bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficacy of the EZ-IO® needle driver for out-of-hospital intraosseous access - a preliminary, observational, multicenter study
Authors: Schalk Richard , Schweigkofler Uwe , Lotz Gösta , Zacharowski Kai , Latasch Leo , Byhahn Christian 
Published: October 2011

Abstract

Background
Intraosseous (IO) access represents a reliable alternative to intravenous vascular access and is explicitly recommended in the current guidelines of the European Resuscitation Council when intravenous access is difficult or impossible. We therefore aimed to study the efficacy of the intraosseous needle driver EZ-IO® in the prehospital setting.

Methods
During a 24-month period, all cases of prehospital IO access using the EZ-IO® needle driver within three operational areas of emergency medical services were prospectively recorded by a standardized questionnaire that needed to be filled out by the rescuer immediately after the mission and sent to the primary investigator. We determined the rate of successful insertion of the IO needle, the time required, immediate procedure-related complications, the level of previous experience with IO access, and operator's subjective satisfaction with the device.

Results
77 IO needle insertions were performed in 69 adults and five infants and children by emergency physicians (n = 72 applications) and paramedics (n = 5 applications). Needle placement was successful at the first attempt in all but 2 adults (one patient with unrecognized total knee arthroplasty, one case of needle obstruction after placement). The majority of users (92%) were relative novices with less than five previous IO needle placements. Of 22 responsive patients, 18 reported pain upon fluid administration via the needle. The rescuers' subjective rating regarding handling of the device and ease of needle insertion, as described by means of an analogue scale (0 = entirely unsatisfied, 10 = most satisfied), provided a median score of 10 (range 1-10).

Conclusions
The EZ-IO® needle driver was an efficient alternative to establish immediate out-of-hospital vascular access. However, significant pain upon intramedullary infusion was observed in the majority of responsive patients.
Impact of interleukin-21 in the pathogenesis of primary Sjogren's syndrome: increased serum levels of interleukin-21 and its expression in the labial salivary glands
Authors: Kang Kwi Young , Kim Hyun-Ok , Kwok Seung-Ki , Ju Ji Hyeon , Park Kyung-Su , Sun Dong-Il , Jhun Joo Yeon , Oh Hye Jwa , Park Sung-Hwan , Kim Ho-Youn 
Published: October 2011

Abstract

Introduction

Interleukin (IL)-21 is a cytokine that controls the functional activity of effector T helper cells and the differentiation of Th17 cells, and promotes B-cell differentiation. To test whether IL-21 participates in the pathogenesis of primary Sjögren's syndrome (SS), serum IL-21 level was measured and IL-21 expression in the labial salivary glands (LSG) was examined.

Methods

Serum IL-21 levels in 40 primary SS, 40 rheumatoid arthritis (RA), and 38 systemic lupus erythematosus (SLE) patients and 20 healthy controls were measured. Serum IL-21 levels of SS patients were assessed for correlations with laboratory data, including anti-nuclear antibody, anti-Ro/La antibodies, globulin, immunoglobulin (Ig) class, and IgG subclass. LSGs from 16 primary SS and 4 controls with sicca symptoms were evaluated for IL-21 and IL-21 receptor (IL-21R) expression by immunohistochemistry. Confocal microscopy was performed to further characterize the IL-21 positive cells.

Results

Primary SS patients had significantly higher serum IL-21 levels than controls, and these increments correlated positively with levels of IgG, IgG1. Serum IgG1 levels correlated with anti-Ro antibody titers. Immunohistochemical analyses showed that lymphocytic foci and the periductal area of the LSGs from SS patients expressed high levels of IL-21 and lower levels of IL-21R, whereas the control LSGs showed minimal expression of both antigens. The more the lymphocyte infiltrated, IL-21expression in LSGs showed a tendency to increase. Confocal microscopic analyses revealed that IL-21 expressing infiltrating lymphocytes in the LSGs of SS patients also expressed CXCR5.

Conclusions

Primary SS is associated with high serum IL-21 levels that correlate positively with serum IgG, especially IgG1, levels. The expression of IL-21 is increased as more lymphocytes infiltrated in LSGs. These observations suggest that IL-21 may play an important role in primary SS pathogenesis.
Replacement of E-cadherin by N-cadherin in the mammary gland leads to fibrocystic changes and tumor formation
Authors: Kotb Ahmed M , Hierholzer Andreas , Kemler Rolf 
Published: October 2011

Abstract
Introduction
E-cadherin (E-cad; cadherin 1) and N-cadherin (N-cad; cadherin 2) are the most prominent members of the cadherin family of cell adhesion molecules. Although they share many structural and functional features, they are expressed in an almost mutually exclusive manner in vivo.

Methods
To explore functional differences between the two cadherins in vivo, we recently generated a knock-in line in which N-cad is expressed from the E-cad locus. In combination with a conditional gene inactivation approach, we expressed N-cad in the absence of E-cad (referred to as Ncadk.i.) in alveolar epithelial cells of the mammary gland starting in late pregnancy.

Results
We found that the sole presence of N-cad induces constitutively active fibroblast growth factor (Fgf) signaling and a precocious involution resulting in massive apoptosis of alveolar cells. To block apoptosis, we conditionally deleted one allele of p53 in Ncadk.i. mice and observed a temporal rescue of alveolar morphology and function. However, an accumulation of fibrotic tissue and cysts with increasing age and lactation cycles was observed. This phenotype closely resembled fibrocystic mastopathy (FM), a common disorder in humans, which is thought to precede breast cancer. Concordantly, 55% of Ncadk.i. mice harboring a heterozygous p53 deletion developed malignant and invasive tumors.

Conclusions
Our results demonstrate a possible role for N-cad in the formation of fibrosis and cysts in the mammary gland. Moreover, we show that these lesions precede the development of malignant tumors. Thus, we provide a new mouse model to investigate the molecular mechanisms of fibrocystic mastopathy and the transition from benign to malignant tumors.
Mobilization of hematopoietic stem and leukemia cells
Authors: Schroeder Mark A , DiPersio John F 
Published: October 2011

ABSTRACT
HSC mobilization is an essential homeostatic process during inflammation and for the maintenance of hematopoietic progenitors. It has been exploited for the therapeutic application of HSC transplantation. Recent evidence suggests that leukemic cells share surface molecules in common with stem cells and may be mobilized under similar conditions. This effect could be used for therapeutic interventions. In this review, we will provide evidence showing that leukemia cells and stem cells traffic similarly and may share a common niche. Studies are discussed comparing and contrasting the mechanism of normal stem cells and leukemic cell mobilization through the CXCR4/CXCL12 axis and other key intermediaries.
Fc receptor-like 5 promotes B cell proliferation and drives the development of cells displaying switched isotypes
Authors: Dement-Brown Jessica , Newton Christopher S , Ise Tomoko , Damdinsuren Bazarragchaa , Nagata Satoshi , Tolnay Mate 
Published: October 2011

ABSTRACT
The biological roles of B cell membrane proteins in the FCRL family are enigmatic. FCRL proteins, including FCRL5, were shown to modulate early BCR signaling, although the subsequent, functional consequences of receptor engagement are poorly understood. We found that FCRL5 surface protein itself was induced temporarily upon BCR stimulation of human, naive B cells, indicating precise control over timing of FCRL5 engagement. Cross-linking of FCRL5 on cells induced to express FCRL5 enhanced B cell proliferation significantly. This enhancement required costimulation of the BCR and TLR9, two signals required for optimal proliferation of naive B cells, whereas T cell help in the form of anti-CD40 and IL-2 was dispensable. In addition, we found that FCRL5 stimulation generated a high proportion of cells displaying surface IgG and IgA. Optimal development of cells expressing switched isotypes required T cell help, in addition to stimuli found necessary for enhanced proliferation. Surprisingly, cells that developed upon FCRL5 stimulation simultaneously displayed surface IgM, IgG, and IgA. Cells expressing multiple Ig isotypes were described in hairy cell leukemia, a disease in which FCRL5 is overexpressed. Enhanced proliferation and downstream isotype expression upon FCRL5 stimulation could reflect a physiological role for FCRL5 in the expansion and development of antigen-primed B cells. In addition, FCRL5 may promote growth of malignant cells in hairy cell leukemia and other FCRL5-expressing tumors.
Histone deacetylase inhibition facilitates GM-CSF-mediated expansion of myeloid-derived suppressor cells in vitro and in vivo
Authors: Rosborough Brian R , Castellaneta Antonino , Natarajan Sudha , Thomson Angus W , Turnquist Hēth R 
Published: October 2011

ABSTRACT
Chromatin-modifying HDACi exhibit anti-inflammatory properties that reflect their ability to suppress DC function and enhance regulatory T cells. The influence of HDACi on MDSCs, an emerging regulatory leukocyte population that potently inhibits T cell proliferation, has not been examined. Exposure of GM-CSF-stimulated murine BM cells to HDACi led to a robust expansion of monocytic MDSC (CD11b+Ly6C+F4/80intCD115+), which suppressed allogeneic T cell proliferation in a NOS- and HO-1-dependent manner with similar potency to control MDSCs. The increased yield of MDSCs correlated with blocked differentiation of BM cells and an overall increase in HSPCs (Lin–Sca-1+c-Kit+). In vivo, TSA enhanced the mobilization of splenic HSPCs following GM-CSF administration and increased the number of CD11b+Gr1+ cells in BM and spleen. Increased numbers of Gr1+ cells, which suppressed T cell proliferation, were recovered from spleens of TSA-treated mice. Overall, HDACi enhance MDSC expansion in vitro and in vivo, suggesting that acetylation regulates myeloid cell differentiation. These findings establish a clinically applicable approach to augment this rare and potent suppressive immune cell population and support a novel mechanism underlying the anti-inflammatory action of HDACi.
Soluble β-glucan fromGrifola frondosainduces proliferation and Dectin-1/Syk signaling in resident macrophages via the GM-CSF autocrine pathway
Authors: Masuda Yuki , Togo Takuya , Mizuno Shigeto , Konishi Morichika , Nanba Hiroaki 
Published: October 2011

ABSTRACTMD-Fraction, a highly purified, soluble β-(1,3) (1,6)-glucan obtained from Grifola frondosa (an oriental edible mushroom), has been reported to inhibit tumor growth by modulating host immunity. β-Glucan, a major component of the fungal cell wall, is generally recognized by PRRs expressed on macrophages and DCs, such as Dectin-1, and the ability of β-glucans to modulate host immunity is influenced by their structure and purity. Most cellular studies have used particulate β-glucans, such as yeast zymosan (crude β-glucan) and curdlan (purified β-glucan). However, little is known about the cellular mechanism of soluble β-glucans, including MD-Fraction, despite significant therapeutic implications. In this study, we investigated the cellular mechanism of MD-Fraction in murine resident macrophages and compared it with two well-known β-glucan particles. MD-Fraction induced GM-CSF production rapidly through Dectin-1-independent ERK and p38 MAPK activation. Subsequently, MD-Fraction-induced GM-CSF enhanced proliferation and Dectin-1 expression, which permitted Dectin-1-mediated TNF-α induction through the Syk pathway. Curdlan induced not only the proliferation and activation of Dectin-1/Syk signaling in a manner similar to MD-Fraction but also the uncontrolled, proinflammatory cytokine response. Contrastingly, zymosan reduced proliferation and Dectin-1 expression significantly, indicating that the mechanism of macrophage activation by MD-Fraction differs from that of zymosan. This is the first study to demonstrate that purified β-glucans, such as MD-Fraction and curdlan, induce GM-CSF production directly, resulting in Dectin-1/Syk activation in resident macrophages. In conclusion, we demonstrated that MD-Fraction induces cell proliferation and cytokine production without excessive inflammation in resident macrophages, supporting its immunotherapeutic potential.
The emerging role of leukocyte immunoglobulin-like receptors (LILRs) in HIV-1 infection
Authors: Lichterfeld Mathias , Yu Xu G 
Published: October 2011

ABSTRACT
LILRs represent a group of immunomodulatory molecules that regulate the functional properties of professional APCs and influence immune activation in a variety of disease contexts. Many members of the LILR family recognize peptide/MHC class I complexes as their physiological ligands, and increasing evidence suggests that such interactions are prominently influenced by polymorphisms in HLA class I alleles or sequence variations in the presented antigenic peptides. Emerging data show that LILRs are involved in multiple, different aspects of HIV-1 disease pathogenesis and may critically influence spontaneous HIV-1 disease progression. Here, we review recent progress in understanding the role of LILR during HIV-1 infection by focusing on the dynamic interplay between LILR and HLA class I molecules in determining HIV-1 disease progression, the effects of HIV-1 mutational escape on LILR-mediated immune recognition, the contribution of LILR to HIV-1-associated immune dysfunction, and the unique expression patterns of LILR on circulating myeloid DCs from elite controllers, a small subset of HIV-1-infected patients with natural control of HIV-1 replication. Obtaining a more complete understanding of LILR-mediated immune regulation during HIV-1 infection may ultimately allow for improved strategies to treat or prevent HIV-1-associated disease manifestations.
Effects of ocean-acidification-induced morphological changes on larval swimming and feeding
Authors: Chan Kit Yu Karen , Grünbaum Daniel , O'Donnell Michael J. 
Published: October 2011

SUMMARYReduction in global ocean pH due to the uptake of increased atmospheric CO2 is expected to negatively affect calcifying organisms, including the planktonic larval stages of many marine invertebrates. Planktonic larvae play crucial roles in the benthic–pelagic life cycle of marine organisms by connecting and sustaining existing populations and colonizing new habitats. Calcified larvae are typically denser than seawater and rely on swimming to navigate vertically structured water columns. Larval sand dollars Dendraster excentricus have calcified skeletal rods supporting their bodies, and propel themselves with ciliated bands looped around projections called arms. Ciliated bands are also used in food capture, and filtration rate is correlated with band length. As a result, swimming and feeding performance are highly sensitive to morphological changes. When reared at an elevated PCO2 level (1000 ppm), larval sand dollars developed significantly narrower bodies at fourand six-arm stages. Morphological changes also varied between four observed maternal lineages, suggesting within-population variation in sensitivity to changes in PCO2 level. Despite these morphological changes, PCO2 concentration alone had no significant effect on swimming speeds. However, acidified larvae had significantly smaller larval stomachs and bodies, suggesting reduced feeding performance. Adjustments to larval morphologies in response to ocean acidification may prioritize swimming over feeding, implying that negative consequences of ocean acidification are carried over to later developmental stages.
Static inflation and deflation pressure–volume curves from excised lungs of marine mammals
Authors: Fahlman Andreas , Loring Stephen H. , Ferrigno Massimo , Moore Colby , Early Greg , Niemeyer Misty , Lentell Betty , Wenzel Frederic , Joy Ruth , Moore Michael J. 
Published: October 2011

SUMMARY
Excised lungs from eight marine mammal species [harp seal (Pagophilus groenlandicus), harbor seal (Phoca vitulina), gray seal (Halichoerus grypush), Atlantic white-sided dolphin (Lagenorhynchus acutus), common dolphin (Delphinus delphis), Risso's dolphin (Grampus griseus), long-finned pilot whale (Globicephala melas) and harbor porpoise (Phocoena phocoena)] were used to determine the minimum air volume of the relaxed lung (MAV, N=15), the elastic properties (pressure–volume curves, N=24) of the respiratory system and the total lung capacity (TLC). Our data indicate that mass-specific TLC (sTLC, l kg–1) does not differ between species or groups (odontocete vs phocid) and agree with that estimated (TLCest) from body mass (Mb) by applying the equation: TLCest=0.135 Mb0.92. Measured MAV was on average 7% of TLC, with a range from 0 to 16%. The pressure–volume curves were similar among species on inflation but diverged during deflation in phocids in comparison with odontocetes. These differences provide a structural basis for observed species differences in the depth at which lungs collapse and gas exchange ceases.
Non-invasive study ofOctopus vulgarisarm morphology using ultrasound
Authors: Margheri Laura , Ponte Giovanna , Mazzolai Barbara , Laschi Cecilia , Fiorito Graziano 
Published: October 2011

SUMMARYOctopus arms are extremely dexterous structures. The special arrangements of the muscle fibers and nerve cord allow a rich variety of complex and fine movements under neural control. Historically, the arm structure has been investigated using traditional comparative morphological ex vivo analysis. Here, we employed ultrasound imaging, for the first time, to explore in vivo the arms of the cephalopod mollusc Octopus vulgaris. Sonographic examination (linear transducer, 18 MHz) was carried out in anesthetized animals along the three anatomical planes: transverse, sagittal and horizontal. Images of the arm were comparable to the corresponding histological sections. We were able, in a non-invasive way, to measure the dimensions of the arm and its internal structures such as muscle bundles and neural components. In addition, we evaluated echo intensity signals as an expression of the difference in the muscular organization of the tissues examined (i.e. transverse versus longitudinal muscles), finding different reflectivity based on different arrangements of fibers and their intimate relationship with other tissues. In contrast to classical preparative procedures, ultrasound imaging can provide rapid, destruction-free access to morphological data from numerous specimens, thus extending the range of techniques available for comparative studies of invertebrate morphology.
Carbon isotopic fractionation in eider adipose tissue varies with fatty acid structure: implications for trophic studies
Authors: Budge Suzanne M. , Wang Shiway W. , Hollmén Tuula E. , Wooller Matthew J. 
Published: October 2011

SUMMARYCarbon isotopic fractionation was investigated in fatty acids (FA) of adipose tissue and blood serum of threatened Steller's eiders (Polysticta stelleri) and spectacled eiders (Somateria fischeri) relative to the FA in their diets. Captive eiders were fed a known diet for 180 days with serum sampled at 60, 120 and 180 days immediately after a 12 fast; adipose was collected at 180 days. Essential FA (EFA) in the adipose showed varying degrees of isotope fractionation (0–4‰), depending on FA structure. The δ13C values of long-chain FA 20:5n-3 and 22:6n-3 did not differ from those in the diet, while those of 18:2n-6 and 18:3n-3 were ∼2‰ greater than in the diet. The δ13C values of free FA (FFA) in serum were not consistent within individuals or sampling dates; fractionation varied randomly, suggesting that FFA were arising from diet, rather than mobilization from adipose tissue. Discrimination factors were used in combination with a mixing model incorporating FA and lipid concentrations to estimate the diet of eiders fed a binary mixture with contrasting isotopic signatures. Diet estimates varied with FA but mean values closely approximated the actual proportions consumed. By tracking EFA, this study avoided the complications in interpretation arising from isotopic routing of carbon in bulk isotope analyses and serves as a basis for the development of compound-specific isotopic methods to trace dietary input in wild eiders. However, our understanding of the processes contributing to the variation in isotopic signatures of FA in nature is currently limited, and we recommend that future research directions focus on elucidating these mechanisms.
Penguin head movement detected using small accelerometers: a proxy of prey encounter rate
Authors: Kokubun Nobuo , Kim Jeong-Hoon , Shin Hyoung-Chul , Naito Yasuhiko , Takahashi Akinori 
Published: October 2011

SUMMARY
Determining temporal and spatial variation in feeding rates is essential for understanding the relationship between habitat features and the foraging behavior of top predators. In this study we examined the utility of head movement as a proxy of prey encounter rates in medium-sized Antarctic penguins, under the presumption that the birds should move their heads actively when they encounter and peck prey. A field study of free-ranging chinstrap and gentoo penguins was conducted at King George Island, Antarctica. Head movement was recorded using small accelerometers attached to the head, with simultaneous monitoring for prey encounter or body angle. The main prey was Antarctic krill (&gt;99% in wet mass) for both species. Penguin head movement coincided with a slow change in body angle during dives. Active head movements were extracted using a high-pass filter (5 Hz acceleration signals) and the remaining acceleration peaks (higher than a threshold acceleration of 1.0 g) were counted. The timing of head movements coincided well with images of prey taken from the back-mounted cameras: head movement was recorded within ±2.5 s of a prey image on 89.1±16.1% (N=7 trips) of images. The number of head movements varied largely among dive bouts, suggesting large temporal variations in prey encounter rates. Our results show that head movement is an effective proxy of prey encounter, and we suggest that the method will be widely applicable for a variety of predators.