bluuebunny/crossref_metadata_2025 huggingface dataset:
Natural selection on inflorescence color polymorphisms in wildProteapopulations: The role of pollinators, seed predators, and intertrait correlations
Authors: Carlson Jane E. , Holsinger Kent E.
Published: May 2010

•Premise of the study:The processes maintaining flower color polymorphisms have long been of evolutionary interest. Mechanistic explanations include selection through pollinators, antagonists, local environments, drift, and pleiotropic effects. We examined the maintenance of inflorescence color polymorphisms in the genusProtea(Proteaceae) of South Africa, in which ∼40% of species contain different color morphs.

•Methods:We studied 10 populations of four bird‐pollinatedProteaspecies and compared adult performance, floral and leaf morphology, vegetative pigmentation, germination, and seedling survival between co‐occurring pink and white morphs. We also tested for differences in pollination success and pre‐dispersal seed predation.

•Key results:White morphs produced seeds 10% heavier and 3.5 times more likely to germinate, which all else being equal, should fuel positive selection on white. In one studied population per species, however, white morphs were more susceptible to seed predation by endophagous larvae. Pollinators had no morph‐specific effects on female fecundity, as measured by amount or probability of seed set. Differences in stem color indicated that white morphs produced smaller quantities of pigment and associated compounds throughout, possibly explaining their higher seed palatability.

•Conclusions:Our findings suggest a mechanism for some white protea polymorphisms: deleterious pleiotropic effects on pink morphs are occasionally offset by reduced losses to seed‐eating larvae. Because trends were repeated across species, we suggest that similar processes may also occur in other proteas, placing a new emphasis on seed predators for influencing some of South Africa's amazing floral diversity.
Mixed mating in a recently derived self‐compatible population of Leavenworthia alabamica (Brassicaceae)
Authors: Busch Jeremiah W. , Herlihy Christopher R. , Gunn Lena , Werner William J.
Published: May 2010

• Premise of the study: A mixture of outcrossing and selfing is often observed in plant populations. Although mixed mating is ubiquitous, it has several potential evolutionary explanations. Mixed mating may be actively maintained by selection, passively determined by the pollination environment, or a transitional stage during the evolution of self‐fertilization.

• Methods: We studied patterns of self‐compatibility and selfing rates in a population of Leavenworthia alabamica that recently lost self‐incompatibility. We also experimentally tested whether natural selection against selfing at the pre‐ or postzygotic stage is sufficient to explain mixed mating in this population.

• Key results: Visualizing pollen tube growth following self‐pollination, we found that nearly all plants were fully self‐compatible. Progeny array analysis revealed that the average selfing rate of the population was s = 0.523. The inbreeding coefficient in the parents (F = 0.539) exceeded the amount expected if the selfing rate (s) were constant [Feq = s/(2 − s)], indicating either population subdivision or higher selfing rates in the past. Inference of family‐level selfing rates revealed substantial variation. Experiments found that self and outcross pollen fertilized nearly equal numbers of ovules in competition. Comparison of seed production following self‐ or cross‐pollination failed to implicate early acting inbreeding depression as a factor maintaining mixed mating.

• Conclusions: The results of our experiments suggest that mixed mating is not maintained by selection against self‐pollen or zygotes in this population. Mixed mating is most likely a byproduct of the pollination process but may also be a transitional stage during the evolution of higher selfing rates.
El capitán Miguel Caldera y la frontera chichimeca: entre el mestizo historiográfico y el soldado del rey
Authors: Ruiz Guadalajara Juan Carlos
Published: May 2010

Este artículo intenta un acercamiento crítico a la imagen que la historiografía contemporánea ha construido en torno a la figura del capitán Miguel Caldera. Muestra, en contraste, elementos que nos aproximan a su identidad hispánica, a su papel como miliciano al servicio de Felipe II y a su función como vehículo de la dominación y desaparición de los nómadas de la frontera chichimeca. También pretende aportar elementos de discusión sobre el proceso cultural fronterizo en el ámbito de la expansión de la monarquía hispánica en el siglo XVI.
De cómo Don Dieguillo, indio cuechale, vivió dos vidas, la propia y la que le colgaron
Authors: Valdés Carlos Manuel
Published: May 2010

Don Dieguillo, indio cuechale que vivió a finales del siglo XVII y principios del XVIII, pasó de colaborador de los españoles a ser acusado de destruir una misión. Finalmente, la captura de otros indios con enseres pertenecientes al establecimiento evangélico demostró la falsedad de los cargos, pero el suceso sirve para analizar las relaciones entre las autoridades civiles y religiosas, locales y lejanas, y los indígenas norteños.
Valerio Cortés del Rey, fundador del único mayorazgo de la Nueva Vizcaya en el siglo XVII
Authors: Cramaussel Chantal
Published: May 2010

Valerio Cortés del Rey pertenecía a la pequeña nobleza de la ciudad de Zaragoza. Arribó al Nuevo Mundo en 1621 y ascendió con notable celeridad todos los peldaños de la sociedad. Mientras trabajaba de barretero, guardaminas, ensayador, prestamista, etcétera, adquirió numerosos bienes y propiedades situadas en la frontera norte de la provincia de Santa Bárbara. En la cúspide del éxito, logró un mayorazgo que estuvo en manos de sus descendientes hasta el siglo XIX. La biografía de Valerio Cortés del Rey es una muestra de la gran movilidad social al alcance de los peninsulares que se aventuraban a hacer fortuna en la gobernación de la Nueva Vizcaya.
Roque Zubiate. Las andanzas de un ladrón de ganado en el Septentrión Novohispano (1750-1836)
Authors: Ortelli Sara
Published: May 2010

La biografía de Roque Zubiate es una ventana que permite observar el modo de vida de pequeños rancheros y trabajadores del campo; hombres que, además de la dedicación a las tareas rurales, realizaron actividades consideradas ilícitas por las autoridades coloniales, relacionadas con el abigeato, en connivencia con algunos poderosos locales, de quienes eran, además, hombres de confianza. Esta mirada, que enfoca la trayectoria de un hombre que vivió entre la colonia y los primeros años del periodo independiente y analiza el contexto local, cuestiona el paradigma del bandolerismo como explicación a la presencia de este tipo de fenómenos en las sociedades hispanoamericanas.
Velázquez en el Purgatorio: los días y los trabajos de un científico en California
Authors: Bernabéu Albert Salvador
Published: May 2010

Siguiendo los proyectos del visitador malagueño José de Gálvez, el científico criollo Velázquez de León se ausentó de la Universidad de México y pasó dos años en la lejana península de California. El estudio de este episodio poco conocido de su vida nos revela la diversidad y complejidad de las relaciones sociales en uno de los lugares más remotos de la colonia. Velázquez fracasó en sus intentos por mejorar la minería local y en sus medidas como lugarteniente del visitador, pero escribió varias descripciones de gran interés y ayudó a medir el Paso de Venus desde su residencia de Santa Ana. Su afición a las cartas, a las fiestas y a las mujeres servirá para humanizar una figura demasiado encasillada en laboratorios, oratorios y respetables instituciones ilustradas.
The Microtubule Regulator Stathmin Is an Endogenous Protein Agonist for TLR3
Authors: Bsibsi Malika , Bajramovic Jeffrey J. , Vogt Mario H. J. , van Duijvenvoorden Eveline , Baghat Aabed , Persoon-Deen Carla , Tielen Frans , Verbeek Richard , Huitinga Inge , Ryffel Bernhard , Kros Alexander , Gerritsen Wouter H. , Amor Sandra , van Noort Johannes M.
Published: May 2010

TLR3 recognizes dsRNAs and is considered of key importance to antiviral host-defense responses. TLR3 also triggers neuroprotective responses in astrocytes and controls the growth of axons and neuronal progenitor cells, suggesting additional roles for TLR3-mediated signaling in the CNS. This prompted us to search for alternative, CNS-borne protein agonists for TLR3. A genome-scale functional screening of a transcript library from brain tumors revealed that the microtubule regulator stathmin is an activator of TLR3-dependent signaling in astrocytes, inducing the same set of neuroprotective factors as the known TLR3 agonist polyinosinic:polycytidylic acid. This activity of stathmin crucially depends on a long, negatively charged α helix in the protein. Colocalization of stathmin with TLR3 on astrocytes, microglia, and neurons in multiple sclerosis-affected human brain indicates that as an endogenous TLR3 agonist, stathmin may fulfill previously unsuspected regulatory roles during inflammation and repair in the adult CNS.
Timing of CD8+ T Cell Responses in Relation to Commencement of Capillary Leakage in Children with Dengue
Authors: Dung Nguyen Thi Phuong , Duyen Huynh Thi Le , Thuy Nguyen Thi Van , Ngoc Tran Van , Chau Nguyen Van Vinh , Hien Tran Tinh , Rowland-Jones Sarah L. , Dong Tao , Farrar Jeremy , Wills Bridget , Simmons Cameron P.
Published: May 2010

Immune activation is a feature of dengue hemorrhagic fever (DHF) and CD8+ T cell responses in particular have been suggested as having a role in the vasculopathy that characterizes this disease. By phenotyping CD8+ T cells (CD38+/HLA-DR+, CD38+/Ki-67+, or HLA-DR+/Ki-67+) in serial blood samples from children with dengue, we found no evidence of increased CD8+ T cell activation prior to the commencement of resolution of viremia or hemoconcentration. Investigations with MHC class I tetramers to detect NS3133–142-specific CD8+ T cells in two independent cohorts of children suggested the commencement of hemoconcentration and thrombocytopenia in DHF patients generally begins before the appearance of measurable frequencies of NS3133–142-specific CD8+ T cells. The temporal mismatch between the appearance of measurable surface activated or NS3133–142-specific CD8+ T cells suggests that these cells are sequestered at sites of infection, have phenotypes not detected by our approach, or that other mechanisms independent of CD8+ T cells are responsible for early triggering of capillary leakage in children with DHF.
Type I IFN Receptor Regulates Neutrophil Functions and Innate Immunity to Leishmania Parasites
Authors: Xin Lijun , Vargas-Inchaustegui Diego A. , Raimer Sharon S. , Kelly Brent C. , Hu Jiping , Zhu Leiyi , Sun Jiaren , Soong Lynn
Published: May 2010

Type I IFNs exert diverse effector and regulatory functions in host immunity to viral and nonviral infections; however, the role of endogenous type I IFNs in leishmaniasis is unclear. We found that type I IFNR-deficient (IFNAR−/−) mice developed attenuated lesions and reduced Ag-specific immune responses following infection with Leishmania amazonensis parasites. The marked reduction in tissue parasites, even at 3 d in IFNAR−/− mice, seemed to be indicative of an enhanced innate immunity. Further mechanistic analyses indicated distinct roles for neutrophils in parasite clearance; IFNAR−/− mice displayed a rapid and sustained infiltration of neutrophils, but a limited recruitment of CD11b+Ly-6C+ inflammatory monocytes, into inflamed tissues; interactions between IFNAR−/−, but not wild-type (WT) or STAT1−/−, neutrophils and macrophages greatly enhanced parasite killing in vitro; and infected IFNAR−/− neutrophils efficiently released granular enzymes and had elevated rates of cell apoptosis. Furthermore, although coinjection of parasites with WT neutrophils or adoptive transfer of WT neutrophils into IFNAR−/− recipients significantly enhanced infection, the coinjection of parasites with IFNAR−/− neutrophils greatly reduced parasite survival in WT recipients. Our findings reveal an important role for type I IFNs in regulating neutrophil/monocyte recruitment, neutrophil turnover, and Leishmania infection and provide new insight into innate immunity to protozoan parasites.
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

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

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

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

Using 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

Three 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

The 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

To 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

Although 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

At 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

We, 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

In 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

When 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

Although 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

Formation 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

Nonviral 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.
The Search for Tricyanomethane (Cyanoform)
Authors: Šišak Dubravka , McCusker Lynne B. , Buckl Andreas , Wuitschik Georg , Wu Yi‐Lin , Schweizer W. Bernd , Dunitz Jack D.
Published: May 2010

Although listed in organic chemistry textbooks as one of the strongest carbon acids, and in spite of more than a hundred years of attempts to prepare the compound, tricyanomethane (cyanoform) has resisted isolation and characterization, either as the carbon‐acid 1 or as the dicyanoketenimine tautomer 2. Only in the vapor phase at very low pressure has the compound been identified from its microwave spectrum. Here we review and partially repeat the preparative work. With the aid of spectroscopic and diffraction methods (including powder diffraction) we have identified some of the products obtained as: hydronium tricyanomethanide (3), (Z)‐3‐amino‐2‐cyano‐3‐iminoacrylimide (4), a co‐crystal of 4 with sulfuric acid (or corresponding iminium salt), and an addition product of 2 with hydrochloric acid (5/6). Quantum‐mechanical calculations at the MP2/6‐311++g(2d,2p) level have been made to assess the relative energies of some of the molecules involved.
Investigating by circular dichroism some amyloidogenic elastin‐derived polypeptides
Authors: Tamburro Antonio Mario , Lorusso Marina , Ibris Neluta , Pepe Antonietta , Bochicchio Brigida
Published: May 2010

Tamburro and coworkers have demonstrated that some elastin‐derived polypeptide sequences are able to give rise, in vitro, to amyloid‐like fibers. The biological relevance of this finding could be explained by the recent detection of some amyloidogenic material found in arteries of old patients affected by atherosclerosis and demonstrated to be elastin derived. In this context, the comprehension of the mechanism responsible for the amyloid‐like fibrillogenesis of elastin‐derived sequences is of crucial importance for the design of drugs that could inhibit the amyloidogenic process. To gain further insights into the elastin amyloidogenic process, we studied the polypeptide sequences encoded by Exon 7 and Exon 32 of the human tropoelastin gene, and we demonstrated that only Exon 32 is able to aggregate in amyloid‐like fibers. Vis–UV Thioflavin T circular dichroism (CD) spectroscopy rapidly and unambiguously detected the amyloidogenic propensity of the polypeptides. To gain additional insights into the aggregation mechanism of elastin‐derived amyloidogenic peptides, we carried out the kinetics of EX32 amyloid‐like aggregates by using ThT dye. CD spectroscopy was also used for investigating the secondary structure of the polypeptides, thus giving useful insights into the conformations involved in amyloid‐like fiber formation. Furthermore, complementary techniques such as fluorescence spectroscopy, spectral shift, and binding Congo red UV assays as well as atomic force microscopy were also used to confirm the amyloidogenic behavior of the studied polypeptides. Chirality, 2010. © 2010 Wiley‐Liss, Inc.
Hodgkin lymphoma involving extranodal and nodal head and neck sites
Authors: Iyengar Puneeth , Mazloom Ali , Shihadeh Ferial , Berjawi Ghina , Dabaja Bouthaina
Published: May 2010

BACKGROUND:

Most Hodgkin lymphoma (HL) patients present with disease in nodal regions. However, in a small subset, disease develops in unique anatomic sites such as the head and neck area. This study aims to identify the characteristics and outcomes of patients who develop HL involving extranodal and nodal head and neck sites.

METHODS:

The authors searched The University of Texas M. D. Anderson Cancer Center's database for HL patients treated between 1967 and 2007 and included those with HL at head and neck sites. They reviewed the records for site of involvement, pathology, treatment, and survival.

RESULTS:

The authors identified 39 patients with extranodal and nodal HL of the head and neck. Five patients with lymphocyte predominant HL were excluded. Specifically, 10 of 34 patients had disease in the tonsils, 9 in the nasopharynx, 8 in the thyroid, 3 in the parotid, 2 in the adenoids, and 1 each in Waldeyer's ring and nasal antrum. Median age at diagnosis was 31.5 years, average age at diagnosis was 38 years, and 22 of 34 were male; 23 had stage I or II disease. Pathologically, 14 of 34 had the nodular sclerosis subtype, whereas 15 had mixed cellularity. Twenty‐nine of 34 had nodal neck disease at presentation. Five of 34 received chemotherapy alone, 5 received radiation alone, and 24 received combination therapy. Twenty‐one of 34 received 39.6 gray of external beam radiation. The most commonly used chemotherapy regimens were ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) and MOPP (mechlorethamine, vincristine, procarbazine, and prednisone). At last follow‐up, 85% were disease‐free.

CONCLUSIONS:

HL of the head and neck is primarily diagnosed as early stage disease of men and of young to middle‐aged individuals. Chemotherapy and primary/adjuvant radiotherapy offer excellent local and systemic control. The extent to which nodal disease is present in the neck does not alter outcomes when combined modality therapy is offered. Despite the unique anatomic location of these lesions, standard HL protocols work effectively to promote disease‐free survival. Cancer 2010. © 2010 American Cancer Society.
Agreement between pediatric brain tumor patients and parent proxy reports regarding the Pediatric Functional Assessment of Cancer Therapy–Childhood Brain Tumor Survivors questionnaire, version 2
Authors: Yoo Hee‐Jung , Ra Young‐Shin , Park Hyeon‐Jin , Lai Jin‐Shei , Cella David , Shin Hee‐Young , Kim Dong‐Seok
Published: May 2010

BACKGROUND:

This study investigated the agreement between self‐reports from pediatric brain tumor patients and proxy reports from their parents regarding the patients' quality of life (QOL), as assessed using a brain tumor‐specific QOL assessment tool, the Pediatric Functional Assessment of Cancer Therapy‐Childhood Brain Tumor Survivors (pedsFACT‐BrS) questionnaire. The authors expected moderate correlation and similar mean scores between patient and parent reports.

METHODS:

The pedsFACT‐BrS for those aged 7 to 18 years was completed by 351 brain tumor patients (166 children and 185 adolescents), and the parent proxy reports were completed by 351 mother proxies and 37 father proxies. Statistical analyses, including the Pearson product‐moment correlation coefficient, intraclass correlation, and comparison of group means, were used to compare the 33 items shared by all 4 versions of the pedsFACT‐BrS.

RESULTS:

The correlation between reports completed by pediatric patients and their parent proxies was significant (P = .59‐.84), whereas that between the reports of adolescent patients and their parent proxies was slightly weaker (P = .47‐.78). The patient and parent proxy reports showed moderate‐to‐good agreement and yielded similar mean scores in both the child and adolescent brain tumor patient groups; the sole exception was a difference in emotional well‐being scores.

CONCLUSIONS:

The results indicate that proper use of the pedsFACT‐BrS for patients and their parent proxies can provide clinicians with valid information about the overall QOL of child and adolescent brain tumor patients, including both their general health and their brain tumor‐specific well‐being. Cancer 2010. © 2010 American Cancer Society.
Correlation between Dynamic Heterogeneity and Local Structure in a Room‐Temperature Ionic Liquid: A Molecular Dynamics Study of [bmim][PF6]
Authors: Sarangi Soumya S. , Zhao Wei , Müller‐Plathe Florian , Balasubramanian Sundaram
Published: May 2010

The complex dynamics of a room‐temperature ionic liquid, 1‐n‐butyl‐3‐methylimidazolium hexafluorophosphate ([bmim][PF6]), is studied using equilibrium classical molecular dynamics simulations in the temperature range of 250–450 K. The activation energies for the self‐diffusion of ions are around 30–34 kJ mol−1, with that of the anion a little higher than that for the cation. The electrical conductivity of the liquid is calculated and good agreement with experiments is obtained. Structural relaxation is studied through the decay of coherent (total density–density correlation) and incoherent (self part of density–density correlation) intermediate scattering functions over a range of temperatures and wave vectors relevant to the system. The relaxation data are used to identify and characterize two processes, α and β. The dependence of the two relaxation times on temperature and wave vector is obtained. The dynamical heterogeneity of the ions determined through the non‐Gaussian parameter indicates the motion of the cation to be more heterogeneous than that of the anion. The faster ones among the cations are coordinated to faster anions, while slower cations are surrounded predominantly by slower anions. Thus, the dynamical heterogeneity in this ionic liquid is shown to have structural signatures.
The A1C and ABCD of glycaemia management in type 2 diabetes: a physician's personalized approach
Authors: Pozzilli Paolo , David Leslie R. , Chan Juliana , De Fronzo Ralph , Monnier Louis , Raz Itamar , Del Prato Stefano
Published: May 2010

Recent intervention trials (Veterans Affairs Diabetes Trial, Action to Control Cardiovascular Risk in Diabetes, Action in Diabetes and Vascular Disease) have underscored problems surrounding the risk‐benefit balance of most therapeutic strategies in type 2 diabetes given, especially the limited cardiovascular advantage of tight glycaemic control when set against the co‐incident risk of severe hypoglycaemia and weight gain. Consequently, therapy should to tailored to the individual. While attractive, such an approach remains highly empiric and to some extent difficult to implement without practical guidance, in particular for the inexperienced physician. To provide a user‐friendly guide for a personalized therapeutic approach to type 2 diabetes, we performed a systematic review of the literature and elaborated a simple rule that was debated at a large independent University Symposium on the occasion of the European Association for the Study of Diabetes held in Vienna 2009. As a result of that process, we now propose an A1C and ABCD of glycaemia management in type 2 diabetes to determine appropriate glycaemic targets based on Age, Body weight, Complications and Disease Duration. ‘A1C and ABCD’ aims to guide clinicians in the use of therapeutic agents more effectively, efficiently and safely. While no regulatory‐approved drug can be excluded, given its proven efficacy, there is a need to better phenotype patients, paying particular attention to ABCD. Based on these parameters, physicians can select the therapeutic strategy with minimum risk and maximum benefit for each individual. Copyright © 2010 John Wiley & Sons, Ltd.
BMP regulation of myogenesis in zebrafish
Authors: Patterson Sara E. , Bird Nathan C. , Devoto Stephen H.
Published: May 2010

Twenty‐four hour zebrafish embryo labeled for dermomyotome (green, pax7) and muscle fibers (red, MEF2 and blue, Myosin Heavy Chain). Ectopic BMP signaling causes a delay in myogenesis, leading to an increase in the dermomyotome and a decrease in muscle fibers. From Patterson et al., Developmental Dynamics 239:806–817, 2010.
The interferon‐inducible gene IFI16 secretome of endothelial cells drives the early steps of the inflammatory response
Authors: Baggetta Rossella , De Andrea Marco , Gariano Grazia Rosaria , Mondini Michele , Rittà Massimo , Caposio Patrizia , Cappello Paola , Giovarelli Mirella , Gariglio Marisa , Landolfo Santo
Published: May 2010

The IFN‐inducible human IFI16 gene is highly expressed in endothelial cells as well as epithelial and hematopoietic tissues. Previous gene array analysis of human umbilical vein endothelial cells overexpressing IFI16 has revealed an increased expression of genes involved in inflammation and apoptosis. In this study, protein array analysis of the IFI16 secretome showed an increased production of chemokines, cytokines and adhesion molecules responsible for leukocyte chemotaxis. Functional analysis of the promoter for CCL20, the chemokine responsible for leukocyte recruitment in the early steps of inflammation, by site‐specific mutation demonstrated that NF‐κB is the main mediator of CCL20 induction at the transcriptional level. Finally, both Langerhans DC and B‐lymphocyte migration triggered by supernatants from IFI16‐overexpressing endothelial cells was partially inhibited by Ab inactivating CCL4, CCL5 and CCL20 chemokines. Altogether, these results demonstrate that the IFI16 gene, through its secretome, regulates proinflammatory activity of endothelial cells, thus corroborating its role in the early steps of inflammation.