bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prevention of the β-amyloid peptide-induced inflammatory process by inhibition of double-stranded RNA-dependent protein kinase in primary murine mixed co-cultures
Authors: Couturier J , Paccalin M , Morel M , Terro F , Milin S , Pontcharraud R , Fauconneau B , Page G 
Published: June 2011

AbstractBackgroundInflammation may be involved in the pathogenesis of Alzheimer's disease (AD). There has been little success with anti-inflammatory drugs in AD, while the promise of anti-inflammatory treatment is more evident in experimental models. A new anti-inflammatory strategy requires a better understanding of molecular mechanisms. Among the plethora of signaling pathways activated by β-amyloid (Aβ) peptides, the nuclear factor-kappa B (NF-κB) pathway could be an interesting target. In virus-infected cells, double-stranded RNA-dependent protein kinase (PKR) controls the NF-κB signaling pathway. It is well-known that PKR is activated in AD. This led us to study the effect of a specific inhibitor of PKR on the Aβ42-induced inflammatory response in primary mixed murine co-cultures, allowing interactions between neurons, astrocytes and microglia.MethodsPrimary mixed murine co-cultures were prepared in three steps: a primary culture of astrocytes and microglia for 14 days, then a primary culture of neurons and astrocytes which were cultured with microglia purified from the first culture. Before exposure to Aβ neurotoxicity (72 h), co-cultures were treated with compound C16, a specific inhibitor of PKR. Levels of tumor necrosis factor-α (TNFα), interleukin (IL)-1β, and IL-6 were assessed by ELISA. Levels of PT451-PKR and activation of IκB, NF-κB and caspase-3 were assessed by western blotting. Apoptosis was also followed using annexin V-FITC immunostaining kit. Subcellular distribution of PT451-PKR was assessed by confocal immunofluorescence and morphological structure of cells by scanning electron microscopy. Data were analysed using one-way ANOVA followed by a Newman-Keuls' post hoc testResultsIn these co-cultures, PKR inhibition prevented Aβ42-induced activation of IκB and NF-κB, strongly decreased production and release of tumor necrosis factor (TNFα) and interleukin (IL)-1β, and limited apoptosis.ConclusionIn spite of the complexity of the innate immune response, PKR inhibition could be an interesting anti-inflammatory strategy in AD.
Lymph node-derived donor encephalitogenic CD4+T cells in C57BL/6 mice adoptive transfer experimental autoimmune encephalomyelitis highly express GM-CSF and T-bet
Authors: Cravens Petra D , Hussain Rehana Z , Zacharias Tresa E , Ben Li-Hong , Herndon Emily , Vinnakota Ramya , Lambracht-Washington Doris , Nessler Stefan , Zamvil Scott S , Eagar Todd N , Stüve Olaf 
Published: June 2011

AbstractExperimental autoimmune encephalomyelitis (EAE) is a relevant animal model for the human demyelinating inflammatory disorder of the central nervous system (CNS), multiple sclerosis (MS). Induction of EAE by adoptive transfer allows studying the role of the donor T lymphocyte in disease pathogenesis. It has been challenging to reliably induce adoptive transfer EAE in C57BL/6 (H-2b) mice. The goal of this study was to develop a reproducible and high yield protocol for adoptive transfer EAE in C57BL/6 mice. A step-wise experimental approach permitted us to develop a protocol that resulted in a consistent relatively high disease incidence of ~70% in recipient mice. Donor mice were immunized with myelin oligodendrocyte glycoprotein (MOG)p35-55in complete Freund's adjuvant (CFA) followed by pertussis toxin (PT). Only lymph node cells (LNC) isolated at day 12 post immunization, and restimulatedin vitrofor 72 hours with 10 μg/mL of MOGp35-55and 0.5 ng/mL of interleukin-12 (IL-12) were able to transfer disease. The ability of LNC to transfer disease was associated with the presence of inflammatory infiltrates in the CNS at day 12. Interferon gamma (IFNγ) was produced at comparable levels in cell cultures prepared from mice at both day 6 and day 12 post immunization. By contrast, there was a trend towards a negative association between IL-17 and disease susceptibility in our EAE model. The amount of GM-CSF secreted was significantly increased in the culture supernatants from cells collected at day 12 post immunization versus those collected at day 6 post-immunization. Activated CD4+T cells present in the day 12 LNC cultures maintained expression of the transcription factor T-bet, which has been shown to regulate the expression of the IL-23 receptor. Also, there was an increased prevalence of MOGp35-55-specific CD4+T cells in day 12 LNC afterin vitrore-stimulation. In summary, encephalitogenic LNC that adoptively transfer EAE in C57BL/6 mice were not characterized by a single biomarker in our study, but by a composite of inflammatory markers. Our data further suggest that GM-CSF expression by CD4+T cells regulated by IL-23 contributes to their encephalitogenicity in our EAE model.
The increase of methicillin-resistant Staphylococcus aureus(MRSA) and the presence of an unusual sequence type ST49 in slaughter pigs in Switzerland
Authors: Overesch Gudrun , Büttner Sabina , Rossano Alexandra , Perreten Vincent 
Published: June 2011

Abstract

Background
In years past, methicillin-resistant S. aureus (MRSA) has been frequently detected in pigs in Europe, North America and Asia. Recent, yet sporadic studies have revealed a low occurrence of MRSA in Switzerland. In 2009, a monitoring survey of the prevalence and genetic diversity of methicillin-resistant S. aureus (MRSA) in slaughter pigs in Switzerland was conducted using methods recommended by the EU guidelines, and using a sampling strategy evenly distributed throughout the year and representative of the Swiss slaughter pig population. Monitoring should determine if the overall prevalence of MRSA in the entire country is increasing over the years and if specific multi-resistant MRSA clones are spreading over the country.

Results
In 2009, the nasal cavities of eight out of 405 randomly selected pigs were positive for MRSA, representing a prevalence of 2.0% (95% CI 0.9-3.9). The following year, 23 out of 392 pigs were positive for MRSA [5.9% prevalence (95% CI 3.8-8.7)]. Three multilocus sequence types (ST), four spa types and two types of staphylococcal cassette chromosome mec (SCCmec) elements were detected. The most frequent genotypes were ST398 (MLST)-(spa)t034-V(SCCmec) (n = 18) and ST49-t208-V (n = 7), followed by ST398-t011-V (n = 4), ST398-t1451-V (n = 1), and ST1-t2279-IVc (n = 1). The isolates displayed resistance to ß-lactams [mecA, (31/31); blaZ, (19/31)]; tetracycline [tet(M), (31/31); tet(K), (30/31)] (n = 31); macrolides and lincosamides [erm(C) (4/31) or erm(A) (18/31)] (n = 22); tiamulin [vga(A)v (9/31) or unknown mechanism (18/31)] (n = 27); trimethoprim [dfr(G) (18/31); spectinomycin [ant(9)-Ia (19/31) or unknown mechanism (3/31)] (n = 22); streptomycin [str (19/31)]; sulphamethoxazole (7/31) and ciprofloxacin (n = 1) (mechanisms not determined).

Conclusions
This study is the first to describe the presence of MRSA ST49 in slaughter pigs, and to demonstrate a significant and nearly three-fold increase of MRSA prevalence in pigs within two years. The presence of a specific clonal lineage of MRSA from Switzerland suggests that it has been selected in Swiss pig husbandry. Effective hygiene measures should be enhanced within the entire pig production chain to suppress the spread of these pathogens into the community.
Circulating tumor cells as prognostic and predictive markers in metastatic breast cancer patients receiving first-line systemic treatment
Authors: Giuliano Mario , Giordano Antonio , Jackson Summer , Hess Kenneth R , De Giorgi Ugo , Mego Michal , Handy Beverly C , Ueno Naoto T , Alvarez Ricardo H , De Laurentiis Michelino , De Placido Sabino , Valero Vicente , Hortobagyi Gabriel N , Reuben James M , Cristofanilli Massimo 
Published: June 2011

Abstract
Introduction
Circulating tumor cells (CTCs) represent an independent predictor of outcome in patients with metastatic breast cancer (MBC). We assessed the prognostic impact of CTCs according to different first-line systemic treatments, and explored their potential predictive value in MBC patients.

Methods
We retrospectively evaluated 235 newly diagnosed MBC patients, treated at the University of Texas MD Anderson Cancer Center. All patients had a baseline CTC assessment performed with CellSearch®. Progression-free survival and overall survival were compared with the log-rank test between groups, according to CTC count (< 5 vs. ≥ 5) and type of systemic therapy. We further explored the predictive value of baseline CTCs in patients receiving different treatments.

Results
At a median follow-up of 18 months, the CTC count was confirmed to be a robust prognostic marker in the overall population (median progression-free survival 12.0 and 7.0 months for patients with CTC < 5 and ≥ 5, respectively; P < 0.001). Conversely, in patients with human epidermal growth factor receptor-2-overexpressed/amplified tumors receiving trastuzumab or lapatinib, the baseline CTC count was not prognostic (median progression-free survival 14.5 months for patients with CTC < 5 and 16.1 months for those with CTC ≥ 5; P = 0.947). Furthermore, in patients with human epidermal growth factor receptor-2 normal tumors, a baseline CTC count ≥ 5 identified subjects who derived benefit from more aggressive treatments, including combination chemotherapy and chemotherapy plus bevacizumab.

Conclusions
This analysis suggests that the prognostic information provided by CTC count may be useful in patient stratifications and therapeutic selection, particularly in the group with positive CTCs, in which various therapeutic choices may procure differential palliative benefit.
The Art in Gastronomy: A Modernist Perspective
Authors: myhrvold nathan 
Published: June 2011

In the twentieth century, Modernism swept through virtually every form of art and design—except cuisine. In painting, dance, architecture, literature, and nearly every other form of intellectual creative expression, the continual rejection of the old in favor of new, avant-garde styles became, as Renato Poggioli observed, “the typical chronic condition.” But it was not until the 1970s that Nouvelle Cuisine began to transform classical French cooking, and Nouvelle was a rather limited revolution, narrow in its focus on techniques and ingredients, and limited as well in its impact on Spanish and Italian cuisine.
A true Modernist revolution in food has begun only recently, as chefs such as Ferran Adrià began consciously developing gastronomic experiences that transform meals into dialogues between chef and diner. Avant-garde cooking emphasizes novel, unconventional presentation of familiar flavor themes—the “deconstruction” of the meal by evoking diners’ memories of past meals while taking the dishes in novel directions. A meal at elBulli or other Modernist restaurants often exposes conventions that guests do not even realize exist until the innovative food violates them. Like other good art, Modernist cuisine is challenging and provocative.
Dozens of chefs around the world are now advancing this culinary movement as it follows a trajectory that is similar, in many ways, to the Modernist transformations of other cultural disciplines. Like those predecessor movements, Modernist cuisine has faced some resistance and criticism. But it has arrived.
A Fair Punishment for Humbert Humbert: Strict Liability and Affirmative Defenses
Authors: Bergelson Vera 
Published: June 2011

In this article, I focused on the intersection of strict liability offenses and affirmative defenses. I sought to explore and evaluate a peculiar discrepancy: all states, as well as the Model Penal Code, deny to a defendant charged with a strict liability offense the defense of mistake, yet at the same time, allow most other affirmative defenses. Is this discrepancy warranted? Consider the following scenarios in which Humbert Humbert is charged with the statutory rape of Lolita:
If Humbert Humbert tried to argue that he had acted under a mistaken belief that Lolita was above the age of consent, he most likely would not prevail. He would not prevail even if he made all possible efforts to find out Lolita's true age (e.g., checked Lolita's birth certificate and received a signed sworn affidavit from Lolita's mother) or if he fell prey to Lolita's own deception.
The outcome, however, would be different if Humbert Humbert could prove that his misperception of Lolita's age was a result of insanity. In that case, Humbert Humbert would have a valid defense. He would also have a defense if he could show that he had had sex with Lolita under duress. Say, Clare Quilty, engrossed in the production of his pornographic movie, threatened to beat up Humbert Humbert unless he and Lolita performed a sexual act in front of his camera.
Obviously, the defenses of mistake, insanity, and duress, albeit belonging to the same family of excuses, differ in many important respects. To see whether certain formative differences may account for the different treatment of these defenses, I examine various excuses on the scales of cognitive-volitional, external-internal, and permanent-temporary. In the end, I conclude that, from the moral perspective, there is: (i) no difference between a permanent and temporary impairment; (ii) a marginal difference in favor of external limitation compared to internal; (iii) a meaningful difference in favor of cognitive impairment compared to volitional. Effectively, this conclusion means that a person who commits a strict liability offense pursuant to a reasonable mistake deserves punishment even less than a person who commits the same crime under duress.
I further explore the discrepancy between the treatment of the defense of mistake and other excuses in cases of strict liability from the perspectives of efficiency and other public policies. I conclude that this discrepancy is unwarranted, unfair, and arguably, unconstitutional. Accordingly, I advocate for a revision of the current law and adoption of an across-the-board rule that would make the defense of a reasonable mistake available in any criminal prosecution.
CD14 Modulates Inflammation-Driven Insulin Resistance
Authors: Fernández-Real José Manuel , Pérez del Pulgar Sofia , Luche Elodie , Moreno-Navarrete José Maria , Waget Aurelie , Serino Matteo , Sorianello Eleonora , Sánchez-Pla Alex , Pontaque Francesc Carmona , Vendrell Joan , Chacón Matilde R. , Ricart Wifredo , Burcelin Remy , Zorzano Antonio 
Published: June 2011

OBJECTIVE
The study objective was to evaluate the possible role of the macrophage molecule CD14 in insulin resistance.

RESEARCH DESIGN AND METHODS
The effects of recombinant human soluble CD14 (rh-sCD14) on insulin sensitivity (clamp procedure) and adipose tissue gene expression were evaluated in wild-type (WT) mice, high fat–fed mice, ob/ob mice, and CD14 knockout (KO) mice. We also studied WT mice grafted with bone marrow stem cells from WT donor mice and CD14 KO mice. Finally, CD14 was evaluated in human adipose tissue and during differentiation of human preadipocytes.

RESULTS
rh-sCD14 led to increased insulin action in WT mice, high-fat–fed mice, and ob/ob mice, but not in CD14 KO mice, in parallel to a marked change in the expression of 3,479 genes in adipose tissue. The changes in gene families related to lipid metabolism were most remarkable. WT mice grafted with bone marrow stem cells from WT donor mice became insulin resistant after a high-fat diet. Conversely, WT mice grafted with cells from CD14 KO mice resisted the occurrence of insulin resistance in parallel to decreased mesenteric adipose tissue inflammatory gene expression. Glucose intolerance did not worsen in CD14 KO mice grafted with bone marrow stem cells from high fat–fed WT mice when compared with recipient KO mice grafted with cells from CD14 KO donor mice. CD14 gene expression was increased in whole adipose tissue and adipocytes from obese humans and further increased after tumor necrosis factor-α.

CONCLUSIONS
CD14 modulates adipose tissue inflammatory activity and insulin resistance.
Polychlorinated Biphenyls and Organochlorine Pesticides in Plasma Predict Development of Type 2 Diabetes in the Elderly
Authors: Lee Duk-Hee , Lind P. Monica , Jacobs David R. , Salihovic Samira , van Bavel Bert , Lind Lars 
Published: June 2011

OBJECTIVE
Persistent organic pollutants (POPs), lipophilic chemicals that accumulate mainly in adipose tissue, have recently been linked to type 2 diabetes. However, evidence from prospective studies is sparse. This study was performed to evaluate prospective associations of type 2 diabetes with selected POPs among the elderly.

RESEARCH DESIGN AND METHODS
Nineteen POPs (14 polychlorinated biphenyl [PCB] congeners, 3 organochlorine pesticides, 1 brominated diphenyl ether, and 1 dioxin) were measured in plasma collected at baseline in 725 participants, aged 70 years, of the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS).

RESULTS
After adjusting for known type 2 diabetes risk factors, including obesity, odds ratios (ORs) (95% CIs) for type 2 diabetes at age 75 years (n = 36) according to the quintiles of a summary measure of concentrations of PCBs (vs. the lowest quintile) were 4.5, 5.1, 8.8 (1.8–42.7), and 7.5 (1.4–38.8) (Ptrend &lt;0.01). Among organochlorine pesticides, adjusted ORs across concentrations of trans-nonachlor showed that Ptrend = 0.03. Adjusted ORs (95% CIs) across quintiles of the sum of three organochlorine pesticides were 1.1, 1.6, 1.5, and 3.4 (1.0–11.7) (Ptrend = 0.03). Neither brominated diphenyl ether 47 nor dioxin was significantly associated with incident diabetes. The sum of PCBs improved reclassification significantly when added to traditional risk factors for diabetes.

CONCLUSIONS
Despite the small number of incident cases, this study found that environmental exposure to some POPs substantially increased risk of future type 2 diabetes in an elderly population.
Comparison of Two-Step Versus Four-Step Composite Finishing/Polishing Disc Systems: Evaluation of a New Two-Step Composite Polishing Disc System
Authors: da Costa JB , Goncalves F , Ferracane JL 
Published: June 2011

Clinical Relevance
The two-step composite disc finishing/polishing system, Enhance Flex NST, can provide a nearly equivalent surface finish as two four-step systems on a variety of composites, in approximately half the time. All systems produce clinically acceptable gloss and surface roughness.
Prediction models in cancer care
Authors: Vickers Andrew J. 
Published: June 2011

AbstractPrediction is ubiquitous across the spectrum of cancer care from screening to hospice. Indeed, oncology is often primarily a prediction problem; many of the early stage cancers cause no symptoms, and treatment is recommended because of a prediction that tumor progression would ultimately threaten a patient's quality of life or survival. Recent years have seen attempts to formalize risk prediction in cancer care. In place of qualitative and implicit prediction algorithms, such as cancer stage, researchers have developed statistical prediction tools that provide a quantitative estimate of the probability of a specific event for an individual patient. Prediction models generally have greater accuracy than reliance on stage or risk groupings, can incorporate novel predictors such as genomic data, and can be used more rationally to make treatment decisions. Several prediction models are now widely used in clinical practice, including the Gail model for breast cancer incidence or the Adjuvant! Online prediction model for breast cancer recurrence. Given the burgeoning complexity of diagnostic and prognostic information, there is simply no realistic alternative to incorporating multiple variables into a single prediction model. As such, the question should not be whether but how prediction models should be used to aid decision‐making. Key issues will be integration of models into the electronic health record and more careful evaluation of models, particularly with respect to their effects on clinical outcomes. CA Cancer J Clin 2011. © 2011 American Cancer Society, Inc.
Pollination and protection against herbivory of Nepalese Coelogyninae (Orchidaceae)
Authors: Subedi Abishkar , Chaudhary Ram P. , van Achterberg Cees , Heijerman Theodoor , Lens Frederic , Van Dooren Tom J. M. , Gravendeel Barbara 
Published: June 2011

• Premise of the Study: Although many species in the orchid genus Coelogyne are horticulturally popular, hardly anything is known about their pollination. Pollinators of three species were observed in the field in Nepal. This information is urgently needed because many orchid species in Nepal are endangered. Whether the exudates produced by extrafloral nectaries played a role in protection against herbivory was also investigated.• Methods: Pollinators of C. flaccida, C. nitida, and Otochilus albus were filmed, captured, and identified. Ant surveys and exclusion experiments were carried out. To investigate whether pollinators are needed for fruit set, plants were wrapped in mesh wire bags. Inflorescence stems were examined with microscopy. Fehling's reagent was used to detect sugars in extrafloral exudates.• Key Results: Coelogyne flaccida and C. nitida need pollinators to set fruit and are pollinated by wild bees identified as Apis cerana. Otochilus albus was found to be pollinated by Bombus kashmirensis. Extrafloral nectar was found to be exuded by nectary‐modified stomata and contained high amounts of sugars. Different species of ants were observed collecting these exudates. A significant difference was found in damage inflicted by flower and leaf‐eating beetles between C. nitida plants living in trees with ant nests and those in ant‐free trees.• Conclusions: Floral syndromes include scented and colored trap flowers without reward to their pollinators. All orchids investigated exude extrafloral nectar by nectary‐modified stomata. This nectar was found to flow from the phloem to the stomata through intercellular spaces in the outer parenchymatous layer of the inflorescence.
Leaf fossils of the ancient Tasmanian relict Microcachrys (Podocarpaceae) from New Zealand
Authors: Carpenter Raymond J. , Jordan Gregory J. , Mildenhall Dallas C. , Lee Daphne E. 
Published: June 2011

• Premise of the study: Microcachrys tetragona (Podocarpaceae), endemic to the mountains of Tasmania, represents the only remaining taxon of one of the world's most ancient and widely distributed conifer lineages. Remarkably, however, despite its ∼150 Myr heritage, our understanding of the fossil history of this lineage is based almost entirely on the pollen record. Fossils of Microcachrys are especially important in light of recent molecular phylogenetic and dating evidence. This evidence dates the Microcachrys lineage to the Mesozoic and does not support the traditional placement of Microcachrys as sister to the southeastern Australian genus Pherosphaera.• Methods: We undertook comparative studies of the foliage architecture, cuticle, and paleoecology of newly discovered fossils from the Oligo‐Miocene of New Zealand and M. tetragona and discussed the importance of Microcachrys in the context of Podocarpaceae phylogeny.• Key results: The fossils represent the oldest and first extra‐Australian macrofossils of Microcachrys and are described as the new foliage species M. novae‐zelandiae. These fossils confirm that the distinctive opposite decussate phyllotaxy of the genus is at least as old as the Oligo‐Miocene and contribute to evidence that Microcachrys plants were sometimes important components of oligotrophic swampy habitats.• Conclusions: Leaf fossils of Microcachrys closely comparable with the only extant species confirm that this lineage had a much wider past distribution. The fossil record and recent molecular phylogenetic studies, including that of Microcachrys, also serve to emphasize the important status of Tasmania as a refugium for seed plant lineages.