China. The frequency of the prophage terminase gene was 15.8% (19/120) in Guangdong (altitude <500 m) and 97.4% (38/39) in Yunnan (altitude >2,000 m). The difference was highly significant (P < 0.0001) based on χ2 analysis. However, the partial prophage terminase gene sequences obtained from 10 Guangdong strains and 6 Yunnan strains were identical or highly similar, suggesting that at least some bacterial strains in the two locations shared a common recent origin. This is the first report on population variation of ‘Ca. L. asiaticus’ in China, where HLB was first described. The population variation of ‘Ca. L. asiaticus’ in the two geographical regions and the related HLB epidemiology were discussed.
Effectiveness of Kasugamycin Against Erwinia amylovora and its Potential Use for Managing Fire Blight of Pear
Authors: Adaskaveg J. E. , Förster H. , Wade M. L.
Published: December 2010

Comparative field studies on the management of fire blight were conducted in California on Asian and Bartlett pear using single-bactericide, mixture, and rotation treatments of selected compounds. Treatment efficacy was evaluated based on the natural occurrence of the disease or after inoculation with Erwinia amylovora. Kasugamycin at 100 mg/liter demonstrated similar or higher pre- and post-infection activity than the industry standards, streptomycin and oxytetracycline. Phytotoxicity caused by kasugamycin was observed only when five or six sequential weekly applications were done. In a six-spray rotation program including three bactericides (copper, kasugamycin, and oxytetracycline), with each being used twice, phytotoxicity was minor. Baseline sensitivity concentrations for kasugamycin were established for growth of 376 isolates of E. amylovora from California. Values for the lowest concentration where a reduction in growth on nutrient agar was observed ranged from 3.5 to 18.3 mg/liter, with a mean value of 8.7 mg/liter. Values for ≥95% inhibition of growth ranged from 6.9 to 46.7 mg/liter, with a mean value of 18.5 mg/liter. These inhibitory values for kasugamycin were higher than those for streptomycin or oxytetracycline. The in vitro activity of all three compounds was highly dependent on the agar medium used in the sensitivity assay. The activity of kasugamycin was also highly dependent on the pH of the medium and was significantly higher at pH 5.1 than pH 7.3. With the planned registration in the United States, kasugamycin represents the first new, highly effective bactericide for managing fire blight in over 40 years.
Potent in vitro and in vivo antitumor effects of MDM2 inhibitor nutlin‐3 in gastric cancer cells
Authors: Endo Shinji , Yamato Kenji , Hirai Sachiko , Moriwaki Toshikazu , Fukuda Kuniaki , Suzuki Hideo , Abei Masato , Nakagawa Ichiro , Hyodo Ichinosuke
Published: December 2010

The tumor suppressor gene p53 is the most frequently mutated gene in human cancers. However, its mutation rate is relatively low in gastric cancer compared with other cancers. In this study, we investigated the mechanisms underlying the antitumor effects of nutlin‐3, an inhibitor of human homolog of murine double minute 2 (MDM2). MDM2 is a negative regulator of p53. Four gastric cancer cell lines with wild‐type p53 (wt p53) and three with mutant‐type p53 (mt p53) were analyzed for MDM2 and MDM4 expression by immunoblotting, and for their gene amplification by quantitative real‐time PCR. Moreover, the viability of cells exposed to nutlin‐3 was examined by WST‐8 assay, and the expression of p53 and its downstream genes was analyzed by immunoblotting. Nutlin‐3 stabilized p53 and increased the expression of p21WAF1 and Noxa, and cleaved poly (ADP)‐ribose polymerase regardless of the pre‐expression levels of MDM2 and MDM4 in gastric cancer cells with wt p53. Flow cytometry revealed that nutlin‐3 arrested the cell cycle in G1 phase and induced apoptosis in the cell lines. These nutlin‐3 effects were not observed in the cell lines with mt p53. Nutlin‐3 exerted additive or synergistic cytotoxicity in combination with 5‐fluorouracil or cisplatin in most cell lines with wt p53. An in vivo antitumor effect of nutlin‐3 alone and its additive augmentation by 5‐fluorouracil were confirmed in an MDM2 overexpressed xenograft tumor model. Nutlin‐3 showed potent antitumor activity against human gastric cancer cells with wt p53 and shows promise as a single agent and in combination with conventional anticancer drugs. (Cancer Sci 2011; 102: 605–613)
Review article: specifically targeted anti‐viral therapy for hepatitis C – a new era in therapy
Authors: Lange C. M. , Sarrazin C. , Zeuzem S.
Published: December 2010

Aliment Pharmacol Ther 2010; 32: 14–28

Background  Novel, directly acting anti‐viral agents, also named ‘specifically targeted anti‐viral therapy for hepatitis C’ (STAT‐C) compounds, are currently under development.

Aim  To review the potential of STAT‐C agents which are currently under clinical development, with a focus on agents that target HCV proteins.

Methods  Studies evaluating STAT‐C compounds were identified by systematic literature search using PubMed as well as databases of abstracts presented in English at recent liver and gastroenterology congresses.

Results  Numerous directly‐acting anti‐viral agents are currently under clinical phase I–III evaluation. Final results of phase II clinical trials evaluating the most advanced compounds telaprevir and boceprevir indicate that the addition of these NS3/4A protease inhibitors to pegylated interferon‐alfa and ribavirin strongly improves the chance to achieve a SVR in treatment‐naive HCV genotype 1 patient as well as in prior nonresponders and relapsers to standard therapy. Monotherapy with directly acting anti‐virals is not suitable. NS5B polymerase inhibitors in general have a lower anti‐viral efficacy than protease inhibitors.

Conclusions  STAT‐C compounds in addition to pegylated interferon‐alfa and ribavirin can improve SVR rates at least in HCV genotype 1 patients. Future research needs to evaluate whether a SVR can be achieved by combination therapies of STAT‐C compounds in interferon‐free regimens.
CcpA‐mediated repression of Clostridium difficile toxin gene expression
Authors: Antunes Ana , Martin‐Verstraete Isabelle , Dupuy Bruno
Published: December 2010

The presence of glucose or other rapidly metabolizable carbon sources in the bacterial growth medium strongly represses Clostridium difficile toxin synthesis independently of strain origin. In Gram‐positive bacteria, carbon catabolite repression (CCR) is generally regarded as a regulatory mechanism that responds to carbohydrate availability. In the C. difficile genome all elements involved in CCR are present. To elucidate in vivo the role of CCR in C. difficile toxin synthesis, we used the ClosTron gene knockout system to construct mutants of strain JIR8094 that were unable to produce the major components of the CCR signal transduction pathway: the phosphotransferase system (PTS) proteins (Enzyme I and HPr), the HPr kinase/phosphorylase (HprK/P) and the catabolite control protein A, CcpA. Inactivation of the ptsI, ptsH and ccpA genes resulted in derepression of toxin gene expression in the presence of glucose, whereas repression of toxin production was still observed in the hprK mutant, indicating that uptake of glucose is required for repression but that phosphorylation of HPr by HprK is not. C. difficile CcpA was found to bind to the regulatory regions of the tcdA and tcdB genes but not through a consensus cre site motif. Moreover in vivo and in vitro results confirmed that HPr‐Ser45‐P does not stimulate CcpA‐dependent binding to DNA targets. However, fructose‐1,6‐biphosphate (FBP) alone did increase CcpA binding affinity in the absence of HPr‐Ser45‐P. These results showed that CcpA represses toxin expression in response to PTS sugar availability, thus linking carbon source utilization to virulence gene expression in C. difficile.
A novel role for a glycosylphosphatidylinositol‐anchored aspartyl protease, CgYps1, in the regulation of pH homeostasis in Candida glabrata
Authors: Bairwa Gaurav , Kaur Rupinder
Published: December 2010

Proteases, key virulence factors of many bacterial and fungal pathogens, are pivotally important for nutrient acquisition, invasion and adherence to host cells and evasion/escape from host immune cells. In this study, we report a novel role for CgYps1, member of a family of 11 GPI‐linked aspartyl proteases, in a human opportunistic fungal pathogen, Candida glabrata, in the regulation of pH homeostasis under acidic environmental conditions. We show that CgYps1 is required to survive low‐external‐pH environment and the inability of Cgyps1Δ mutant to maintain pH homeostasis results in intracellular acidification and increased reactive oxygen species (ROS) production. We also provide evidence that the reduced intracellular pH in Cgyps1Δ mutant under acidic conditions is, partly, owing to the diminished activity of a plasma membrane proton pump, CgPma1, an orthologue of a key component of pH homeostasis machinery in Saccharomyces cerevisiae, Pma1. In addition, we have examined C. glabrata's response to low environmental pH via genome‐wide expression analysis and several genes required for protein folding/modification and stress response pathways including seven of the CgYPS genes were found to be upregulated. Lastly, we show that C. glabrata responds to acidic environment by reducing total β‐glucan levels in the cell wall in a CgYps1‐dependent manner.
Effect of Pre‐freeze Addition of Cysteine Hydrochloride and Reduced Glutathione in Semen of Crossbred Jersey Bulls on Sperm Parameters and Conception Rates
Authors: Perumal P , Selvaraju S , Selvakumar S , Barik AK , Mohanty DN , Das S , Das RK , Mishra PC
Published: December 2010

Contents

This study was aimed to assess the effect of pre‐freeze addition of cysteine hydrochloride and glutathione (GSH) on post‐thaw sperm functional parameters and field fertility. The experimental bulls (n = 6) aged 4–6 years were used for this study. A total of 36 ejaculates (six ejaculates per bull) were collected and divided into three groups, group I (control), group II (5 mmcysteine hydrochloride) and group III (5 mmGSH). The extended semen samples with and without additives were filled in mini straw using automatic filling and sealing machine and cryopreserved in liquid nitrogen. Post‐freeze seminal traits were recorded after thawing at 37°C for 30 s. The curvilinear velocity (VCL) and amplitude of lateral head displacement values were significantly (p < 0.05) higher in GSH than the cysteine and control groups. Post‐thaw plasmalemma integrity was significantly (p < 0.01) higher in GSH group when compared to cysteine and control groups. The loss of acrosomal integrity was significantly (p < 0.01) lower in GSH than in cysteine and control groups. Addition of GSH non‐significantly (p = 0.1) improved mitochondrial membrane potential (MMP) (per cent) than control group. This study indicates that the addition of cysteine and GSH suggestive (p = 0.08) of reducing lipid peroxide levels. The conception rate (%) in glutathione group was significantly (p < 0.05) higher than that in cysteine (68 vs 58) and control (49) groups. The post‐thaw sperm progressive forward motility (r = 0.4) had moderate, but no significant correlation with conception rate. However, post‐thaw straight‐line velocity (r = 0.7), loss of acrosomal integrity (r = −0.8) and MMP (r = 0.9) had significant (p < 0.05) correlation with field fertility. This study indicates that the use of glutathione as semen additive may be used for improving post‐thaw semen quality and overall augmentation of pregnancy in cows.
Two Trebouxia algae with different physiological performances are ever‐present in lichen thalli of Ramalina farinacea. Coexistence versus Competition?
Authors: Casano Leonardo M. , del Campo Eva M. , García‐Breijo Francisco J. , Reig‐Armiñana José , Gasulla Francisco , del Hoyo Alicia , Guéra Alfredo , Barreno Eva
Published: December 2010

Ramalina farinacea is an epiphytic fruticose lichen that is relatively abundant in areas with Mediterranean, subtropical or temperate climates. Little is known about photobiont diversity in different lichen populations. The present study examines the phycobiont composition of several geographically distant populations of R. farinacea from the Iberian Peninsula, Canary Islands and California as well as the physiological performance of isolated phycobionts. Based on anatomical observations and molecular analyses, the coexistence of two different taxa of Trebouxia (working names, TR1 and TR9) was determined within each thallus of R. farinacea in all of the analysed populations. Examination of the effects of temperature and light on growth and photosynthesis indicated a superior performance of TR9 under relatively high temperatures and irradiances while TR1 thrived at moderate temperature and irradiance. Ramalina farinacea thalli apparently represent a specific and selective form of symbiotic association involving the same two Trebouxia phycobionts. Strict preservation of this pattern of algal coexistence is likely favoured by the different and probably complementary ecophysiological responses of each phycobiont, thus facilitating the proliferation of this lichen in a wide range of habitats and geographic areas.
The evolution of pedicellariae in echinoids: an arms race against pests and parasites
Authors: Coppard Simon E. , Kroh Andreas , Smith Andrew B.
Published: December 2010

Coppard, S.E., Kroh, A. and Smith, A.B. (2010). The evolution of pedicellariae in echinoids: an arms race against pests and parasites. —Acta Zoologica (Stockholm) 00:1–24.

Sea urchins (Echinoidea) have evolved a diverse array of jawed appendages termed pedicellariae to deter pests and predators. Pedicellarial structure and function are reviewed and their distribution mapped in 75 extant genera. Using a phylogeny of echinoids at family level constructed from 353 skeletal characters scored across 162 extant and fossil taxa, the evolution of pedicellarial form and function is reconstructed. For much of the Palaeozoic echinoids possessed a very restricted pedicellarial armament. By the early Mesozoic a diverse array of pedicellarial types had become established, implying that the threat from predators and pests markedly increased at this time. Since the Triassic, echinoids have continued to improve their defensive capability by evolving more effective venom delivery in globiferous pedicellariae, developing spatulate‐tips and curved blades for a more efficient grab in tridentate pedicellariae, and stouter, more robust valves with a stronger bite in ophicephalous pedicellariae to disable and remove ectoparasites. However, pedicellarial types are shown to be particularly prone to subsequent secondary loss, especially among infaunal echinoids, and thus have higher homoplasy levels than other phylogenetically useful skeletal structures.
Maintaining Legitimacy: Controversies, Orders of Worth, and Public Justifications
Authors: Patriotta Gerardo , Gond Jean‐Pascal , Schultz Friederike
Published: December 2010

abstract

We build on Boltanski and Thévenot's theory of justification to account for the ways in which different stakeholder groups actively engage with discourses and objects to maintain the legitimacy of institutions that are relevant to their activity. We use this framework to analyse a controversy emerging from a nuclear accident which involved a large European energy company and sparked public debate on the legitimacy of nuclear power. Based on the findings, we elaborate a process model of institutional repair that explains the role of agents and the structural constraints they face in attempting to maintain legitimacy. The model enhances institutional understandings of legitimacy maintenance in three main respects: it proposes a view of legitimacy maintenance as a controversy‐based process progressing through stakeholders' justifications vis‐à‐vis a public audience; it demonstrates the role of meta‐level ‘orders of worth’ as multiple modalities for agreement which shape stakeholders' public justifications during controversies; and it highlights the capacities that stakeholders deploy in developing robust justifications out of a plurality of forms of agreement.
WHAKAPAPA, GENEALOGY AND GENETICS
Authors: EVANS DONALD
Published: December 2010

This paper provides part of an analysis of the use of the Maori term whakapapa in a study designed to test the compatibility and commensurability of views of members of the indigenous culture of New Zealand with other views of genetic technologies extant in the country. It is concerned with the narrow sense of whakapapa as denoting biological ancestry, leaving the wider sense of whakapapa as denoting cultural identity for discussion elsewhere. The phenomenon of genetic curiosity is employed to facilitate this comparison. Four levels of curiosity are identified, in the Maori data, which penetrate more or less deeply into the psyche of individuals, affecting their health and wellbeing. These phenomena are compared with non‐Maori experiences and considerable commonalities are discovered together with a point of marked difference. The results raise important questions for the ethical application of genetic technologies.
BUOYS FOR ECCENTRIC EXISTENCE
Authors: BUCKLEY JAMES J.
Published: December 2010

David Kelsey's Eccentric Existence argues that what we need is a “systematically unsystematic” account of human existence, a set of “buoys” or non‐negotiable convictions articulated on the basis of canonical Scriptures, leaving abundant room for philosophers and other non‐theologians to make their contributions. Embodied persons themselves/ourselves are constituted in three irreducibly complex canonically biblical narratives as creatures, reconciled, and consummated—although it is not always clear what aspects of these narratives are “buoys” and which are more negotiable. The God who constitutes embodied persons is the triune God of Nicaea (like a triple helix) who operates as one but in irreducibly distinct ways as Father and Son and Spirit—and cannot be mere instrument of human purposes. Kelsey intentionally leaves a number of Trinitarian and Christological questions open for further treatment, creating remarkable challenges for traditionalists and modernists alike.
Humanitarian Aid, Fertility and Economic Growth
Authors: NEANIDIS KYRIAKOS C.
Published: December 2010

This paper examines the effect of humanitarian aid on fertility and economic growth. In an overlapping generations model, where health status in adulthood depends on health in childhood, adult agents allocate their time to work, leisure and childrearing activities. Humanitarian aid influences the probability of survival to adulthood, health in childhood, and the time that adults allocate to childrearing, giving rise to an ambiguous effect on both fertility and growth. An empirical investigation for the period 1973–2007 suggests that humanitarian aid has on average a zero effect on the rates of fertility and of per capita output growth.
The relevance of iron in the pathogenesis of Parkinson’s disease
Authors: Sian‐Hülsmann Jeswinder , Mandel Silvia , Youdim Moussa B. H. , Riederer Peter
Published: December 2010

J. Neurochem. (2011) 118, 939–957.

Alterations of iron levels in the brain has been observed and documented in a number of neurodegenerative disorders including Parkinson’s disease (PD). The elevated nigral iron levels observed in PD may reflect a dysfunction of brain iron homeostasis. Under normal physiological conditions excess iron can be sequestrated in ferritin and neuromelanin. Alternatively, the excess iron may represent a component of brain iron deposition associated with ageing. The aetiology of idiopathic PD largely remains an enigma. However, intensive investigations have provided a host of putative mechanisms that might contribute to the pathogenesis underlying the characteristic degeneration of the dopaminergic neurons in the substantia nigra (SN). The mechanisms proposed include oxidative (and nitrative) stress, inflammation, excitotoxicity, mitochondrial dysfunction, altered proteolysis and finally apoptotic induced cell death. Iron‐mediated cellular destruction is mediated primarily via reactive oxygen or/and nitrogen species induced oxidative stress. Furthermore, these pathogenic mechanisms appear to be closely interlinked to the cascade of events leading to cellular death. There are conflicting reports about the stage during disease progression at which nigral iron change occurs in PD. Some have found that there are no changes in iron content SN in asymptomatic incidental Lewy body disease, suggesting it may represent a secondary event in the cascade of neuronal degeneration. In contrast, others have found an elevation of iron in SN in pre‐clinical stages. These discrepancies may be attributed to the occurrence of different sub‐groups of the disease. This concurs with the notion that PD represents a group of related diseases with a number of potential pathogenic pathways.
Genital Ulcers as an Unusual Sign of Periodic Fever, Aphthous Stomatitis, Pharyngotonsillitis, Cervical Adenopathy Syndrome: A Novel Symptom?
Authors: Lin Chien‐Ming , Wang Chih‐Chien , Lai Chi‐Chieh , Fan Hueng‐Chuen , Huang Wei‐Hsuan , Cheng Shin‐Nan
Published: December 2010

Abstract:  Periodic fever, aphthous stomatitis, pharyngotonsillitis, cervical adenopathy (PFAPA) syndrome, which is characterized by periodic episodes of high fever, aphthous stomatitis, pharyngitis, and cervical adenitis, is of unknown etiology and manifests usually before 5 years of age. A patient with periodic fever, aphthous stomatitis, pharyngotonsillitis, cervical adenopathy syndrome simultaneously presenting with genital ulcers has not been reported previously. We describe a 12‐year‐old Chinese girl with a 2‐year history of periodic fever, aphthous stomatitis, pharyngotonsillitis, cervical adenopathy syndrome who exhibited vulvar ulcers accompanying an episode of febrile periodic fever, aphthous stomatitis, pharyngotonsillitis, and cervical adenopathy. Although during a 1‐year follow‐up this girl did not manifest typical symptoms/signs of Behçet’s disease except recurrent oral aphthae and genital ulcers, it is possible that periodic fever, aphthous stomatitis, pharyngotonsillitis, cervical adenopathy syndrome and Behçet’s disease could have overlapping manifestations. Furthermore, this report would add to the evidence of a wide variation in the clinical symptomatology of PFAPA syndrome.
Malignant Atrophic Papulosis: A Case Report with Severe Visual and Neurological Impairment
Authors: Gutiérrez‐Pascual Marta , Hernández‐Martín Angela , Colmenero Isabel , García‐Peñas Juan José , López‐Pino Miguel Angel , Torrelo Antonio
Published: December 2010

Abstract:  Malignant atrophic papulosis, or Degos’ disease, is a severe systemic vasculopathy extremely rare in children. The skin, gastrointestinal tract, and central nervous system are most frequently affected. We report a 5‐year‐old girl with malignant atrophic papulosis who presented with widespread skin lesions from early infancy and severe visual and neurological impairment.
Wells’ Syndrome Presenting as a Noninfectious Bullous Cellulitis in a Child
Authors: SHAMS MARISSA , HUDGENS JEANNETTE , LESHER JACK L. , FLORENTINO FRANCES
Published: December 2010

Abstract:  Wells’ syndrome is a rare disease that is even more uncommon in childhood. This case report illustrates the potential devastating extent of the disease and highlights the unusual presentation of bullae in a child. It is imperative to consider Wells’ syndrome in patients with presumed cellulitis and eosinophilia who fail to respond to antibiotics.
Sorghum Insect Problems and ManagementF
Authors: Guo Chunshan , Cui Wei , Feng Xue , Zhao Jianzhou , Lu Guihua
Published: December 2010

Sorghum (Sorghum bicolor) has high levels of starch, sugar, and fiber and is one of the most important energy crops in the world. Insect damage is one of the challenges that impacts sorghum biomass production. There are at least 150 insect species that can infest sorghum varieties worldwide. These insects can complete several generations within a growing season, they target various parts of sorghum plants at developmental stages, and they cause significant biomass losses. Genetic research has revealed the existence of resistant genetics in sorghum and insect tolerant sorghum varieties have been identified. Various control methods have been developed, yet more effective management is needed for increasing sorghum biomass production. Although there are no transgenic sorghum products on the market yet, biotechnology has been recognized as an important tool for controlling insect pests and increasing sorghum production.
N‐Phosphinyl Imine Chemistry (I): Design and Synthesis of Novel N‐Phosphinyl Imines and their Application to Asymmetric aza‐Henry Reaction
Authors: Pindi Suresh , Kaur Parminder , Shakya Gaurav , Li Guigen
Published: December 2010

Novel chiral N‐phosphinamide and N‐phosphinyl imines have been designed, synthesized and applied to asymmetric aza‐Henry reaction to give excellent chemical yields (92%– quant.) and diastereoselectivity (91% to >99%de). The reaction showed a great substrate scope in which aromatic/aliphatic aldehyde‐ and ketone‐derived N‐phosphinyl imines can be employed as electrophiles. The chiral N‐phosphinamide can be stored at room temperature for more than 2 months without inert gas protection, and chiral N‐phosphinyl imines were also proven to be highly stable at room temperature for a long period under inert gas protection. The N‐phosphinyl group enabled the product purification to be performed simply by washing crude product with EtOAc and hexane. This reaction joined other eight GAP (Group‐Assistant‐Purification) chemistry processes that were developed in our laboratories. The absolute configuration has been unambiguously determined by converting a β‐nitroamine product into a known N‐Boc sample.
Know Your Standard: Clarifying the CIE Erythema Action Spectrum
Authors: Webb Ann R. , Slaper Harry , Koepke Peter , Schmalwieser Alois W.
Published: December 2010

The standard erythema action spectrum provides an internationally accepted representation of the erythema‐inducing effectiveness of wavelengths in the UV part of the spectrum. The action spectrum forms the basis of the UV index used for public health information, defines the standard erythema dose unit and the minimum erythema dose and is the default response spectrum aspired to by a range of UV radiometer manufacturers. However, there are several versions of this erythema action spectrum in use, and only one of them has been endorsed as a standard. While the differences in erythemally weighted radiation incurred by choice of action spectrum will be no more than a few percent, this uncertainty is unnecessary. Here we detail the differences in the different versions of erythema action spectra, illustrate the resulting effects in quantifying UV doses and encourage readers to use only the standard version of the action spectrum in the future.
Dental implant tourism
Authors: Barrowman RA , Grubor D , Chandu A
Published: December 2010

Access and affordability of dental care can be problematic for some in the Australian community. Therefore, dental tourism is increasingly becoming more attractive to some patients due to decreased expense, increased convenience and immediacy of treatment. However, there are significant issues for both clinician and patient in regards to dental tourism. Lack of accountability and regulation are the main issues and this is particularly evident when complications occur. This paper presents five cases where complications have arisen in the setting of dental tourism.
Role of glycogen availability in sarcoplasmic reticulum Ca2+ kinetics in human skeletal muscle
Authors: Ørtenblad Niels , Nielsen Joachim , Saltin Bengt , Holmberg Hans‐Christer
Published: December 2010

Non‐technical summary

Glucose is stored as glycogen in skeletal muscle. The importance of glycogen as a fuel during exercise has been recognized since the 1960s; however, little is known about the precise mechanism that relates skeletal muscle glycogen to muscle fatigue. We show that low muscle glycogen is associated with an impairment of muscle ability to release Ca2+, which is an important signal in the muscle activation. Thus, depletion of glycogen during prolonged, exhausting exercise may contribute to muscle fatigue by causing decreased Ca2+ release inside the muscle. These data provide indications of a signal that links energy utilization, i.e. muscle contraction, with the energy content in the muscle, thereby inhibiting a detrimental depletion of the muscle energy store.
Skeletal muscle fatigue precedes the slow component of oxygen uptake kinetics during exercise in humans
Authors: Cannon Daniel T. , White Ailish C. , Andriano Melina F. , Kolkhorst Fred W. , Rossiter Harry B.
Published: December 2010

Non‐technical summary

The mechanisms determining exercise intolerance are poorly understood. A reduction in work efficiency in the form of an additional energy cost and oxygen requirement occurs during high‐intensity exercise and contributes to exercise limitation. Muscle fatigue and subsequent recruitment of poorly efficient muscle fibres has been proposed to mediate this decline. These data demonstrate in humans, that muscle fatigue, generated in the initial minutes of exercise, is correlated with the increasing energy demands of high‐intensity exercise. Surprisingly, however, while muscle fatigue reached a plateau, oxygen uptake continued to increase throughout 8 min of exercise. This suggests that additional recruitment of inefficient muscle fibres may not be the sole mechanism contributing to the decline in work efficiency during high‐intensity exercise.
Modulation of hippocampal stratum lacunosum‐moleculare microcircuits
Authors: Maccaferri Gianmaria
Published: December 2010

Abstract  Although the rigorous anatomical definition of the microcircuitry of the brain is essential for understanding its functions, the modulation of the physiological properties of neurons and synapses may confer an additional level of complexity. Here, I review two examples of neuromodulation within a specific microcircuit of the hippocampus, i.e. the local network of stratum lacunosum‐moleculare. In particular, I will examine the actions of two different types of neuromodulators on the excitability and electrical coupling of two specific classes of cells. First, I will review the effects of noradrenaline on GABAergic networks. Particular emphasis will be placed on neurogliaform cells. Then, I will describe the chemokinergic modulation of spontaneous firing of Cajal–Retzius cells, mediated by the chemokine (C‐X‐C motif) ligand 12/stromal cell‐derived factor‐1 α (CXCL12/SDF‐1) via the CXC chemokine receptor 4 (CXCR4). The complexities created by these diverse types of modulations for network activity, together with their potential implications for stratum lacunosum‐moleculare processing of information in vivo, will be also presented and briefly discussed.
TRPM2: a multifunctional ion channel for calcium signalling
Authors: Sumoza‐Toledo Adriana , Penner Reinhold
Published: December 2010

The transient potential receptor melastatin‐2 (TRPM2) channel has emerged as an important Ca2+ signalling mechanism in a variety of cells, contributing to cellular functions that include cytokine production, insulin release, cell motility and cell death. Its ability to respond to reactive oxygen species has made TRPM2 a potential therapeutic target for chronic inflammation, neurodegenerative diseases, and oxidative stress‐related pathologies. TRPM2 is a non‐selective, calcium (Ca2+)‐permeable cation channel of the melastatin‐related transient receptor potential (TRPM) ion channel subfamily. It is activated by intracellular adenosine diphosphate ribose (ADPR) through a diphosphoribose hydrolase domain in its C‐terminus and regulated through a variety of factors, including synergistic facilitation by [Ca2+]i, cyclic ADPR, H2O2, NAADP, and negative feedback regulation by AMP and permeating protons (pH). In addition to its role mediating Ca2+ influx into the cells, TRPM2 can also function as a lysosomal Ca2+ release channel, contributing to cell death. The physiological and pathophysiological context of ROS‐mediated events makes TRPM2 a promising target for the development of therapeutic tools of inflammatory and degenerative diseases.
Application of a Navier–Stokes Solver to the Study of Open Rotor Aerodynamics
Authors: Zachariadis Alexios , Hall Cesare A.
Published: December 2010

This paper establishes a proven computational approach for open rotor configurations that can be used as a basis for further studies involving open rotor aerodynamics and design. Many of the difficulties encountered in the application of computational fluid dynamics to an open rotor engine arise due to the removal of the casing that is present in conventional aero-engine turbomachinery. In this work, an advanced three-dimensional Navier–Stokes solver is applied to the open rotor. The approach needed to accurately capture the aerodynamics is investigated with particular attention to the mesh configuration and the specification of the boundary conditions. A new three-step meshing strategy for generating the mesh and the most suitable type of far-field boundary condition are discussed. A control volume analysis approach is proposed for post-processing the numerical results for the rotor performance. The capabilities of the solver and the applied methodology are demonstrated at both cruise and take-off operating conditions. The comparison of the computational results with the experimental measurements shows good agreement for both data trend and magnitudes.
A Kinase-Independent Role for Unoccupied Insulin and IGF-1 Receptors in the Control of Apoptosis
Authors: Boucher Jeremie , Macotela Yazmin , Bezy Olivier , Mori Marcelo A. , Kriauciunas Kristina , Kahn C. Ronald
Published: December 2010

Cells lacking both insulin and IGF-1 receptors are resistant to apoptosis.
The Yin and Yang of Plant Caspases
Authors: Hines Pamela J.
Published: December 2010

An ancient link between cell death control and innate immune receptor function has been discovered in plants.
Science Signaling
Podcast: 7 December 2010
Authors: Huang Lan , VanHook Annalisa M.
Published: December 2010

Oxidative stress induces separation of the catalytic and regulatory portions of the yeast 26
S
proteasome, enabling the catalytic core to degrade toxic oxidized proteins.
Comparative Effects of Carbapenems on Bacterial Load and Host Immune Response in aKlebsiella pneumoniaeMurine Pneumonia Model
Authors: Hilliard Jamese J. , Melton John L. , Hall LeRoy , Abbanat Darren , Fernandez Jeffrey , Ward Christine K. , Bunting Rachel A. , Barron A. , Lynch A. Simon , Flamm Robert K.
Published: December 2010

Doripenem is a carbapenem with potent broad-spectrum activity against Gram-negative pathogens, including antibiotic-resistantEnterobacteriaceae. As the incidence of extended-spectrum β-lactamase (ESBL)-producing Gram-negative bacilli is increasing, it was of interest to examine thein vivocomparative efficacy of doripenem, imipenem, and meropenem against aKlebsiella pneumoniaeisolate expressing the TEM-26 ESBL enzyme. In a murine lethal lower respiratory infection model, doripenem reduced theKlebsiellalung burden by 2 log10CFU/g lung tissue over the first 48 h of the infection. Treatment of mice with meropenem or imipenem yielded reductions of approximately 1.5 log10CFU/g during this time period. Seven days postinfection,Klebsiellatiters in the lungs of treated mice decreased an additional 2 log10CFU/g relative to those in the lungs of untreated control animals. Lipopolysaccharide (LPS) endotoxin release assays indicated that 6 h postinfection, meropenem- and imipenem-treated animals had 10-fold more endotoxin in lung homogenates and sera than doripenem-treated mice. Following doripenem treatment, the maximum endotoxin release postinfection (6 h) was 53,000 endotoxin units (EU)/ml, which was 2.7- and 6-fold lower than imipenem or meropenem-treated animals, respectively. While the levels of several proinflammatory cytokines increased in both the lungs and sera following intranasalK. pneumoniaeinoculation, doripenem treatment, but not meropenem or imipenem treatment, resulted in significantly increased interleukin 6 levels in lung homogenates relative to those in lung homogenates of untreated controls, which may contribute to enhanced neutrophil killing of bacteria in the lung. Histological examination of tissue sections indicated less overall inflammation and tissue damage in doripenem-treated mice, consistent with improved antibacterial efficacy, reduced LPS endotoxin release, and the observed cytokine induction profile.