bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sepsis-Induced Apoptosis Leads to Active Suppression of Delayed-Type Hypersensitivity by CD8+ Regulatory T Cells through a TRAIL-Dependent Mechanism
Authors: Unsinger Jacqueline , Kazama Hirotaka , McDonough Jacqueline S. , Griffith Thomas S. , Hotchkiss Richard S. , Ferguson Thomas A. 
Published: May 2010

Abstract
Patients who survive severe sepsis often display severely compromised immune function. One hallmark of such immune suppression in septic patients is an impaired delayed-type hypersensitivity (DTH) response, manifested by a loss of skin testing to recall Ags. Because sepsis induces significant apoptosis in lymphoid and myeloid cells, and apoptotic cells are themselves tolerogenic, we tested the hypothesis that suppression of DTH is mediated by tolerogenic properties of the apoptotic cells generated during sepsis. Mice subjected to cecal ligation and puncture demonstrated a loss of DTH for the 7 d following cecal ligation and puncture; however, the immune response returned to normal by day 10. Blocking sepsis-induced apoptosis via Bcl-2 overexpression or Bim deficiency prevented the loss of DTH. Importantly, injection of apoptotic cells into Bim−/− mice prevented an effective DTH response, thereby suggesting a causal link between apoptotic cells and immune suppression. Surprisingly, when TRAIL null mice were examined, we found that these animals had significant apoptosis but retained their DTH responses. Further studies revealed that apoptotic cells generated during sepsis induced a CD8+ regulatory T cell that suppressed DTH by TRAIL production. These results establish a link between apoptotic cells and immune suppression during sepsis and suggest TRAIL may be a viable therapeutic target for boosting the adaptive immune response following sepsis.
Stabilization of an E3 Ligase–E2–Ubiquitin Complex Increases Cell Surface MHC Class I Expression
Authors: Duncan Lidia M. , Nathan James A. , Lehner Paul J. 
Published: May 2010

Abstract
The Kaposi’s sarcoma-associated herpesvirus-encoded ubiquitin E3 ligase K3 ubiquitinates cell-surface MHC class I molecules (MHC I), causing the internalization and degradation of MHC I via the endolysosomal pathway. K3 recruits the cellular E2 ubiquitin-conjugating enzyme Ubc13 to generate lysine-63–linked polyubiquitin chains on MHC I, leading to the clathrin-mediated endocytosis and lysosomal degradation of MHC I. In this study, we identify a ubiquitin isoleucine-44-alanine mutant (I44A) that inhibits K3-mediated downregulation of MHC I by preventing MHC I polyubiqitination. This E3-specific inhibition by I44A prevents dissociation of the MHC I–K3–Ubc13–ubiquitin complex, allows the in vivo visualization of a transient substrate–E3–E2–ubiquitin complex interaction, and highlights a potential substrate hierarchy between the different MHC I alleles downregulated by K3. The I44A mutant also increases cell-surface MHC I expression in control cells in the absence of K3, predicting the presence of an endogenous E3 ubiquitin ligase required for cell-surface MHC I regulation.
Identification of Complin, a Novel Complement Inhibitor that Targets Complement Proteins Factor B and C2
Authors: Kadam Archana P. , Sahu Arvind 
Published: May 2010

Abstract
Complement factor B (fB) is a key constituent of the alternative pathway (AP). Its central role in causing inflammation and tissue injury through activation of the AP urges the need for its therapeutic targeting. In the current study, we have screened phage-displayed random peptide libraries against fB and identified a novel cyclic hendecapeptide that inhibits activation of fB and the AP. Structure-activity studies revealed that: 1) the cysteine-constrained structure of the peptide is essential for its activity; 2) Ile5, Arg6, Leu7, and Tyr8 contribute significantly to its inhibitory activity; and 3) retro-inverso modification of the peptide results in loss of its activity. Binding studies performed using surface plasmon resonance suggested that the peptide has two binding sites on fB, which are located on the Ba and Bb fragments. Studies on the mechanism of inhibition revealed that the peptide does not block the interaction of fB with the activated form of C3, thereby suggesting that the peptide inhibits fB activation primarily by inhibiting its cleavage by factor D. The peptide showed a weak effect on preformed C3 and C5 convertases. Like inhibition of fB cleavage, the peptide also inhibited C2 cleavage by activated C1s and activation of the classical as well as lectin pathways. Based on its inhibitory activities, we named the peptide Complin.
Household demand analysis of organic and conventional fluid milk in the United States based on the 2004 Nielsen Homescan panel
Authors: Alviola Pedro A. , Capps Oral 
Published: May 2010

AbstractUsing the 2004 AC Nielsen panel consisting of over 38,000 households, the authors ascertain the influence of selected demographic variables associated with the purchase of organic fluid milk through the estimation of a probit model. From the use of the Heckman two‐step procedure, they also calculate own‐price, cross‐price, and income elasticities by estimating demand relationships for both organic and conventional milk. They find that demographic factors play a crucial role in the household choice of purchasing organic milk. Furthermore, households are more sensitive to own‐price changes in the case of organic milk versus conventional milk. Evidence from estimated cross‐price elasticities indicates that organic and conventional milk are substitutes. However, quantities purchased of organic milk are more sensitive to changes in prices of conventional milk than vice versa. Consequently, an asymmetric pattern exists with regard to the substitution patterns of the respective milk types. Moreover, evidence indicates that organic milk is responsive to income changes, but conventional milk is not responsive to income changes. Finally, a 1% increase in the price of organic milk reduces total milk sales by 0.20%, but a 1% increase in the price of conventional milk raises total milk sales by 0.31%. [EconLit citations: C25, D12]. © 2010 Wiley Periodicals, Inc.
Does lamb promotion work?
Authors: Williams Gary W. , Capps Oral , Dang Trang 
Published: May 2010

AbstractThree key questions regarding lamb promotion are addressed: (a) Have industry efforts to promote lamb shifted out the total demand for lamb? (b) Have any returns to producers achieved been greater than the cost of the promotion? (c) What has been the effect of lamb promotion on the lamb import share? The first question is addressed through an econometric analysis of the U.S. retail demand for lamb, which takes into account the effects of lamb advertising and promotion expenditures. The results then are used to calculate a benefit‐cost ratio for lamb promotion in answer to the second question. An econometric analysis of the import share of U.S. lamb consumption provides the basis for addressing the third question. Lamb promotion is found to have increased the demand for lamb, and particularly American lamb, generating in the process a highly positive return to producers relative to the small cost of the program. [EconLit Classification: D11, D12, Q13, Q17, Q18]. © 2010 Wiley Periodicals, Inc.
Disease Stage Characterization of Hepatorenal Fibrocystic Pathology in the PCK Rat Model of ARPKD
Authors: Mason Stephen B. , Liang Yun , Sinders Rachel M. , Miller Caroline A. , Eggleston‐Gulyas Tracy , Crisler‐Roberts Robin , Harris Peter C. , Gattone Vincent H. 
Published: May 2010

AbstractThe rat Pck gene is orthologous to the human PKHD1 gene responsible for autosomal recessive polycystic kidney disease (ARPKD). Both renal and hepatic fibrocystic pathology occur in ARPKD. Affected humans have a variable rate of progression, from morbidly affected infants to those surviving into adulthood. This study evaluated the PCK rat, a model of slowly progressive ARPKD. This model originated in Japan and was rederived to be offered commercially by Charles River Laboratories (Wilmington, MA). Previous studies have described the basic aspects of PCK pathology from privately held colonies. This study provides a comprehensive characterization of rats from those commercially available. Rats were bred, maintained on a 12:12 hr light/dark cycle, fed (7002 Teklad), and water provided ad libitum. Male and female rats were evaluated from 4 through 35 weeks of age with histology and serum chemistry. As the hepatorenal fibrocystic disease progressed beyond 18 weeks, the renal pathology (kidney weight, total cyst volume) and renal dysfunction (BUN and serum creatinine) tended to be more severe in males, whereas liver pathology (liver weight as % of body weight and hepatic fibrocystic volume) tended to be more severe in females. Hyperlipidemia was evident in both genders after 18 weeks. Bile secretion was increased in PCK rats compared with age‐matched Sprague Dawley rats. The PCK is an increasingly used orthologous rodent model of human ARPKD. This characterization study of hepatorenal fibrocystic pathology in PCK rats should help researchers select stages of pathology to study and/or monitor disease progression during their longitudinal studies. Anat Rec 293:1279–1288, 2010. © 2010 Wiley‐Liss, Inc.
Effects of Monochromatic Light on Developmental Changes in Satellite Cell Population of Pectoral Muscle in Broilers During Early Posthatch Period
Authors: Liu Wenjie , Wang Zixu , Chen Yaoxing 
Published: May 2010

AbstractTo investigate the effects of various monochromatic lights on early posthatch changes in satellite cell mitotic activity of pectoral muscle, a total of 416 newly hatched broilers were exposed to blue light (BL), green light (GL), red light (RL), and white light (WL) by light emitting diode system for 3 weeks, respectively. Both, in culture and in vivo studies showed that after hatching, the relative number of satellite cells altered in correlation. The enhancement of satellite cell mitotic activity peaked at post‐hatching day (P) 3 and then declined with age concomitantly with the rise in satellite cell differentiation and reduction of satellite cell proliferation. These alterations became more obvious in GL than in RL. The data suggested that early posthatch changes in satellite cell population of broilers occurred through the two different processes, i.e., cellular generation (before P3) and cellular degeneration (after P3). GL promoted significantly the broiler satellite cells to proliferate before P3 and to differentiate after P3. In addition, the circulating insulin‐like growth factor‐I (IGF‐I) levels were higher in GL and BL groups versus WL and RL groups at P3 and P5 indicating that IGF‐I plays a central role for GL illumination promoting broiler satellite cell myogenic processes during early posthatch stages. Anat Rec 293:1315–1324, 2010. © 2010 Wiley‐Liss, Inc.
Temporal and Spatial Distribution of the Cannabinoid Receptors (CB1, CB2) and Fatty Acid Amide Hydroxylase in the Rat Ovary
Authors: Bagavandoss P. , Grimshaw S. 
Published: May 2010

AbstractAlthough the effects of Δ9‐tetrahydrocannabinol (THC) on ovarian physiology have been known for many decades, its mechanism of action in the rat ovary remains poorly understood. The effects of THC and endocannabinoids on many cell types appear to be mediated through the G‐protein‐coupled CB1and CB2receptors. Evidence also suggests that the concentration of the endocannabinoid anandamide is regulated by cellular fatty acid amide hydrolase (FAAH). Therefore, we examined the rat ovary for the presence of CB1and CB2receptors and FAAH. The CB1receptor was present in the ovarian surface epithelium (OSE), the granulosa cells of antral follicles, and the luteal cells of functional corpus luteum (CL). The granulosa cells of small preantral follicles, however, did not express the CB1receptor. Western analysis also demonstrated the presence of a CB1receptor. In both preantral and antral follicles, the CB2receptor was detected only in the oocytes. In the functional CL, the CB2receptor was detected in the luteal cells. FAAH was codistributed with CB2receptor in both oocytes and luteal cells. FAAH was also present in the OSE, subepithelial cords of the tunica albuginea (TA) below the OSE, and in cells adjacent to developing preantral follicles. Western analysis also demonstrated the presence of FAAH in oocytes of both preantral and antral follicles. Our observations provide potential explanation for the effects of THC on steroidogenesis in the rat ovary observed by earlier investigators and a role for FAAH in the regulation of ovarian anandamide. Anat Rec 293:1425–1432, 2010. © 2010 Wiley‐Liss, Inc.
The Neonatal Ilium—Metaphyseal Drivers and Vascular Passengers
Authors: Cunningham Craig A. , Black Sue M. 
Published: May 2010

AbstractAt birth the newborn is equipped with a developing locomotor apparatus, which will ultimately become involved in load transfer from the period when the child adopts a sitting posture through to the attainment of a bipedal gait. This load transfer has been considered to influence trabecular bone structural organization by setting up forces, which remodel the internal architecture into a functionally optimized form. However, during the neonatal developmental period the locomotor apparatus is nonweight bearing and instead only supports reflexive movements. Surprisingly, a structural organization has been identified within the internal trabecular architecture and external cortical morphology of the neonatal ilium, which appears to mimic the structural composition of the more mature bone. This study aims to build upon previous qualitative and quantitative investigation of this apparently precocious patterning by further examining structural data obtained from selected volumes of interest within the ilium. Analysis has revealed statistically significant differences in regional trabecular and cortical bone characteristics, which have formed the basis of a possible growth model for the ilium. Volumetric comparison has demonstrated the presence of three progressive “growth regions” and three “restricted growth regions,” which appear to relate to metaphyseal and nonmetaphyseal borders of the ilium. Therefore, the structural data and statistical analysis presented in this study challenge the current concept of implied centrifugal ossification within the human ilium and present evidence of an alternative pattern of ossification that is largely dictated and controlled by vascular distribution and growth plate position. Anat Rec 293:1297–1309, 2010. © 2010 Wiley‐Liss, Inc.
Stereological Investigation of Age‐Related Changes of the Capillaries in White Matter
Authors: Shao Wei‐Hua , Li Chen , Chen Lin , Qiu Xuan , Zhang Wei , Huang Chun‐Xia , Xia Lei , Kong Ji‐Ming , Tang Yong 
Published: May 2010

AbstractWe, for the first time, investigated the age‐related changes of the capillaries in white matter using immunohistochemistry and stereological techniques. Ten young female (7 months) and 10 aged female (27 months) rats were used. The total length, total volume, and total surface area of the capillaries in white matter of aged rats were all significantly lower than those of young rats. The age‐related changes of the capillaries in white matter may have important implications for age‐related white matter atrophy and age‐related cognitive impairments. Anat Rec 293:1400–1407, 2010. © 2010 Wiley‐Liss, Inc.
Combinatorial Synthesis of Deoxyhexasaccharides Related to the Landomycin A Sugar Moiety, Based on an Orthogonal Deprotection Strategy
Authors: Tanaka Hiroshi , Yamaguchi Sho , Yoshizawa Atsushi , Takagi Motoki , Shin‐ya Kazuo , Takahashi Takashi 
Published: May 2010

AbstractIn this report, we describe the stereoselective synthesis of a combinatorial library comprised of 16 deoxyhexasaccharides that are related to a landomycin A sugar moiety, based on an orthogonal deprotection strategy. The use of an olivosyl donor containing a benzyl ether at the C3 position and benzoyl ester at the C4 position, and the olivosyl donor, a naphthylmethyl ether, and a p‐nitrobenzylethyl or benzyl sulfonyl ester enabled the synthesis of a set of four diolivosyl units containing a hydroxyl group at the C3 or C4 position by a simple glycosylation and deprotection procedure. Using a phenylthio 2,3,6‐trideoxyglycoside, α‐selective glycosidation proceeded without anomerization of the 2,6‐dideoxy‐β‐glycosides. In addition, alkylhydroquinone and levulinoyl groups were found to be an effective set of orthogonal protecting groups for the anomeric position and a hydroxyl group. The coupling of all combinations of trisaccharide units in a β‐selective manner was accomplished by activation of the glycosyl imidate with I2 and Et3SiH. No cleavage of the acid‐labile 2,3,6‐trideoxyglycoside was observed under the conditions used for the reactions. Finally, all of the protected hexasaccharides were deprotected by hydrolysis of the esters, microwave (MW) assisted cleavage of the 2‐trimethylsilylethoxymethoxy (SEM) ether, and a Birch reduction.
Improved controllability test for dependent siphons in S3PR based on elementary siphons
Authors: Chao Daniel Y. 
Published: May 2010

AbstractWhen siphons in a flexible manufacturing system (FMS) modeled by an ordinary Petri net (OPN) become unmarked, the net gets deadlocked. To prevent deadlocks, some control places and related arcs are added to strict minimal siphons (SMS) so that no siphon can be emptied. For large systems, it is infeasible to add a monitor to every SMS since the number of SMS or control elements grows exponentially with respect to the size of a Petri net. To tackle this problem, Li and Zhou propose to add control nodes and arcs for only elementary siphons. The rest of siphons, called dependent ones, may be controlled by adjusting control depth variables of elementary siphons associated with a dependent siphon after the failure of two tests. First, they test a Marking Linear Inequality (MLI); if it fails, then they perform a Linear Integer Programming (LIP) test which is an NP‐hard problem. This implies that the MLI test is only sufficient, but not necessary. We propose a sufficient and necessary test for adjusting control depth variables in an S3PR to avoid the sufficient‐only time‐consuming linear integer programming (LIP) test (NP‐complete problem) required previously for some cases. We theoretically prove the following: i) no need for LIP test for Type II siphons; and ii) Type I strongly n‐dependent (n>2) siphons being always marked. As a result, the total time complexity to check controllability of all strongly dependent siphons is no longer exponential but reduced to linear if all siphons are of Type I. The total time complexity is O(|ΠE||ΠD|) (order of the product of total number of elementary siphons and total number of dependent siphons) if all siphons are of Type II. A well‐known S3PR example has been illustrated to show the advantages. Copyright © 2010 John Wiley and Sons Asia Pte Ltd and Chinese Automatic Control Society
Impact of regulatory focus on ambiguity aversion
Authors: Liu Hsin‐Hsien 
Published: May 2010

AbstractAlthough prior research has shown that some people prefer a risky to an ambiguous option, this study further proposes that people's regulatory focus (promotion vs. prevention) might influence their ambiguity aversion. Three experiments have tested whether people with promotion focus showed less ambiguity aversion than those with prevention focus: The first experiment revealed that, compared with chronically promotion‐focused individuals, prevention‐focused subjects preferred a risky to an ambiguous option. In the second experiment, priming of the subjects' goal orientations led to similar results. Experiment 3 demonstrated that participants showed less ambiguity aversion for the expected performance of an investment product representative of promotion (e.g., a stock fund) rather than one representative of prevention (e.g., a bond fund). In other words, people showed less preference for a bond fund when the probability distribution of its expected performance was unknown than when it was known, whereas they showed less preference difference between known and unknown probability distributions for the expected performance of a stock fund. This study has integrated research pertaining to regulatory focus and ambiguity aversion, and the results have confirmed that the impact of regulatory focus on ambiguity aversion is robust across different methods and decision tasks. Copyright © 2010 John Wiley & Sons, Ltd.
Glucocorticoid receptor‐mediated reduction of IgG‐fusion protein aggregation in Chinese hamster ovary cells
Authors: Qian Yueming , Jing Ying , Li Zheng Jian 
Published: May 2010

AbstractFormation of high molecular weight (HMW) species is a common issue encountered during manufacture of protein therapeutics. With advanced purification techniques, efficient removal of protein aggregates is no longer a challenging task, but it is important to minimize protein aggregation level at the culture stage to reduce the downstream burden and improve overall process yield. In this regard, our recent effort on medium optimization has led us to unexpectedly discover that glucocorticoids can significantly reduce the formation of HMW species in IgG‐fusion protein produced by CHO cells. First, the effectiveness of dexamethasone can be seen at nanomolar concentrations, which allows this glucocorticoid analog to be a cost‐efficient chemical for reducing protein aggregation in cell cultures. Second, this reduction is mediated through glucocorticoid receptors (GR) as it is antagonized by GR antagonist RU486. Third, GR activation upregulates expression of glutathione reductase but not protein disulfide‐isomerase, which may help with providing a balanced redox condition in the cells. Last, the beneficial effect of dexamethasone is not limited to one cell line, and it can be repeated in a different cell line, indicating that glucocorticoids are also applicable to other DG44 cell lines for reducing protein aggregation. © 2010 American Institute of Chemical Engineers Biotechnol. Prog., 2010
Incorporation of 2,3‐Diaminopropionic Acid into Linear Cationic Amphipathic Peptides Produces pH‐Sensitive Vectors
Authors: Lan Yun , Langlet‐Bertin Bérangère , Abbate Vincenzo , Vermeer Louic S. , Kong Xiaole , Sullivan Kelly E. , Leborgne Christian , Scherman Daniel , Hider Robert C. , Drake Alex F. , Bansal Sukhvinder S. , Kichler Antoine , Mason A. James 
Published: May 2010

AbstractNonviral vectors that harness the change in pH in endosomes, are increasingly being used to deliver cargoes, including nucleic acids, into mammalian cells. Here we present evidence that the pKa of the β‐NH2 in 2,3‐diaminopropionic acid (Dap) is sufficiently lowered, when Dap is incorporated into peptides, that its protonation state is sensitive to the pH changes that occur during endosomal acidification. The lowered pKa of around 6.3 is stabilized by the increased electron‐withdrawing effect of the peptide bonds, by intermolecular hydrogen bonding and from contributions arising from the peptide conformation. These include mixed polar/apolar environments, Coulombic interactions and intermolecular hydrogen bonding. Changes in the charged state are therefore expected between pH 5 and 7, and large‐scale conformational changes are observed in Dap‐rich peptides, in contrast to analogues containing lysine or ornithine, when the pH is altered through this range. These physical properties confer a robust gene‐delivery capability on designed cationic amphipathic peptides that incorporate Dap.