bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mathematical model reveals how regulating the three phases of T‐cell response could counteract immune evasion
Authors: Lorenzi Tommaso , Chisholm Rebecca H. , Melensi Matteo , Lorz Alexander , Delitala Marcello 
Published: June 2015

SummaryT cells are key players in immune action against the invasion of target cells expressing non‐self antigens. During an immune response, antigen‐specific T cells dynamically sculpt the antigenic distribution of target cells, and target cells concurrently shape the host's repertoire of antigen‐specific T cells. The succession of these reciprocal selective sweeps can result in ‘chase‐and‐escape’ dynamics and lead to immune evasion. It has been proposed that immune evasion can be countered by immunotherapy strategies aimed at regulating the three phases of the immune response orchestrated by antigen‐specific T cells: expansion, contraction and memory. Here, we test this hypothesis with a mathematical model that considers the immune response as a selection contest between T cells and target cells. The outcomes of our model suggest that shortening the duration of the contraction phase and stabilizing as many T cells as possible inside the long‐lived memory reservoir, using dual immunotherapies based on the cytokines interleukin‐7 and/or interleukin‐15 in combination with molecular factors that can keep the immunomodulatory action of these interleukins under control, should be an important focus of future immunotherapy research.
H‐ficolin binds Aspergillus fumigatus leading to activation of the lectin complement pathway and modulation of lung epithelial immune responses
Authors: Bidula Stefan , Sexton Darren W. , Yates Matthew , Abdolrasouli Alireza , Shah Anand , Wallis Russell , Reed Anna , Armstrong‐James Darius , Schelenz Silke 
Published: July 2015

SummaryAspergillus fumigatus is an opportunistic fungal pathogen that typically infects the lungs of immunocompromised patients leading to a high mortality. H‐Ficolin, an innate immune opsonin, is produced by type II alveolar epithelial cells and could participate in lung defences against infections. Here, we used the human type II alveolar epithelial cell line, A549, to determine the involvement of H‐ficolin in fungal defence. Additionally, we investigated the presence of H‐ficolin in bronchoalveolar lavage fluid from transplant patients during pneumonia. H‐Ficolin exhibited demonstrable binding to A. fumigatus conidia via l‐fucose, d‐mannose and N‐acetylglucosamine residues in a calcium‐ and pH‐dependent manner. Moreover, recognition led to lectin complement pathway activation and enhanced fungal association with A549 cells. Following recognition, H‐ficolin opsonization manifested an increase in interleukin‐8 production from A549 cells, which involved activation of the intracellular signalling pathways mitogen‐activated protein kinase MAPK kinase 1/2, p38 MAPK and c‐Jun N‐terminal kinase. Finally, H‐ficolin concentrations were significantly higher in bronchoalveolar lavage fluid of patients with lung infections compared with control subjects (n = 16; P = 0·00726). Receiver operating characteristics curve analysis further highlighted the potential of H‐ficolin as a diagnostic marker for lung infection (area under the curve = 0·77; P < 0·0001). Hence, H‐ficolin participates in A. fumigatus defence through the activation of the lectin complement pathway, enhanced fungus–host interactions and modulated immune responses.
How mechanisms of habitat preference evolve and promote divergence with gene flow
Authors: Berner D. , Thibert‐Plante X. 
Published: June 2015

AbstractHabitat preference may promote adaptive divergence and speciation, yet the conditions under which this is likely are insufficiently explored. We use individual‐based simulations to study the evolution and consequence of habitat preference during divergence with gene flow, considering four different underlying genetically based behavioural mechanisms: natal habitat imprinting, phenotype‐dependent, competition‐dependent and direct genetic habitat preference. We find that the evolution of habitat preference generally requires initially high dispersal, is facilitated by asymmetry in population sizes between habitats, and is hindered by an increasing number of underlying genetic loci. Moreover, the probability of habitat preference to emerge and promote divergence differs greatly among the underlying mechanisms. Natal habitat imprinting evolves most easily and can allow full divergence in parameter ranges where no divergence is possible in the absence of habitat preference. The reason is that imprinting represents a one‐allele mechanism of assortative mating linking dispersal behaviour very effectively to local selection. At the other extreme, direct genetic habitat preference, a two‐allele mechanism, evolves under restricted conditions only, and even then facilitates divergence weakly. Overall, our results indicate that habitat preference can be a strong reproductive barrier promoting divergence with gene flow, but that this is highly contingent on the underlying preference mechanism.
Humidity affects populations of Drosophila suzukii (Diptera: Drosophilidae) in blueberry
Authors: Tochen S. , Woltz J. M. , Dalton D. T. , Lee J. C. , Wiman N. G. , Walton V. M. 
Published: July 2015

AbstractTemperature and humidity affect insect physiology, survival, fecundity, reproductive status and behaviour. Complementing previous work investigating the effects of temperature on adult survival and fecundity of the invasive frugivorous pest, Drosophila suzukii (Matsumura), this study was conducted to determine the effect of humidity on D. suzukii larval development, adult survival, fecundity and reproductive status using blueberry as a host substrate. The five constant humidity levels in laboratory bioassays were 20, 33, 71, 82 and 94% RH at 20.6 ± 0.2°C. As RH increased, fecundity and longevity increased. At the higher humidity levels, RH had limited impact on mean generation times (T), larval development and eclosion times. The highest net reproductive rate (Ro = 68) and highest intrinsic rate of population increase (rm = 0.17) were both recorded at 94% RH. The reproductive status of females, as indicated by the number of mature oocytes per female, was significantly greater at 82 and 94% RH, compared to 71% RH. In addition to the laboratory procedures, we correlated field trap captures over an 81‐day summer period to relative humidity (RH) levels in close proximity to those traps. In the field, low ambient humidity levels resulted in decreased trap captures. A humidity‐dependent population model predicted lower densities of D. suzukii relative to populations at higher humidity. This study supports the hypothesis that cultural practices that minimize lower humidity levels in crops can contribute to the management of D. suzukii. Such methods may include open pruning, drip irrigation and field floor management.
Efficacy of Some Essential Oil Components as Food Preservatives Against Food Contaminating Molds, Aflatoxin B1 Production and Free Radical Generation
Authors: Prakash Bhanu , Mishra Prashant Kumar , Kedia Akash , Dwivedy Abhishek Kumar , Dubey N.K. 
Published: July 2015

AbstractThis study explores the efficacy of essential oil components, viz. Z‐citral, E‐citral, methyl cinnamate and fenchone individually and in combination (1:1:1:1), against food contaminating molds, aflatoxin B1 production and as antioxidant. The oil components (except fenchone) and their combination inhibited the aflatoxigenic strain of Aspergillus flavus (LHP‐10) and 13 additional food‐infesting molds at minimum inhibitory concentration ranging between 0.50 and 5.25 μL/mL while aflatoxin production inhibited between 0.6 and 2.50 μL/mL. Methyl cinnamate showed the highest antifungal and anti‐aflatoxigenic activity followed by the combination, Z‐citral, E‐citral and fenchone. The oil components exhibited synergistic action during antioxidant activity as the oil combination was substantially superior (IC50 value 5.89 μL/mL) to the sum of the individual antioxidant effects. The antifungal mechanism of action of components and their combination was studied by measuring the ergosterol content in the plasma membrane of mold species. During in vivo experiments in storage containers, the oil combination provided >50% protection of chickpea samples against fungal infestation up to 6 months of storage without affecting their viability.Practical ApplicationsBased on the results of the present investigation, some essential oil components and their combination may be recommended as plant‐based preservatives in view of their antifungal activity against food‐infesting molds, aflatoxin secretion and as antioxidant. The efficacy of the components in protecting the fungal contamination of chickpea samples during storage condition without affecting their viability strengthens their formulation for practical application. The study recommends some essential oil components to food and agri‐industries as safer alternatives of synthetic preservatives in view of their adverse effects on consumer's health and environment.
Daytime Physical Activity and Sleep in Hospitalized Older Adults: Association with Demographic Characteristics and Disease Severity
Authors: Beveridge Claire , Knutson Kristen , Spampinato Lisa , Flores Andrea , Meltzer David O. , Van Cauter Eve , Arora Vineet M. 
Published: July 2015

ObjectivesTo assess objectively measured daytime physical activity and sleep duration and efficiency in hospitalized older adults and explore associations with demographic characteristics and disease severity.DesignProspective cohort study.SettingUniversity of Chicago Medical Center general medicine wards.ParticipantsCommunity‐dwelling inpatients aged 50 and older (N = 120)MeasurementsPhysical activity and sleep were measured using wrist accelerometers. Information on Charlson Comorbidity Index and length of stay was collected from charts. Random‐effects linear regression analysis was used to examine the association between in‐hospital sleep and physical activity.ResultsFrom March 2010 to May 2013, 120 participants wore wrist actigraphy monitors for at least 2 nights and 1 intervening day. Median activity level over the waking period was 77 counts/min (interquartile range 51–121 counts/min), an activity level that approximately corresponds to sitting while watching television (65 counts/min). Mean sleep duration the night before the activity interval was 289 ± 157 minutes, and mean sleep efficiency the night before the activity interval was 65.2 ± 26.9%. Mean activity counts/min were lowest for the oldest participants (oldest quartile 62, 95% confidence interval (CI) = 50–75; youngest quartile 121, 95% CI = 98–145, trend test P < .001) and those with highest Charlson Comorbidity Index (highest tertile 71, 95% CI = 60–83; lowest tertile 125, 95% CI = 104–147, trend test P = .01). Controlling for severity of illness and demographic characteristics, activity declined by 3 counts/min (95% CI = −5.65 to −0.43, P = .02) for each additional hour of inpatient sleep.ConclusionOlder, sicker adults are less physically active during hospitalization. In contrast to studies in the community, inpatients who slept more were not more active. This may highlight that need for sleep is greater in the hospital than in the community.
Chandipura virus perturbs cholesterol homeostasis leading to neuronal apoptosis
Authors: Ghosh Sourish , Mukherjee Sriparna , Basu Anirban 
Published: June 2015

AbstractChandipura virus (CHPV; genus Vesiculovirus, family Rhabdoviridae) induces neuronal death through the Fas‐mediated extrinsic apoptosis pathway. What propels this apoptosis remains unclear, although oxysterols have been reported to be key players in neurodegeneration. In our study of CHPV‐infected brain samples, we observed over‐expression of genes such as apolipoprotein E, Cyp46a1, Srebf‐1 and Nsdhl. This backs up the hypothesis that CHPV replication demands cholesterol that is supplied by apolipoprotein E through low density lipid receptors, lipid metabolism being pivotal for viral replication. We were able to illustrate this with over‐expression of low density lipid receptors in CHPV‐infected neurons. An upsurge of cholesterol concentration has been observed in neurons, triggering the expression of Cyp46a1 enzyme and culminating into the conversion of cholesterol to 24(S)‐hydroxycholesterol. Increased 24(S)‐hydroxycholesterol concentration is toxic to neurons, propelling neuronal apoptosis through the Fas‐mediated extrinsic apoptosis pathway. For the first time, perturbation of cholesterol homeostasis in brain is shown to be utilized by the viruses for both maturation and the release of its matured virions outside the cells for continuous neuropathogenesis.
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Chandipura virus (CHPV) increases cholesterol import through low density lipid (LDL) receptor in neurons. Cholesterol in neurons are utilized to form the CHPV envelope. Excessive accumulation of cholesterol gets converted to 24(S)‐hydroxycholesterol (24(S)‐OHC) by cholesterol 24‐hydroxylase enzyme (encoded by Cyp46a1 gene) that induces neuronal death through apoptosis. Therapeutics aimed against cholesterol homeostasis perturbation may be an effective anti‐viral strategy.
SorCS1 variants and amyloid precursor protein (APP) are co‐transported in neurons but only SorCS1c modulates anterograde APP transport
Authors: Hermey Guido , Schmidt Nadine , Bluhm Björn , Mensching Daniel , Ostermann Kristina , Rupp Carsten , Kuhl Dietmar , Kins Stefan 
Published: June 2015

AbstractProcessing of amyloid precursor protein (APP) into amyloid‐β peptide (Aβ) is crucial for the development of Alzheimer's disease (AD). Because this processing is highly dependent on its intracellular itinerary, altered subcellular targeting of APP is thought to directly affect the degree to which Aβ is generated. The sorting receptor SorCS1 has been genetically linked to AD, but the underlying molecular mechanisms are poorly understood. We analyze two SorCS1 variants; one, SorCS1c, conveys internalization of surface‐bound ligands whereas the other, SorCS1b, does not. In agreement with previous studies, we demonstrate co‐immunoprecipitation and co‐localization of both SorCS1 variants with APP. Our results suggest that SorCS1c and APP are internalized independently, although they mostly share a common post‐endocytic pathway. We introduce functional Venus‐tagged constructs to study SorCS1b and SorCS1c in living cells. Both variants are transported by fast anterograde axonal transport machinery and about 30% of anterograde APP‐positive transport vesicles contain SorCS1. Co‐expression of SorCS1b caused no change of APP transport kinetics, but SorCS1c reduced the anterograde transport rate of APP and increased the number of APP‐positive stationary vesicles. These data suggest that SorCS1 and APP share trafficking pathways and that SorCS1c can retain APP from insertion into anterograde transport vesicles.image
Altered APP trafficking is thought to modulate its processing. SorCS1 has been suggested to function in APP trafficking. We analyzed if the two SorCS1 variants, SorCS1b and SorCS1c, tie APP to the cell surface or modify its internalization and intracellular targeting. We observed co‐localization and vesicular co‐transport of APP and SorCS1, but independent internalization and sorting through a common post‐endocytic pathway. Co‐expression of one variant, SorCS1c, reduced anterograde APP transport. These data demonstrate that SorCS1 and APP share trafficking pathways and that SorCS1c can retain APP from insertion into anterograde transport vesicles.
Mu opioid receptor activation enhances regulator of G protein signaling 4 association with the mu opioid receptor/G protein complex in a GTP‐dependent manner
Authors: Santhappan Rema , Crowder Alicia Tamara , Gouty Shawn , Cox Brian M. , Côté Thomas E. 
Published: June 2015

AbstractThe interaction of Regulator of G protein Signaling 4 (RGS4) with the rat mu opioid receptor (MOR)/G protein complex was investigated. Solubilized MOR from rat brain membranes was immunoprecipitated in the presence of RGS4 with antibodies against the N‐terminus of MOR (anti‐MOR10–70). Activation of MOR with [D‐Ala2, N‐Me‐Phe4, Gly5‐ol] enkephalin (DAMGO) during immunoprecipitation caused a 150% increase in Goα and a 50% increase in RGS4 in the pellet. When 10 μM GTP was included with DAMGO, there was an additional 72% increase in RGS4 co‐immunoprecipitating with MOR (p = 0.003). Guanosine 5′‐O‐(3‐thiotriphosphate) (GTPγS) increased the amount of co‐precipitating RGS4 by 93% (compared to DAMGO alone, p = 0.008), and the inclusion of GTPγS caused the ratio of MOR to RGS4 to be 1 : 1 (31 fmoles : 28 fmoles, respectively). GTPγS also increased the association of endogenous RGS4 with MOR. In His6RGS4/Ni2+‐NTA agarose pull down experiments, 0.3 μM GTPγS tripled the binding of Goα to His6RGS4, whereas the addition of 100 μM GDP blocked this effect. Importantly, activation of solubilized MOR with DAMGO in the presence of 100 μM GDP and 0.3 μM GTPγS increased Goα binding to His6RGS4/Ni2+‐NTA agarose (p = 0.001).
imageRegulators of G protein Signaling (RGS) shorten the time that G proteins are active. Activation of the mu opioid receptor (MOR) causes GTP to bind to and to activate Go (αoβγ). RGS4 then binds to the activated αo‐GTP/MOR complex and accelerates the intrinsic GTPase of αo. After αo dissociates from MOR, RGS4 remains bound to the C‐terminal region of MOR.
Serum WFA+‐M2BP levels as a prognostic factor in patients with early hepatocellular carcinoma undergoing curative resection
Authors: Toyoda Hidenori , Kumada Takashi , Tada Toshifumi , Kaneoka Yuji , Maeda Atsuyuki , Korenaga Masaaki , Mizokami Masashi , Narimatsu Hisashi 
Published: July 2015

AbstractBackground & AimsSerum tumour markers for hepatocellular carcinoma (HCC) have less prognostic significance in early stage. Serum Wisteria floribunda agglutinin‐positive Mac‐2‐binding protein (WFA+‐M2BP) levels are reportedly associated with hepatocarcinogenic potential in patients with chronic liver diseases. We investigated the prognostic significance of pretreatment serum WFA+‐M2BP levels in patients with early‐stage HCC.MethodsA total of 240 patients who underwent hepatic resection for naïve Barcelona Clinic Liver Cancer (BCLC) class 0 or A HCC were analysed. WFA+‐M2BP and tumour markers for HCC were measured from serum obtained just prior to treatment. Post‐operative recurrence and survival rates were compared according to these serum markers, tumour stage and Child–Pugh class.ResultsThere was an association between serum WFA+‐M2BP levels and the fibrosis grade of resected noncancerous liver tissue, whereas no association was found between WFA+‐M2BP levels and tumour progression or liver function. In a multivariate analysis, pretreatment serum WFA+‐M2BP level was associated with recurrence and survival, respectively, independent of HCC progression or fibrosis grade of resected noncancerous liver tissue. Recurrence rates after hepatic resection were significantly higher in patients with a pretreatment serum WFA+‐M2BP ≥ 3.00 than those with a pretreatment serum WFA+‐M2BP < 3.00 (P = 0.0038). Survival rates were lower in patients with a pretreatment serum WFA+‐M2BP ≥ 3.00 than those with a pretreatment serum WFA+‐M2BP < 3.00 (P = 0.0187).ConclusionsSerum WFA+‐M2BP level is a prognostic factor for recurrence and survival, in addition to tumour progression and liver function, in patients with early‐stage HCC treated with curative hepatic resection.
Lack of genetic diversity across diverse immune genes in an endangered mammal, the Tasmanian devil (Sarcophilus harrisii)
Authors: Morris Katrina M. , Wright Belinda , Grueber Catherine E. , Hogg Carolyn , Belov Katherine 
Published: June 2015

AbstractThe Tasmanian devil (Sarcophilus harrisii) is threatened with extinction due to the spread of devil facial tumour disease. Polymorphisms in immune genes can provide adaptive potential to resist diseases. Previous studies in diversity at immune loci in wild species have almost exclusively focused on genes of the major histocompatibility complex (MHC); however, these genes only account for a fraction of immune gene diversity. Devils lack diversity at functionally important immunity loci, including MHC and Toll‐like receptor genes. Whether there are polymorphisms at devil immune genes outside these two families is unknown. Here, we identify polymorphisms in a wide range of key immune genes, and develop assays to type single nucleotide polymorphisms (SNPs) within a subset of these genes. A total of 167 immune genes were examined, including cytokines, chemokines and natural killer cell receptors. Using genome‐level data from ten devils, SNPs within coding regions, introns and 10 kb flanking genes of interest were identified. We found low polymorphism across 167 immune genes examined bioinformatically using whole‐genome data. From this data, we developed long amplicon assays to target nine genes. These amplicons were sequenced in 29–220 devils and found to contain 78 SNPs, including eight SNPS within exons. Despite the extreme paucity of genetic diversity within these genes, signatures of balancing selection were exhibited by one chemokine gene, suggesting that remaining diversity may hold adaptive potential. The low functional diversity may leave devils highly vulnerable to infectious disease, and therefore, monitoring and preserving remaining diversity will be critical for the long‐term management of this species. Examining genetic variation in diverse immune genes should be a priority for threatened wildlife species. This study can act as a model for broad‐scale immunogenetic diversity analysis in threatened species.
Immunogenetic heterogeneity in a widespread ungulate: the European roe deer (Capreolus capreolus)
Authors: Quéméré Erwan , Galan Maxime , Cosson Jean‐François , Klein François , Aulagnier Stéphane , Gilot‐Fromont Emmanuelle , Merlet Joël , Bonhomme Maxime , Hewison A. J. Mark , Charbonnel Nathalie 
Published: June 2015

AbstractUnderstanding how immune genetic variation is shaped by selective and neutral processes in wild populations is of prime importance in both evolutionary biology and epidemiology. The European roe deer (Capreolus capreolus) has considerably expanded its distribution range these last decades, notably by colonizing agricultural landscapes. This range shift is likely to have led to bottlenecks and increased roe deer exposure to a new range of pathogens that until recently predominantly infected humans and domestic fauna. We therefore investigated the historical and contemporary forces that have shaped variability in a panel of genes involved in innate and acquired immunity in roe deer, including Mhc‐Drb and genes encoding cytokines or toll‐like receptors (TLRs). Together, our results suggest that genetic drift is the main contemporary evolutionary force shaping immunogenetic variation within populations. However, in contrast to the classical view, we found that some innate immune genes involved in micropathogen recognition (e.g. Tlrs) continue to evolve dynamically in roe deer in response to pathogen‐mediated positive selection. Most studied Tlrs (Tlr2, Tlr4 and Tlr5) had similarly high levels of amino acid diversity in the three studied populations including one recently established in southwestern France that showed a clear signature of genetic bottleneck. Tlr2 implicated in the recognition of Gram‐positive bacteria in domestic ungulates, showed strong evidence of balancing selection. The high immunogenetic variation revealed here implies that roe deer are able to cope with a wide spectrum of pathogens and to respond rapidly to emerging infectious diseases.