bluuebunny/crossref_metadata_2025 huggingface dataset:
Ion Channel Regulation by Ras, Rho, and Rab Small GTPases
Authors: Pochynyuk Oleh , Stockand James D. , Staruschenko Alexander
Published: May 2008

Regulation of ion channels by heterotrimeric guanosine triphosphatases (GTPases), activated by heptathelical membrane receptors, has been the focus of several recent reviews. In comparison, regulation of ion channels by small monomeric G proteins, activated by cytoplasmic guanine nucleotide exchange factors, has been less well reviewed. Small G proteins, molecular switches that control the activity of cellular and membrane proteins, regulate a wide variety of cell functions. Many upstream regulators and downstream effectors of small G proteins now have been isolated. Their modes of activation and action are understood. Recently, ion channels were recognized as physiologically important effectors of small GTPases. Recent advances in understanding how small G proteins regulate the intracellular trafficking and activity of ion channels are discussed here. We aim to provide critical insight into physiological control of ion channel function and the biological consequences of regulation of these important proteins by small, monomeric G proteins.
Inflammation and Oxidative Stress in Obstructive Sleep Apnea Syndrome
Authors: Selmi Carlo , Montano Nicola , Furlan Raffaello , Keen Carl L. , Gershwin M. Eric
Published: May 2008

Similar to obesity, with which it is closely associated, obstructive sleep apnea syndrome (OSAS) is rapidly becoming a worldwide epidemic. Current knowledge of its pathogenesis has been significantly enriched by numerous experimental studies that have demonstrated an important role of oxidative stress and inflammation. Furthermore, new and exciting data strongly connect these two components in the perpetuation of the condition via the overexpression of nuclear factor κB. Experimental data support the hypothesis that nutrition might represent a promising future approach with antioxidants currently being good candidates for the modulation of cardiovascular sequelae, although weight reduction and controlled positive airway pressure remain the only established treatments for OSAS. We discuss herein the recent literature that illustrates these new paradigms and speculate on possible implications and future scenarios.
A BRIEF COMMUNICATION
Authors: Li Weiguo , Ota Kimiko , Nakamura Jiro , Naruse Keiko , Nakashima Eitaro , Oiso Yutaka , Hamada Yoji
Published: May 2008

Gliclazide, a sulfonylurea widely used for treatment of diabetes mellitus, is known to scavenge reactive oxygen species. To clarify whether its antioxidative ability interferes with the glycation processes, we incubated bovine serum albumin (BSA) with 1 M glucose or 1 m M methylglyoxal, in the presence or absence of gliclazide, and observed the formation of advanced glycation end products (AGEs). AGE production was assessed by AGE-specific fluorescence, an enzyme-linked immunosorbent assay (ELISA), and Western blotting. The fluorescence at excitation/emission wavelengths of 320/383 nm and 335/385 nm was definitely increased by incubating BSA with 1 M glucose or 1 m M methylglyoxal, and 1 m M gliclazide significantly blunted the fluorescent augmentation, in both wavelengths, in a dose-dependent fashion. Gliclazide almost equaled to aminoguanidine, a putative antiglycation agent, in the inhibitory effect on the glucose-induced fluorescence, while the methylglyoxal-derived fluorescent formation was less suppressed by gliclazide than by aminoguanidine. The AGE concentrations determined by ELISA showed similar results. Incubation of BSA with 1 M glucose or 1 m M methylglyoxal yielded an apparent increase in carboxymethyllysine or argpyrimidine. Both AGEs were significantly lowered by 1 m M gliclazide and a reduction of glucose-derived carboxymethyllysine was comparable to that caused by aminoguanidine. The results of Western blotting supported the findings in ELISA. To our knowledge, the present study provides the first evidence of the antiglycation effect of gliclazide on in vitro AGE formation from glucose and methylglyoxal.
Cholera Toxin Up-Regulates Endoplasmic Reticulum Proteins That Correlate with Sensitivity to the Toxin
Authors: Dixit Garima , Mikoryak Carole , Hayslett Tyler , Bhat Amritha , Draper Rockford K.
Published: May 2008

Cholera toxin (CT) contains one A chain and five B chains. The A chain is an enzyme that covalently modifies a trimeric G protein in the cytoplasm, resulting in the overproduction of cAMP. The B chain binds the glycosphingolipid GM1, the cell surface receptor for CT, which initiates receptor-mediated endocytosis of the toxin. After endocytosis, CT enters the endoplasmic reticulum (ER) via retrograde vesicular traffic where the A chain retro-translocates through the ER membrane to reach the cytoplasm. The retro-translocation mechanism is poorly understood, but may involve proteins of the ER stress response, including the ER associated degradation (ERAD) pathway. We report here that treating cells with CT or CTB quickly up-regulates the levels of BiP, Derlin-1, and Derlin-2, known participants in the ER stress response and ERAD. CT did not induce calnexin, another known responder to ER stress, indicating that the CT-mediated induction of ER proteins is selective in this time frame. These data suggest that CT may promote retro-translocation of the A chain to the cytoplasm by rapidly up-regulating a set of ER proteins involved in the retro-translocation process. In support of this idea, a variety of conditions that induced BiP, Derlin-1, and Derlin-2 sensitized cells to CT and conditions that inhibited their induction de-sensitized cells to CT. Moreover, specifically suppressing Derlin-1 with siRNA protected cells from CT. In addition, Derlin-1 co-immunoprecipitated with CTA or CTB from CT-treated cells using anti-CTA or anti-CTB antibodies. Altogether, the results are consistent with the hypothesis that the B chain of CT up-regulates ER proteins that may assist in the retro-translocation of the A chain across the ER membrane.
Angiotensin-Converting Enzyme Gene Polymorphism Is Associated with Anemia in Non–Small-Cell Lung Cancer
Authors: Yaren Arzu , Oztop Ilhan , Turgut Sebahat , Turgut Gunfer , Degirmencioglu Serkan , Demirpence Mustafa
Published: May 2008

The angiotensin-converting enzyme (ACE) plays an important role not only in the regulation of vascular homeostasis but also in stimulation of hematopoiesis. We aimed to evaluate the association between insertion/deletion (I/D) polymorphism of the ACE gene and anemia at the time of the diagnosis. We enrolled 75 patients with non–small-cell lung cancer (NSCLC) and 85 age- and sex-matched healthy control participants. The I/D polymorphism of ACE was identified by using polymerase chain reaction from peripheral blood samples. Statistical analyses were performed with SPSS for Windows. The distributions of the ACE genotypes and alleles are similar in patients and in healthy participants ( P = 0.29 and P = 0.08, respectively). In patients with NSCLC, 34 (45.3%) had anemia; of whom 3 (8.8%) had genotype II, 24 (70.6%) had genotype ID, and 7 (20.6%) had genotype DD ( P = 0.001). The patients with the II and ID genotypes had more frequent anemia at the time of the diagnosis (odds ratio = 6.02; P = 0.001). Our findings suggest that I/D polymorphism of the ACE gene may influence the development of anemia in patients with NSCLC.
Doxycycline Influences Microcirculation Patterns in B16 Melanoma
Authors: Sun Baocun , Zhang Shiwu , Zhang Danfang , Yin Xiaojin , Wang Sen , Gu Yanjun , Wang Yalei
Published: May 2008

To examine the effects of doxycycline on invasion-related protein expression and proliferation of melanoma cells and to evaluate its effect on microcirculation patterns in melanoma, we injected murine melanoma B16 cell suspensions into the groin areas of C57BL/6 mice that were randomly divided into treatment and control groups. Eight days after tumor cell injection, we administered doxycycline intraperitoneally (ip) at a dose of 0.15 mg/g/day in the treatment group and administered a physiological saline solution to the control group. Animals were sacrificed on Day 22, and we removed and weighed tumor masses and counted the numbers of vasculogenic mimicry (VM) and endothelium-dependent vessels. Immunohistochemical staining was used to analyze the expression of matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-9 (MMP-9), vascular endothelial growth factor (VEGF), and proliferating cell nuclear antigen (PCNA). We prepared protein extracts of the tumors, and we examined the activity of MMP-2 and MMP-9 in different groups by gelatin zymography. Real-time polymerase chain reaction (PCR) was used to detect MMP-2 and MMP-9 mRNA level in the fresh tumor tissue. Doxycycline treatment partly suppressed the growth of engrafted B16 melanoma, with an inhibition rate of 35.63%. There were more VM and endothelium-dependent vessels in the control group than in the treatment group. The expression level of MMP-2 and MMP-9 in the treatment group was lower than that in the control group ( P < 0.01, P < 0.05). Compared with the control group, VEGF expression was increased with doxycycline treatment. The enzyme activities of MMP-9, active-MMP-2, and MMP-2/pro-MMP-2 in the treatment group were lower than those in the control group ( P < 0.01). MMP-2 and MMP-9 mRNA levels in the treatment group were also lower than those in the control group were. Doxycycline inhibits the growth of engrafted melanoma and results in reduced expression of MMP-2, MMP-9, and VM formations.
The Human Red Blood Cell Proteome and Interactome
Authors: Goodman Steven R. , Kurdia Anastasia , Ammann Larry , Kakhniashvili David , Daescu Ovidiu
Published: May 2008

The red blood cell or erythrocyte is easily purified, readily available, and has a relatively simple structure. Therefore, it has become a very well studied cell in terms of protein composition and function. RBC proteomic studies performed over the last five years, by several laboratories, have identified 751 proteins within the human erythrocyte. As RBCs contain few internal structures, the proteome will contain far fewer proteins than nucleated cells. In this minireview, we summarize the current knowledge of the RBC proteome, discuss alterations in this partial proteome in varied human disease states, and demonstrate how in silico studies of the RBC interactome can lead to considerable insight into disease diagnosis, severity, and drug or gene therapy response. To make these latter points we focus on what is known concerning changes in the RBC proteome in Sickle Cell Disease.
Retinoid-Mediated Regulation of Mood: Possible Cellular Mechanisms
Authors: O’Reilly Kally , Bailey Sarah J. , Lane Michelle A.
Published: May 2008

Vitamin A and its derivatives, the retinoids, have long been studied for their ability to alter central nervous system (CNS) development. Increasingly, it is recognized that sufficient levels of retinoids may also be required for adult CNS function. However, excess dietary vitamin A, due to the consumption of supplements or foods rich in vitamin A, has been reported to induce psychosis. In addition, 13- cis-retinoic acid (13- cis-RA, isotretinoin), the active ingredient in the acne treatment Accutane, has been reported to cause adverse psychiatric events, including depression and suicidal ideation. Nevertheless, epidemiological studies have reported no consistent link between Accutane use and clinical depression in humans. Using an animal model, we have recently shown that 13- cis-RA induces an increase in depression-related behavior. Impairments in spatial learning and memory have also been demonstrated following 13- cis-RA treatment in mice. This review focuses on the behavioral and possible cellular effects of retinoid deficiency or excess in the adult brain in relation to altered mood. Specifically, we discuss the effect of retinoids on depression-related behaviors and whether norepinephrinergic, dopaminergic, or serotonergic neurotransmitter systems may be impaired. In addition, we consider the evidence that adult neurogenesis, a process implicated in the pathophysiology of depression, is reduced by retinoid signaling. We suggest that 13- cis-RA treatment may induce depression-related behaviors by decreasing adult neurogenesis and/or altering the expression of components of serotonergic neurotransmitter system, thereby leading to impaired serotonin signaling.
Erythropoietin Pretreatment Protects Against Acute Chemotherapy Toxicity in Isolated Rat Hearts
Authors: Ramond Amandine , Sartorius Eugénie , Mousseau Mireille , Ribuot Christophe , Joyeux-Faure Marie
Published: May 2008

The use of chemotherapeutic agents, such as anthracycline or trastuzumab, in oncology is limited by their cardiac toxicity. Recent experimental studies suggest that recombinant human erythropoietin (rhEPO) can be considered as a protective agent because its administration protects against cardiac ischemic injury, improving functional recovery, and reducing cell death. The aim of this study was to investigate whether pretreatment by rhEPO protects against acute cardiotoxicity induced by doxorubicin and trastuzumab, using the isolated rat heart model. Rats were treated with rhEPO (5000 IU/kg, intraperitoneally [ip]) or vehicle. One hour later, hearts were isolated and retrogradely perfused at constant flow. Following 20 mins of stabilization, hearts were perfused for 60 mins with modified-Krebs solution containing 6 mg/l doxorubicin or 10 mg/l trastuzumab. Hearts receiving doxorubicin were paced; those receiving trastuzumab were unpaced. Control hearts were perfused with modified-Krebs solution only. Doxorubicin exposure decreased left ventricular developed pressure (LVDP; approximately −40% of baseline) and increased end diastolic pressure (EDP; approximately +390% of baseline) and coronary perfusion pressure (CPP; approximately +70% of baseline). Incidence of ventricular tachycardia or fibrillation (VT/VF) was also significantly enhanced (86% vs. 0% in control group). Trastuzumab exposure increased CPP and EDP (approximately +70% of baseline for the both) without affecting LVDP. Prior rhEPO treatment significantly prevented doxorubicin-induced deleterious effects on LVDP, EDP, and VT/VF incidence. rhEPO administration also prevented trastuzumab-induced deleterious effects on CPP and EDP. This study shows that pretreatment by rhEPO protects myocardium against functional damage and electrophysiologic injury induced by acute doxorubicin or trastuzumab exposure. Further investigations are required to elucidate the precise mechanisms involved.
Mitochondrial Dysfunction and Redox Signaling in Atrial Tachyarrhythmia
Authors: Bukowska Alicja , Schild Lorenz , Keilhoff Gerburg , Hirte Daniel , Neumann Manfred , Gardemann Andreas , Neumann Klaus Hinrich , Röhl Friedrich-Wilhelm , Huth Christof , Goette Andreas , Lendeckel Uwe
Published: May 2008

Accumulating evidence links calcium-overload and oxidative stress to atrial remodeling during atrial fibrillation (AF). Furthermore, atrial remodeling appears to increase atrial thrombogeneity, characterized by increased expression of adhesion molecules. The aim of this study was to assess mitochondrial dysfunction and oxidative stress–activated signal transduction (nuclear factor-κB [NF-κB], lectin-like oxidized low-density lipoprotein receptor [LOX-1], intercellular adhesion molecule-1 [ICAM-1], and hemeoxgenase-1 [HO-1]) in atrial tissue during AF. Ex vivo atrial tissue from patients with and without AF and, additionally, rapid pacing of human atrial tissue slices were used to study mitochondrial structure by electron microscopy and mitochondrial respiration. Furthermore, quantitative reverse transcription polymerase chain reaction (RT-PCR), immunoblot analyses, gel-shift assays, and enzyme-linked immunosorbent assay (ELISA) were applied to measure nuclear amounts of NF-κB target gene expression. Using ex vivo atrial tissue samples from patients with AF we demonstrated oxidative stress and impaired mitochondrial structure and respiration, which was accompanied by nuclear accumulation of NF-κB and elevated expression levels of the adhesion molecule ICAM-1 and the oxidative stress-induced markers HO-1 and LOX-1. All these changes were reproduced by rapid pacing for 24 hours of human atrial tissue slices. Furthermore, the blockade of calcium inward current with verapamil effectively prevented both the mitochondrial changes and the activation of NF-κB signaling and target gene expression. The latter appeared also diminished by the antioxidants apocynin and resveratrol (an inhibitor of NF-κB), or the angiotensin II receptor type 1 antagonist, olmesartan. This study demonstrates that calcium inward current via L-type calcium channels contributes to oxidative stress and increased expression of oxidative stress markers and adhesion molecules during cardiac tachyarrhythmia.
Contribution of Fucose-Containing Capsules inKlebsiella pneumoniaeto Bacterial Virulence in Mice
Authors: Wu June Hsieh , Wu Albert M. , Tsai Cheng Gie , Chang Xin-Yu , Tsai Shih-Feng , Wu Ting-Shu
Published: May 2008

Bacterium Klebsiella pneumoniae (KP) contains a prominent capsule. Clinical infections usually are associated with pneumonia or urinary tract infection (UTI). Emerging evidence implicates KP in severe liver abscess especially in diabetic patients. The goal of this study was to investigate the capsular polysaccharides from KP of liver abscess (hepatic-KP) and of UTI-KP. The composition of capsular polysaccharides was analyzed by capillary high-performance liquid chromatography (HPLC, Dionex system). The terminal sugars were assayed by binding ability to lectins. The results showed that the capsule of a hepatic KP (KpL1) from a diabetic patient contained fucose, while the capsule from UTI-KP (KpU1) did not. The absence of fucose was verified by the absence of detectable polymerase chain reaction (PCR) fragment for fucose synthesis genes, gmd and wcaG in KpU1. Mice infected with the KpL1 showed high fatality, whereas those infected with the KpU1 showed high survival rate. The KpL1 capsule was reactive to lectins AAA and AAL, which detect fucose, while the KpU1 capsule was reactive to lectin GNA, which detects mannose. Phagocytosis experiment in mouse peritoneal cavity indicated that the peritoneal macrophages could interact with KpU1, while rare association of KpL1 with macrophages was observed. This study revealed that different polysaccharides were displayed on the bacterial capsules of virulent KpL1 as compared with the less virulent KpU1. Interaction of KpU1 with mice peritoneal macrophages was more prominent than that of KpL1. The possession of fucose might contribute to KpL1 virulence by avoiding phagocytosis since fucose on bacteria had been implicated in immune evasion.
Paradigm Shifts in Cancer Vaccine Therapy
Authors: Schlom Jeffrey , Gulley James L. , Arlen Philip M.
Published: May 2008

Cancer vaccines constitute a unique therapeutic modality in that they initiate a dynamic process involving the host’s immune response. Consequently, (a) repeated doses (vaccinations) over months may be required before patient clinical benefit is observed and (b) there most likely will be a “dynamic balance” between the induction and maintenance of host immune response elements to the vaccinations vs. host/tumor factors that have the potential to diminish those responses. Thus “patient response” in the form of disease stabilization and prolonged survival may be more appropriate to monitor than strictly adhering to “tumor response” in the form of Response Criteria In Solid Tumors (RECIST) criteria. This can be manifested in the form of enhanced patient benefit to subsequent therapies following vaccine therapy. This article will review these phenomena unique to cancer vaccines with emphasis on prostate cancer vaccines as a prototype for vaccine therapy. The unique features of this modality require the consideration of paradigm shifts both in the way cancer vaccine clinical trials are designed and in the way patient benefit is evaluated.
Upregulation of Macrophage Migration Inhibitory Factor (MIF) and CD74, Receptor for MIF, in Rat Bladder During Persistent Cyclophosphamide-Induced Inflammation
Authors: Vera Pedro L. , Wang Xihai , Meyer-Siegler Katherine L.
Published: May 2008

The objective of this study was to determine if macrophage migration inhibitory factor (MIF) is upregulated in the bladder during persistent cystitis. MIF is a pro-inflammatory cytokine found pre-formed in the urothelium. Previous findings showed that acute bladder inflammation increased MIF release into the bladder lumen while upregulating MIF and CD74 (MIF receptor) in the bladder. Because the effects of persistent cystitis on MIF and CD74 are not known, MIF and CD74 changes in the bladder were examined after short-term (1-day) or persistent (8-day) cyclophosphamide (CYP)-induced bladder inflammation. Anesthetized male Sprague-Dawley rats received either a single CYP treatment (150 mg/kg, ip; saline, control) and examined 1 day after treatment (short-term), or repeated CYP doses (20–75 mg/ kg, ip; saline, control; every third day for 8 days) and examined after 8 days of treatment (persistent). MIF protein levels in urine and bladder were determined. In addition, Mif, CD74, and cox-2 expression in the bladder was determined. Histology verified cystitis and MIF and CD74 immunoreactivity in the bladder. Repeated CYP doses were decreased to avoid toxicity. Short-term or repeated low CYP doses (40 mg/kg; 8 days) increased urinary MIF and decreased bladder MIF amounts while upregu-lating bladder Mif and CD74 mRNA expression. Persistent CYP-induced bladder inflammation (even at 40 mg/kg; 8-day treatment) also upregulated other inflammatory cytokines (CCL5, IL-11, iNOS) in the bladder. Short-term and persistent (low dose) CYP cystitis are associated with markedly increased MIF release into the urine and upregulation of Mif and CD74 in bladder. This supports the hypothesis that MIF and CD74 play a significant role in both acute and persistent stages of bladder inflammation.
β2-Microglobulin Deficient Mice Catabolize IgG More Rapidly Than FcRn-α-Chain Deficient Mice
Authors: Kim Jonghan , Bronson C. L. , Wani Manzoor A. , Oberyszyn Tatiana M. , Mohanty Sudhasri , Chaudhury Chaity , Hayton William L. , Robinson John M. , Anderson Clark L.
Published: May 2008

FcRn, a nonclassical MHC-I protein bound to β2-microglobulin (β2m), diverts IgG and albumin from an intracellular degradative fate, prolonging the half-lives of both. While knockout mouse strains lacking either FcRn-α-chain (AK) or β2m (BK) show much shorter half-lives of IgG and albumin than normal mice, the plasma IgG half-life in the BK and AK strains is different, being shorter in the BK strain. Since β2m does not affect the IgG production rate, we tested whether an additional β2m-associated mechanism protects IgG from catabolism. First, we compared the fractional disappearance rate in plasma of an intravenous dose of radioiodinated IgG in a mouse strain deficient in both FcRn-α-chain and β2m (ABK), in the two parental knockout strains (AK and BK), and in the background wild-type (WT) strain. We found that IgG survived longer in the β2m-expressing AK strain than in the β2m-lacking ABK and BK strains, whereas the IgG half-lives between the ABK and BK strains were identical. Then we compared endogenous concentrations of four typical plasma proteins among the four strains and found that steady-state plasma concentrations of both IgG and albumin were higher in the AK strain than in either the BK or the ABK strain. These results suggest that a β2m-associated effect other than FcRn prolongs the survival of both IgG and albumin, although leaky gene transcription in the AK strain cannot be ruled out.
Characteristics of Catechin- and Theaflavin-Mediated Cardioprotection
Authors: Dreger Henryk , Lorenz Mario , Kehrer Alexandra , Baumann Gert , Stangl Karl , Stangl Verena
Published: May 2008

Catechins and theaflavins–the main polyphenolic substances of green and black tea, respectively–exert a plethora of beneficial effects on the cardiovascular system. In a model of H2O2-mediated oxidative stress, we investigated the effects of epigallocatechin-3-gallate (EGCG) and theaflavin-3,3′-digallate (TF3) on neonatal rat cardiomyocytes. Pretreatment with EGCG or TF3 1 hr prior to induction of oxidative stress by H2O2 effectively protected cardiac myocytes as determined by measuring release of lactate dehydrogenase after 24 hrs. Longer pre-incubation times resulted in significant loss of protection. To enable further mechanistic insight, we investigated expression of antioxidative enzymes and activation of prosurvival signaling cascades. Whereas mRNA levels of glutathione peroxidase 3, superoxide dismutase 1, and catalase were not influenced by both polyphenols, heme oxygenase (HO-1) was selectively upregulated by EGCG—but not by TF3. However, inhibition of HO-1 did not diminish polyphenol-mediated cardioprotection. While EGCG and TF3 activated Akt, extracellular signal-regulated kinase 1/2, and p38 mitogen-activated protein kinase, inhibition of these kinases did not attenuate polyphenol-mediated protection. Loading of cardiomyocytes with dichlorofluorescein revealed that intracellular levels of reactive oxygen species were significantly reduced after treatment with EGCG or TF3 as early as 30 mins after induction of oxidative stress. In conclusion, activation of prosurvival signaling kinases and upregulation of antioxidative enzymes do not play a major role in tea polyphenol-mediated cardioprotection.
Adaptive input‐to‐output stabilization of nonlinear systems
Authors: Efimov D. V. , Fradkov A. L.
Published: May 2008

The problem of adaptive asymptotic stabilization of a set for nonlinear convexly parameterized dynamical systems is considered. The main result provides a framework for adaptive input‐to‐output stabilization theory in the presence of disturbances. Copyright © 2008 John Wiley & Sons, Ltd.
Specialized use of two fingers in free‐ranging aye‐ayes (Daubentonia madagascariensis)
Authors: Lhota Stanislav , Jůnek Tomáš , Bartoš Luděk , Kuběna Aleš A.
Published: May 2008

The aye‐aye (Daubentonia madagascariensis) possesses a highly specialized hand with two fingers, the third and the fourth, being used in a way unparalleled by any other primate. We observed the use of the third and the fourth fingers in various activities in four free‐ranging aye‐ayes. We found that the thin third finger was used exclusively or preferably for tapping, inserting into the mouth (probably for cleaning the teeth) and probing for nectar, kernels and insects in bamboo, twigs and live wood. In contrast, the robust fourth finger was used preferably when eating jackfruit (Artocarpus heterophyllus). When probing for invertebrates in soft plant tissues and in dead wood, both fingers were used in high proportions. To extract the contents from coconuts, the two fingers were apparently used for different tasks. From this small (686 observations), but unique, study of free‐ranging aye‐ayes, we conclude that the third finger appears to be specialized for use in tasks requiring high mobility, sensitivity and precision, whereas the fourth finger appears to be specialized for tasks requiring strength, scooping action and deep access. Am. J. Primatol. 70:786–795, 2008. © 2008 Wiley‐Liss, Inc.
Captive‐born cotton‐top tamarins (Saguinus oedipus) respond similarly to vocalizations of predators and sympatric nonpredators
Authors: Friant Sagan C. , Campbell Matthew W. , Snowdon Charles T.
Published: May 2008

What types of cues do callitrichid primates use to detect and respond to predators? Do they respond to predator‐specific cues or to more general cues? The evidence for these questions remains conflicting. We presented captive‐born and reared cotton‐top tamarins with no previous exposure to predators (or predator cues) with vocalizations from three potential predators of cotton‐top tamarin in the wild (white hawk, jaguar, and tayra) and with vocalizations from sympatric nonpredators (black‐faced antthrush and red howler monkey). Vocalizations from predators and from nonpredator mammals elicited equivalent arousal, fear, and vocal responses. Howler monkey roars produced the strongest responses. The results suggest that predator‐naïve cotton‐top tamarins do not recognize specific predator vocalizations, but may respond to vocal qualities (low‐frequency, noisy sounds) that indicate large body size, threat, or aggression. On the other hand, tamarins responded much more strongly to the higher frequency calls from the hawk than the antthrush, suggesting another mechanism must also be involved. The failure of captive‐reared tamarins to distinguish between vocalizations of predators and nonpredator mammals has important implications for reintroduction studies. Am. J. Primatol. 70:707–710, 2008. © 2008 Wiley‐Liss, Inc.
Heterogeneous polymeric reaction under shear flow
Authors: Xie Fan , Zhou Chixing , Yu Wei , Liu Jianye
Published: May 2008

The effects of different shear flows on polymeric reaction between poly(styrene/maleic anhydride) (SMA) and polyamide 6 (PA6) in heterogeneous blending system were investigated. FTIR, SEM, rheometry, and GPC were used to qualitatively analyze the reaction, and the reaction apparent activation energy was determined as 75.7 kJ/mol by a rheological method. To study the effects of different shear flows on heterogeneous polymeric reaction, a more practical technique was developed to select the data that only responds to the reaction without the effect of different shear flows. Avrami's equation was employed to analyze the reaction process under shear flow and the results showed that the half period (t1/2) of reaction process decreased with the increase of the shear rate in this study. Moreover, the decease rates were different in the different shear modes as follows: the half period decreased slightly under the oscillatory shear, whereas it decreased strongly under the steady shear. The possible reasons for these phenomena were discussed. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2008
Thermal characterization of poly(vinyl chloride) samples prepared by living radical polymerization: Comparison with poly(vinyl chloride) prepared by free radical polymerization
Authors: Coelho Jorge F. J. , Simões P. N. , Mendonça Patrícia V. , Fonseca A. C. , Gil M. H.
Published: May 2008

Poly(vinyl chloride) (PVC) samples were synthesized by a living radical polymerization (LRP) method and compared with commercial PVC prepared by the conventional free radical polymerization (FRP). The differences were assessed, for the first time, in terms of viscosimetry parameters and thermal analysis. The LRP method used to prepare the PVC‐LRP samples is the only one available to obtain this polymer free of structural defects, being of commercial interest in a view of preparing a new generation of PVC‐based polymer with outstanding performance. The polymerization temperature selected (35°C) to prepare the LRP samples is currently used in the industry to prepare PVC‐FRP grades with moderate to high molecular weight. Since the thermal stability is a direct consequence of the polymer structure, this study is of vital importance to understand the potential of new PVC‐LRP. The thermoanalytical measurements demonstrate an enhanced thermal stability of PVC‐LRP when compared with its FRP counterpart. The PVC‐LRP sample with very low molecular weight reveals a higher thermal stability than the most stable PVC‐FRP sample. It is the first report dealing with thermal analysis of PVC prepared by LRP. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2008
Macromolecularly imprinted calcium phosphate/alginate hybrid polymer microspheres with the surface imprinting of bovine serum albumin in inverse‐phase suspension
Authors: Zhao Kongyin , Huang Jianjun , Ying Xiaoguang , Cheng Guoxiang
Published: May 2008

Macromolecularly imprinted calcium phosphate/alginate hybrid polymer microspheres surface imprinted with bovine serum albumin were prepared in inverse‐phase suspension by introducing the intermixture solutions of bovine serum albumin (BSA) and CaCl2 in sodium alginate aqueous solution where (NH4)2HPO4 was added beforehand. Morphology of the imprinted microspheres was observed by optical microscopy. Rebinding dynamic and thermodynamic behaviors of surface molecularly imprinted calcium phosphate/alginate polymer microspheres (CP/A SMIPMs) and embedding molecularly imprinted calcium phosphate/alginate polymer microspheres (CP/A EMIPMs) were evaluated. CP/A SMIPMs exhibited significant improvement in equilibrium rebinding capacity (Qe) and imprinting efficiency (IE), compared to CP/A EMIPMs. The surface of CP/A SMIPMs was more competent to facilitate the migration and re‐assembling of proteins. Surface specific peak and interior specific peak were proposed to describe the characteristics of surface and interior specific rebinding behaviors in rebinding dynamics. The effects of (NH4)2HPO4 addition were investigated in detail, along with the concentration of sodium alginate and CaCl2 solutions to the rebinding and imprinting property of imprinted microspheres. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2008
Enantiomerically pure quaternary ammonium salts with a chiral alkyl chain N(CH3)(n‐C3H7)2(sec‐C4H9)I: Synthesis and physical studies
Authors: Gheorghe Ruxandra , Chamoreau Lise‐Marie , Kapitan Josef , Ovanesyan Nikolaï S. , Aldoshin Sergei M. , Hecht Lutz , Barron Laurence D. , Train Cyrille , Gruselle Michel
Published: May 2008

A pair of enantiomerically pure quaternary ammonium salts with a chiral side chain, methyl‐(R)‐(1‐methylpropyl)di(n‐propyl)ammonium iodide 1 and methyl‐(S)‐(1‐methylpropyl)di(n‐propyl)ammonium iodide 2, and the related racemate, methyl‐(rac)‐(1‐methylpropyl)di(n‐propyl)ammonium iodide 3, were synthesized through a reductive alkylation procedure, starting from enantiomerically pure and, also, racemic forms of (rac)‐(1‐methylpropyl)amine. A spectroscopic chiroptical signature in solution was provided by the Raman optical activity spectra of compounds 1 and 2. The crystallographic structures of 1, 2, and 3 were examined by single crystal X‐ray diffraction. 1 crystallizes in the tetragonal space group P43212 (no. 96), a = b = 12.826 (2) Å, c = 17.730 (2) Å, V = 2916.9 (5) Å3, Z = 8, Flack coefficient 0.04 (2). 2 crystallizes in the tetragonal space group P41212 (no. 92), a = b = 12.842 (1) Å, c = 17.749 (2) Å, V = 2927.0 (5) Å3, Z = 8, Flack coefficient 0.05 (2). The crystal structures and space groups for 1 and 2 are enantiomorphs and the crystallographic investigation confirmed the absolute configuration of the stereocenter in both compounds. 3 crystallizes in the monoclinic space group P21/n(no. 14), a = 8.178 (1) Å, b = 14.309 (2) Å, c = 12.328 (2) Å, β = 96.811 (6)o, V = 1432.4 (2) Å3, Z = 4. Chirality, 2008. © 2008 Wiley‐Liss, Inc.
Compact optical cell system for vacuum ultraviolet absorption and circular dichroism spectroscopy and its application to aqueous solution sample
Authors: Tanaka Masahito , Yagi‐Watanabe Kazutoshi , Kaneko Fusae , Nakagawa Kazumichi
Published: May 2008

We have designed a compact optical cell for studying the absorption and circular dichroism (CD) of a solution sample in the vacuum ultraviolet (VUV) region using a temperature control unit. The cell size was 34 mm in diameter and 14 mm in length. Such compactness was obtained by coating the VUV scintillator onto the outside of the back window. Because this scintillator converts the transmitted VUV light to visible light, the outside of this cell is operated under atmospheric pressure. The temperature of the sample solution was maintained in the range of 5°C to 80°C using a temperature control unit with a Peltier thermoelectric element. Changes in the sample temperature were observed by monitoring the absorption intensity of water. Through the study of VUV‐CD spectra of ammonium camphor‐10‐sulfonate aqueous solutions and the transmitted spectrum of an empty cell, it was concluded that this cell unit has sufficient performance for use in VUV spectroscopy. Chirality, 2008. © 2008 Wiley‐Liss, Inc.
Histiocytoid Cardiomyopathy: A Mitochondrial Disorder
Authors: Finsterer Josef
Published: May 2008

Histiocytoid cardiomyopathy (HICMP) is a rare, genetic, cardiac disorder of infancy or childhood, predominantly affecting girls, and clinically manifesting as severe cardiac arrhythmias or dilated cardiomyopathy. Pathoanatomically, HICMP is characterized by subendocardial, epicardial, or valvular yellow‐tan nodules, which are histologically built up of abnormal Purkinje fibers and multiple, scattered clusters of histiocytoid myocytes, which are filled with an increased number of normal or abnormal mitochondria. Within the myocardium, yellowish areas with irregular outlines are found and are histologically built up of enlarged, polygonal, histiocyte‐like cells with foamy granular cytoplasm. Since HICMP is frequently found in patients with mitochondrial deoxyribonucleic acid (DNA) mutations, HICMP cardiomyocytes carry an increased number of normal or abnormal mitochondria, and may show markedly decreased succinate‐cytochrome c reductase or NADH‐cytochrome c reductase activity; HICMP should be regarded as mitochondrial cardiomyopathy. Copyright © 2008 Wiley Periodicals, Inc.
HMWMAP2: New perspectives on a pathway to dendritic identity
Authors: Farah Carole Abi , Leclerc Nicole
Published: May 2008

Neuronal polarity is established by the differentiation of two types of cytoplasmic processes: dendrites and the axon. These processes can be distinguished by their composition in microtubule‐associated proteins, the high molecular weight MAP2 proteins (HMWMAP2) being found in the dendrites and tau proteins in the axon. It is believed that the main contribution of HMWMAP2 to the acquisition and maintenance of dendrites is to promote microtubule assembly and stability. However, recent studies force us to enlarge our view on how HMWMAP2 might contribute to defining the role of the dendritic microtubules. The purpose of this article is to convey our view that HMWMAP2 are important players in defining the contribution of microtubules to dendritic identity by anchoring membranous organelles and signaling proteins to the dendritic microtubules and by being a receptor for neurosteroids. Cell Motil. Cytoskeleton 2008. © 2008 Wiley‐Liss, Inc.
Coordination of outer arm dynein activity along axonemal doublet microtubules
Authors: Seetharam Raviraja N. , Satir Peter
Published: May 2008

This study considers the mechanism by which ODA based sliding is produced and the relationship of that mechanism to the determination of beat frequency. Two models of activity have been examined: a stochastic model, where ODA activity is random and a metachronal model, where activity is sequentially triggered along a doublet. Inactivation of a few ODAs would have virtually no effect on stochastic activity, but would completely block metachronal activity. We (Seetharam and Satir [2005]: Cell Motil Cytoskeleton 60:96–103) previously demonstrated that ODAs produce high speed sliding of about 200 μm/s, followed by a pause. IDAs produce slow, 5 μm/s, continuous sliding. We have examined the effects of nM concentrations of vanadate on sliding, measuring velocity and extent of high speed sliding and pause distribution or sliding cessation. In 5 nM vanadate, where photocleavage experiments show about 16/270 ODAs per doublet are affected, no differences from control are seen, but at 10 and 25 nM vanadate, high speed velocity is greatly reduced and pause distribution changes. The results support a model, in which high speed sliding is produced by metachronal activity. Blockage of two or more heavy chains of one ODA or a small group of adjacent ODAs produces cessation of sliding, but cessation is only temporary, probably because IDA activity continues, allowing ODA activity re‐initiation beyond the block. These conclusions are consistent with Sugino and Naitoh's [1982; Nature 295:609–611] proposal, whereby during each beat, every ODA along a doublet becomes activated in succession, with repetitive activation determining beat frequency. Cell Motil. Cytoskeleton 2008. © 2008 Wiley‐Liss, Inc.
Validation by calibration of the UCLA integrated staging system prognostic model for nonmetastatic renal cell carcinoma after nephrectomy
Authors: Cindolo Luca , Chiodini Paolo , Gallo Ciro , Ficarra Vincenzo , Schips Luigi , Tostain Jacques , de La Taille Alexandre , Artibani Walter , Patard Jean Jacques
Published: May 2008

BACKGROUND.

To the authors' knowledge, calibration of the University of California at Los Angeles (UCLA) Integrated Staging System (UISS) prognostic score in patients nephrectomized for nonmetastatic renal cell carcinoma (RCC) has never been specifically addressed. The objective of the current study was to evaluate the calibration of the UISS prognostic score in a European multicenter retrospective study.

METHODS.

Six European centers participated in the study. According to the UISS, the endpoint was overall survival (OS). Survival curves were estimated by the Kaplan‐Meier method. For calibration assessment, the approach of ‘validation by calibration’ first proposed by Van Houwelingen was used. The original prognostic score is embedded in a ‘calibration model’ that allows testing, in the validation cohort, the baseline hazards function as well the model linear predictor. Estimates of the ‘calibration model’ were used to recalibrate the UISS score.

RESULTS.

Of the 2471 available subjects, 399 had died of any cause within the first 5 years. The observed OS curves were compared with the corresponding expected model‐based curves. The UISS model did not adequately predict OS, particularly in the extreme categories (P < .0001). Patients in the validation sample, indeed, fared systematically better than patients in the developing cohort. There was no evidence, instead, of a change in the relative effect of the prognostic covariates. After recalibration, the UISS score worked well in the validation cohort.

CONCLUSIONS.

The UISS score has good discrimination accuracy and is based on an adequately developed risk function. However, it systematically underestimates OS. At least in a European cohort of RCC patients, the use of the recalibrated UISS model could improve prediction accuracy. Cancer 2008. © 2008 American Cancer Society.
Distinctive E‐cadherin and epidermal growth factor receptor expression in metastatic and nonmetastatic head and neck squamous cell carcinoma
Authors: Muller Susan , Su Ling , Tighiouart Mourad , Saba Nabil , Zhang Hongzheng , Shin Dong M. , Chen Zhuo (Georgia)
Published: May 2008

BACKGROUND.

The authors investigated whether coexpression and localization of E‐cadherin (E‐cad) and epidermal growth factor receptor (EGFR) had predictive and/or prognostic correlations with lymph node metastasis and/or survival in patients with squamous cell carcinoma of the head and neck (SCCHN).

METHODS.

Immunohistochemistry (IHC) of archival tissue was performed to measure expression of EGFR and E‐cad in surgical specimens of SCCHN (n = 143) that included primary tumors (PTs) with positive lymph nodes (Tu+Met) and their paired lymph node metastases (LnMet), PTs with negative lymph nodes (Tu−Met), and benign tissue biopsies as normal controls. IHC staining was quantified as a weighted index and as the ratio of membrane to cytoplasmic staining. Correlative expression between EGFR and E‐cad also was examined in SCCHN cell lines by immunoblotting and immunofluorescence analyses.

RESULTS.

Three distinct expression patterns of EGFR and E‐cad were observed. Membrane localization of E‐cad was significantly lower in the Tu+Met group than in the Tu−Met group (P = .01) and was associated inversely with lymph node status (P = .009). Wilcoxon analysis of the combined markers demonstrated that expression and/or membrane localization of EGFR and E‐cad were correlated with disease‐free survival and overall survival in patients with SCCHN. The study of SCCHN cell lines demonstrated that cells with positive but low EGFR expression and with negative E‐cad expression were relatively resistant to the EGFR tyrosine kinase inhibitor erlotinib.

CONCLUSIONS.

The current study suggested that examining not only the expression but also the localization of EGFR and E‐cad simultaneously may have clinical relevance in predicting lymph node metastasis, patient survival, and response to EGFR‐targeted therapy in patients with SCCHN. Cancer 2008. © 2008 American Cancer Society.
Phase 1 study of XL119, a rebeccamycin analog, in patients with refractory hematologic malignancies
Authors: Borthakur Gautam , Alvarado Yesid , Ravandi‐Kashani Farhad , Cortes Jorge , Estrov Zeev , Faderl Stefan , Ivy Percy , Bueso‐Ramos Carlos , Nebiyou Bekele B. , Giles Francis
Published: May 2008

BACKGROUND.

XL119 is a water‐soluble derivative of rebeccamycin with dose‐dependent myelosuppression as dose‐limiting toxicity in phase 1 studies of solid tumors. A phase 1 study was conducted to determine the maximum tolerated dose and toxicities of XL119 in patients with advanced myelodysplastic syndrome and relapsed or refractory acute leukemias.

METHODS.

Thirty‐one patients were treated at 7 dose levels ranging from 140 to 260 mg/m2/daily times 5 in a 21‐day cycle. Consenting patients had correlative biologic parameters studied.

RESULTS.

Dose‐limiting toxicity was grade 3/4 mucositis. The recommended phase 2 dose in hematologic malignancies is 240 mg/m2/daily times 5 in a 21‐day cycle. Clinically significant reduction in bone marrow blasts were seen in 5 patients and additional patients had reductions in peripheral blood blasts. However, the responses were transient. Changes of plasma vascular endothelial growth factor levels from Day 1 to Day 7 correlated negatively with changes in peripheral blood blasts from Day 1 to Day 7.

CONCLUSIONS.

Further assessment of XL119 in combination with other agents in patients with acute leukemias and high‐risk myelodysplastic syndrome is warranted. Cancer 2008. Published 2008 by the American Cancer Society.
Neural architecture of the brachiolaria larva of the starfish, Asterina pectinifera
Authors: Murabe Naoyuki , Hatoyama Hideo , Hase Sumitaka , Komatsu Miéko , Burke Robert D. , Kaneko Hiroyuki , Nakajima Yoko
Published: May 2008

The nervous system of the brachiolaria larva of the starfish, Asterina pectinifera, was characterized using immunohistochemistry with the neuron‐specific monoclonal antibodies 1E11 and 1F9 and an anti‐serotonin antibody. The antigen recognized by 1F9 was determined by immunoprecipitation, peptide identification by mass spectrometry, and cDNA cloning as a novel START (steroidogenic acute regulatory protein [StAR]‐related lipid transfer) domain‐containing protein. Nerve cells are prominent in the brachiolar arms, ciliary bands, and adult rudiment. The brachiolar arms contain sensory‐like nerve cells in the adhesive papillae, flask‐shaped nerve cells in the adhesive disk, and bundles of fibers with branches interconnecting them. In the ciliary bands, nerve cells are interconnected with axon bundles along the ciliary bands and some neurons send fibers toward the oral and aboral epidermis. These neural components of the ciliary bands are regionally modified to form masses such as lateral and oral ganglia. The future aboral epidermis of the adult rudiment forms a nerve plexus with cell bodies enriched over spicules. Serotonergic nerve cell bodies are found throughout the nervous system except in the adhesive disk, the bipinnaria arms, and the adult rudiment. In addition, there are neural components in the esophagus and in the coelom where nerve fibers or bundles have distinct orientations with respect to the muscle fibers. The neuroanatomy of the brachiolaria suggests how it may function in controlling larval physiology and identifies intriguing problems on the origin of larval and adult nerves. J. Comp. Neurol. 509:271–282, 2008. © 2008 Wiley‐Liss, Inc.