bluuebunny/crossref_metadata_2025 huggingface dataset:
Rare genotype combination of the serotonin transporter gene associated with treatment response in severe personality disorder
Authors: Perroud Nader , Salzmann Annick , Saiz Pilar A. , Baca‐Garcia Enrique , Sarchiapone Marco , Garcia‐Portilla Maria P. , Carli Vladimir , Vaquero‐Lorenzo Concepción , Jaussent Isabelle , Mouthon Dominique , Vessaz Monique , Huguelet Philippe , Courtet Philippe , Malafosse Alain ,   and European Research Consortium for Suicide (EURECA)
Published: September 2010

The insertion deletion (ins/del) polymorphism of the serotonin transporter gene (5‐HTTLPR) has been associated with several psychiatric phenotypes and antidepressant's response. We investigated, in a large cohort of 5,608 controls and subjects suffering from various psychiatric disorders, the frequency of haplotypes and corresponding genotypes combining the 5‐HTTLPR and the other serotonin transporter promoter functional variant (rs25531). We showed that rs25531 lies 18 bp 5′ to the site where the 43 bp (and not 44 bp as previously described) ins/del defines the 14‐ and 16‐repeat alleles. These polymorphisms should therefore be considered as four alleles instead of a triallelic unique locus. The very rare G‐14/G‐16 genotype was carried on by only three subjects. These are women with a history of suicide attempt with a psychiatric history strongly suggesting a borderline personality disorder. Two of them have shown a non‐response to serotoninergic antidepressant. Interestingly, in one of them was observed a spectacular response after the introduction of bupropion. The genotyping droved our therapeutic approach, by preferring a dopaminergic over a serotoninergic agent. This study highlights the usefulness of studying very rare clinical cases as well as rare variants, in order to deal with the biological heterogeneity of spectral disorders. © 2010 Wiley‐Liss, Inc.
Compatibilization of polyethylene/polyaniline blends with polyethylene‐graft‐maleic anhydride
Authors: Del Castillo‐Castro T. , Castillo‐Ortega M. M. , Herrera‐Franco P. J. , Rodríguez‐Félix D. E.
Published: September 2010

The use of compatibilizers as interfacial agents in composites can offer a convenient way to improve the mechanical properties of immiscible polymer blends. The aim of this article is to illustrate the compatibilization effect of polyethylene‐graft‐maleic anhydride (PEgMA) in blends of low‐density polyethylene (LDPE) and n‐dodecylbenzene sulfonate doped polyaniline (PANIDBSA) prepared by extrusion. Films with different compositions of the coupling agent were evaluated with optical spectroscopy and thermomechanical, electrical, mechanical, and morphological techniques. The incorporation of PEgMA into the LDPE/PANIDBSA composites resulted in an improvement of their electrical conductivity and changes in the mechanical and morphological properties of the films. When 5 wt % of the coupling agent was added to a 30 wt % of the polyaniline‐containing film, the conductivity increased by more than three orders of magnitude, and the ductility also improved qualitatively. The morphology analysis also indicated that the addition of PEgMA produced a strengthening of the filler–matrix interfacial region. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2010
Thermal and flame retardant properties of ethylene‐vinyl acetate copolymer/modified multiwalled carbon nanotube composites
Authors: Wang Lichun , Jiang Ping Kai
Published: September 2010

The synthesized flame retardant 9,10‐dihydro‐9‐oxa‐10‐phosphaphanthrene‐10‐oxide/vinyl methyl dimethoxysilane (DV) was used to modify multiwalled carbon nanotubes (MWNTs). The results of FTIR, 1H‐NMR, and TGA measurements show that DV has been covalently grafted onto the surfaces of MWNTs, and the MWNTs‐g‐DV is obtained successfully. Transmission electron microscopy images show that a core‐shell nanostructure appears with MWNTs as the core and the DV thin layers as the shell, and the modified MWNTs with DV can achieve better dispersion than unmodified MWNTs in EVM matrix. Thermogravimetric analysis and cone calorimeter tests indicate that the thermal stability and flame retardant are improved for the presence of the MWNTs in EVM matrix. Moreover, the improvement is more evident for EVM/MWNTs‐g‐DV composite compared to unmodified MWNTs‐based composite, which can be attributed to the better dispersion of the DV‐modified MWNTs and to the chemical structure of the combustion residue. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2011
Polyvinylphosphonic acid copolymer hydrogels prepared with amide and ester type crosslinkers
Authors: Kusunoki Takayuki , Oshiro Masaru , Hamasaki Fumi , Kobayashi Takaomi
Published: September 2010

Crosslinked hydrogels made of poly(vinylphosphonic acid‐co‐N,N′‐methylenebisacrylamide) (P(VPA‐co‐MBAA)) and poly(vinylphosphonic acid‐co‐ethyleneglycol diacrylate) (P(VPA‐co‐EGDA)) were prepared by using precipitation polymerization in water medium. A comparison research was made between the resultant hydrogels containing different loads of vinylphosphonic acid segments when N,N′‐methylenebisacrylamide (MBAA) or ethyleneglycol diacrylate (EGDA) were used as comonomers. Morphological observations indicated that the resultant copolymer appeared as a fine powder at low VPA loadings and strongly aggregated at the high loadings; especially, a copolymer containing 63 mol % of VPA segments in P(VPA‐co‐MBAA) was observed to have a flake‐shaped appearance in its aggregated morphology. The resultant copolymer powders were characterized using FTIR spectroscopy and titrimetric analysis. Also, monomer reactivity ratios, r1 and r2, of VPA and MBAA or EGDA were estimated as 0.06 and 0.98 for VPA and MBAA and 0.05 and 1.82 for VPA and EGDA, respectively. This suggested that a large distribution of MBAA and EGDA was present in the resultant copolymer powders. Their crosslinked PVPA structure presented hydrogel properties having high water uptakes and an absorption mechanism independent from pH of bulk solution. The evidence showed that high VPA loadings could strongly interacted through hydrogen bonds between neighbor VPA segments even in the presence of water. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2010
Melt index prediction by RBF neural network optimized with an adaptive new ant colony optimization algorithm
Authors: Li Jiubao , Liu Xinggao
Published: September 2010

Melt index (MI) is a crucial indicator in determining the product specifications and grades of polypropylene (PP). The prediction of MI, which is important in quality control of the PP polymerization process, is studied in this work. Based on RBF (radial basis function) neural network, a soft‐sensor model (RBF model) of the PP process is developed to infer the MI of PP from a bunch of process variables. Considering that the PP process is too complicated for the RBF neural network with a general set of parameters, a new ant colony optimization (ACO) algorithm, N‐ACO, and its adaptive version, A‐N‐ACO, which aim at continuous optimizing problems are proposed to optimize the structure parameters of the RBF neural network, respectively, and the structure‐best models, N‐ACO‐RBF model and A‐N‐ACO‐RBF model for the MI prediction of propylene polymerization process, are presented then. Based on the data from a real PP production plant, a detailed comparison research among the models is carried out. The research results confirm the prediction accuracy of the models and also prove the effectiveness of proposed N‐ACO and A‐N‐ACO optimization approaches in solving continuous optimizing problem. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2010
Preparation and properties of unsaturated polyester nanocomposites based on silylated sepiolite nanofibers
Authors: Lu Panfang , Xu Jing , Liu Kaiping
Published: September 2010

The novel surface‐modified sepiolite/unsaturated polyester (sepiolite/UP) nanocomposites were prepared by in situ polymerization. Sepiolite fibers were first organo‐modified by grafting of vinyltriethoxysilane (VTS) containing a double bond onto the surfaces and used as nanofillers. The morphology of sepiolites and nanocomposites were characterized by X‐ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), scanning electron microscope (SEM), and transmission electron microscope (TEM). Moreover, the thermal properties were determined by thermogravimetric analysis (TGA) and the thermal degradation mechanism was discussed. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2010
Preparation, characterization, and swelling and drug release properties of a crosslinked chitosan‐polycaprolactone gel
Authors: Aroguz Ayse Z. , Baysal Kemal , Tasdelen Betul , Baysal Bahattin M.
Published: September 2010

For applications in biotechnology to prepare biopolymers containing functional groups is essential. In addition, these materials have to be strong to provide physical support for practical applications. Recently, chitosan, polycaprolactone (PCL), and their various combinations were used for this purpose. In this work, we described the preparation and characterization of a new biodegradable polymeric gel containing chitosan and PCL. The gel preparation reactions were performed in suitable acetic acid solutions to obtain the products in high yields. A crosslinking agent was added to produce crosslinked gels. Swelling behavior of chitosan/PCL gels in different compositions was studied, and the results were compared. The chitosan/PCL gels show a rather large equilibrium swelling in water and in the phosphate buffered saline solution. Acrylic acid (AA) was added to these gels during preparation process to obtain a stable material for various applications. These polymeric gels were characterized by Fourier transform infrared. Their physical and morphological properties were investigated by using differential scanning calorimeter and scanning electron microscope techniques, respectively. Cell growth experiments indicate that chitosan, a positively charged polysaccharide, is not suitable for cell proliferation studies. On the other hand, the drug release studies were successful and, 59% of lidocaine, was released from a chitosan/PCL/AA hydrogel in buffer solution at pH = 7.4 at 37°C. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2010
Intermolecular crosslinking of poly(acrylic acid) in aqueous solution by electron beam irradiation
Authors: Lappan Uwe , Uhlmann Steffi
Published: September 2010

Poly(acrylic acid) (PAA) was dissolved in water, and the solution was irradiated with high‐energy electrons. The formation of macroscopic gel was studied as a function of the radiation dose, the pH of the aqueous solution, and the concentration of added salt. Gelation by intermolecular crosslinking was found at low pH values of 2–4, whereas at pH greater or equal to 5, no gel was formed by electron beam irradiation. Nevertheless, by adding monovalent salt the gel formation was enhanced at intermediate pH values. The intermolecular crosslinking was assumed to be inhibited by electrostatic repulsive forces when the macromolecules of PAA are negatively charged and the ionic strength of the solution is low. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2010
Dichotomous response to transforming growth factor β after T cell receptor activation by naive CD4+ T cells from DBA/1 mice: Enhanced retinoic acid receptor–related orphan nuclear receptor γt expression yet reduced FoxP3 expression
Authors: Morita Yoshiaki , Ismail Doaa M. , Elkon Keith B. , Chu Cong‐Qiu
Published: September 2010

Objective

To investigate the molecular mechanism for biased interleukin‐17 (IL‐17) production by DBA/1 CD4+ T cells upon T cell receptor (TCR) and transforming growth factor β (TGFβ) stimulation.

Methods

Purified naive CD4+ T cells were stimulated with anti‐CD3/CD28 under Th1, Th2, Th17, and induced T regulatory (iTreg) cell conditions. Cytokine production was assayed by intracellular staining and enzyme‐linked immunosorbent assay. Expression of transcription factors was determined by reverse transcription–polymerase chain reaction, flow cytometry, and immunoblotting techniques.

Results

Naive CD4+ T cells from DBA/1 mice produced more IL‐17 under Th17 cell polarizing conditions as compared with those from C57BL/6 or BALB/c mice. Further investigation revealed no difference among the strains in terms of CD4+ T cell survival, upstream TCR signaling, or CD69 expression or in the phosphorylation of STAT‐3 and expression of suppressor of cytokine signaling 3 that positively or negatively regulate IL‐17 cell production. However, DBA/1 CD4+ T cells expressed increased levels of retinoic acid–related orphan receptor γt (RORγt). Furthermore, under iTreg cell polarizing conditions, DBA/1 CD4+ T cells showed a strikingly reduced level of FoxP3 expression. When interferon‐γ and IL‐4 were blocked, FoxP3 expression increased but remained lower in DBA/1 CD4+ T cells following exposure to TGFβ as compared with C57BL/6 CD4+ T cells. Moreover, DBA/1 CD4+ T cells showed reduced phosphorylation of Smad2 and Smad3 under both Th17 and iTreg cell polarizing conditions.

Conclusion

These results indicate that naive CD4+ T cells from DBA/1 mice have a dichotomous response to TGFβ: enhanced RORγt, yet reduced FoxP3, up‐regulation. This observation may help to elucidate the branch point of TGFβ signaling that leads to skewed Th17, but reduced iTreg, cell differentiation.
Contribution of H3K4 methylation by SET‐1A to interleukin‐1–induced cyclooxygenase 2 and inducible nitric oxide synthase expression in human osteoarthritis chondrocytes
Authors: El Mansouri Fatima Ezzahra , Chabane Nadir , Zayed Nadia , Kapoor Mohit , Benderdour Mohamed , Martel‐Pelletier Johanne , Pelletier Jean‐Pierre , Duval Nicolas , Fahmi Hassan
Published: September 2010

Objective

To investigate the role of histone H3 lysine 4 (H3K4) methylation in interleukin‐1β (IL‐1β)–induced cyclooxygenase 2 (COX‐2) and inducible nitric oxide synthase (iNOS) expression in human osteoarthritic (OA) chondrocytes.

Methods

Chondrocytes were stimulated with IL‐1, and the expression of iNOS and COX‐2 messenger RNA and proteins was evaluated by real‐time reverse transcriptase–polymerase chain reaction analysis and Western blotting, respectively. H3K4 methylation and the recruitment of the histone methyltransferases SET‐1A and MLL‐1 to the iNOS and COX‐2 promoters were evaluated using chromatin immunoprecipitation assays. The role of SET‐1A was further evaluated using the methyltransferase inhibitor 5′‐deoxy‐5′‐(methylthio)adenosine (MTA) and gene silencing experiments. SET‐1A level in cartilage was determined using immunohistochemistry.

Results

The induction of iNOS and COX‐2 expression by IL‐1 was associated with H3K4 di‐ and trimethylation at the iNOS and COX‐2 promoters. These changes were temporally correlated with the recruitment of the histone methyltransferase SET‐1A, suggesting an implication of SET‐1A in these modifications. Treatment with MTA inhibited IL‐1–induced H3K4 methylation as well as IL‐1–induced iNOS and COX‐2 expression. Similarly, SET‐1A gene silencing with small interfering RNA prevented IL‐1–induced H3K4 methylation at the iNOS and COX‐2 promoters as well as iNOS and COX‐2 expression. Finally, we showed that the level of SET‐1A expression was elevated in OA cartilage as compared with normal cartilage.

Conclusion

These results indicate that H3K4 methylation by SET‐1A contributes to IL‐1–induced iNOS and COX‐2 expression and suggest that this pathway could be a potential target for pharmacologic intervention in the treatment of OA and possibly other arthritic diseases.
Improved outcome in 445 patients with Wegener's granulomatosis in a German vasculitis center over four decades
Authors: Holle Julia U. , Gross Wolfgang L. , Latza Ute , Nölle Bernhard , Ambrosch Petra , Heller Martin , Fertmann Regina , Reinhold‐Keller Eva
Published: September 2010

Objective

To determine the long‐term outcome in patients with Wegener's granulomatosis (WG) over 4 decades in an academic hospital unit specializing in rheumatology.

Methods

We included 290 patients, divided them into 2 cohorts, and compared them with the historical cohort of 155 patients. Comparisons were retrospective regarding disease manifestations, therapy, mortality, and incidence of malignancies. The historical cohort (cohort 1) included 155 patients diagnosed between 1966 and 1993, cohort 2 included 123 patients diagnosed between 1994 and 1998, and cohort 3 included 167 patients diagnosed between 1999 and 2002.

Results

Over time, the interval between first symptoms and diagnosis was reduced by half (from 8 months to 4 months). Organ manifestations were similar in the 3 cohorts, and more than 80% of patients still required cyclophosphamide (CYC); however, the median cumulative dose was reduced significantly (from 67 gm in cohort 1 to 36 gm in cohort 2 and to 24 gm in cohort 3). The standardized mortality ratios (SMRs) declined (from 2.1 in cohort 1 to 1.41 in cohort 2 and to 1.03 in cohort 3), with fewer deaths related to WG and/or therapy (86.4% in cohort 1, 76.9% in cohort 2, 50% in cohort 3), decreasing relapse rates (63.9% in cohort 1, 51.2% in cohort 2, 35.3% in cohort 3), and no increased rate of malignancies. Compared with young females, young males had a considerably higher SMR (8.87 [95% confidence interval 4.05–16.8]) and more frequent renal manifestations (54.4% versus 33.8%).

Conclusion

Mortality of WG patients declined over the last 4 decades, probably due to improved diagnostic and therapeutic procedures and increased awareness of WG, which led to earlier diagnosis and therapy, reduction in relapse rates, and lower cumulative CYC dose with fewer deaths related to therapy.
Anatomical Sciences Education Vol.3, Issue 5, 2010 Cover Image
Authors: Skinder‐Meredith Amy E.
Published: September 2010

Speech and Hearing Science students at Washington State University are shown drawing the bones and muscles involved in respiration on t‐shirts worn by their classmates. In this issue of ASE, Dr. Skinder‐Meredith shares a variety of multimodal learning activities she uses to help her students learn about anatomy during the physiological functions of respiration, phonation, articulation, resonance, and swallowing.
Randomized clinical trial of Chinese herbal medications to reduce wound complications after mastectomy for breast carcinoma
Authors: Chen J , Lv Q , Yu M , Zhang X , Gou J
Published: September 2010

Background

Ischaemia and necrosis of skin flaps is a common complication after mastectomy. This study evaluated the influence of anisodamine and Salvia miltiorrhiza on wound complications after mastectomy for breast cancer.

Methods

Ninety patients undergoing mastectomy for breast carcinoma were divided into three groups. Group 1 received routine wound care, group 2 received intravenous Salvia miltiorrhiza after surgery for 3 days and group 3 similarly received intravenous anisodamine. Skin flaps were observed on postoperative days 4 and 8; areas of wound ischaemia and necrosis were graded and adverse events recorded.

Results

There was no difference in demographic characteristics between the groups. At 4 days after surgery the rate of ischaemia and necrosis in groups 2 and 3 was significantly reduced compared with that in control group 1 (median wound score 6·80 versus 23·38, P = 0·002, and 3·76 versus 23·38, P < 0·001, respectively). This improvement in groups 2 and 3 continued to postoperative day 8 (both P < 0·001), but wound scores at this stage were better in group 3 than in group 2 (1·82 versus 6·92 respectively; P = 0·022). The volume of wound drainage was lower in group 3 than in group 1 (P = 0·004). The incidence of adverse effects was highest in group 3, and two patients in this group discontinued treatment. No significant complications were noted in group 2.

Conclusion

Anisodamine and S. miltiorrhiza were both effective in reducing skin flap ischaemia and necrosis after mastectomy, although anisodamine was associated with a higher rate of adverse effects.
Renal cytokines improve early after bariatric surgery
Authors: Bueter M , Dubb S S , Gill A , Joannou L , Ahmed A , Frankel A H , Tam F W K , le Roux C W
Published: September 2010

Background

Bariatric surgery has been suggested to improve arterial hypertension and renal function. This prospective controlled observational study aimed to investigate changes in renal inflammation, renal function and arterial blood pressure before and after bariatric surgery.

Methods

Blood pressure was measured, and urine and blood samples were collected from 34 morbidly obese patients before and 4 weeks after bariatric surgery. Serum levels of cystatin C, creatinine, albumin, cholesterol and C-reactive protein (CRP) were measured, along with urinary cytokine/creatinine ratios for macrophage migration inhibitory factor (MIF), monocyte chemotactic protein (MCP) 1, chemokine ligand (CCL) 18 and CCL-15.

Results

Mean(s.e.m.) bodyweight dropped from 124·1(2·6) to 114·8(2·4) kg (P < 0·001) and mean arterial blood pressure decreased from 105·7(1·8) to 95·5(1·2) mmHg (P < 0·001) in 4 weeks. Systemic and urinary inflammatory markers improved, with a reduction in serum CRP level (P < 0·001), and decreased urinary MIF/creatinine (P < 0·001), MCP-1/creatinine (P < 0·001) and CCL-18/creatinine (P = 0·003) ratios. In contrast, urinary CCL-15/creatinine ratios did not change and the glomerular filtration rate, measured by serum cystatin C, was unchanged (P = 0·615).

Conclusion

Surgically induced weight loss contributed to a decrease in blood pressure and markers of renal inflammation. The reduced levels of CRP and urinary cytokines suggest that bariatric surgery attenuates systemic and renal inflammatory status.
Differential sublocalization of actin variants within the nucleus
Authors: Kandasamy Muthugapatti K. , McKinney Elizabeth C. , Meagher Richard B.
Published: September 2010

Conventional actin has been implicated in various nuclear processes including chromatin remodeling, transcription, nuclear transport, and overall nuclear structure. Moreover, actin has been identified as a component of several chromatin remodeling complexes present in the nucleus. In animal cells, nuclear actin exists as a dynamic equilibrium of monomers and polymers. Actin‐binding proteins (ABPs) such as ADF/cofilin and profilin play a role in actin import and export, respectively. However, very little is known about the localization and roles of nuclear actin in plants. In multicellular plants and animals, actin is comprised of an ancient and divergent family of protein variants. Here, we have investigated the presence and differential localization of two ancient subclasses of actin in isolated Arabidopsis nuclei. Although the subclass 1 variants ACT2 and ACT8 and subclass 2 variant ACT7 were found distributed throughout the nucleoplasm, ACT7 was often found more concentrated in nuclear speckles than subclass 1 variants. The nuclei from the act2‐1/act8‐2 double null mutant and the act7‐5 null mutant lacked their corresponding actin variants. In addition, serial sectioning of several independent nuclei revealed that ACT7 was notably more abundant in the nucleolus than the subclass 1 actins. Profilin and ADF proteins were also found in significant levels in plant nuclei. The possible functions of differentially localized nuclear actin variants are discussed. © 2010 Wiley‐Liss, Inc.
Assembly of filopodia by the formin FRL2 (FMNL3)
Authors: Harris Elizabeth S. , Gauvin Timothy J. , Heimsath Ernest G. , Higgs Henry N.
Published: September 2010

Actin‐dependent finger‐like protrusions such as filopodia and microvilli are widespread in eukaryotes, but their assembly mechanisms are poorly understood. Filopodia assembly requires at least three biochemical activities on actin: actin filament nucleation, prolonged actin filament elongation, and actin filament bundling. These activities are shared by several mammalian formin proteins, including mDia2, FRL1 (also called FMNL1), and FRL2 (FMNL3). In this paper, we compare the abilities of constructs from these three formins to induce filopodia. FH1‐FH2 constructs of both FRL2 and mDia2 stimulate potent filopodia assembly in multiple cell types, and enrich strongly at filopodia tips. In contrast, FRL1 FH1‐FH2 lacks this activity, despite possessing similar biochemical activities and being highly homologous to FRL2. Chimeric FH1‐FH2 experiments between FRL1 and FRL2 show that, while both an FH1 and an FH2 are needed, either FH1 domain supports filopodia assembly but only FRL2's FH2 domain allows this activity. A mutation that compromises FRL2's barbed end binding ability abolishes filopodia assembly. FRL2's ability to stimulate filopodia assembly is not altered by additional domains (GBD, DID, DAD), but is significantly reduced in the full‐length construct, suggesting that FRL2 is subject to inhibitory regulation. The data suggest that the FH2 domain of FRL2 possesses properties not shared by FRL1 that allow it to generate filopodia. © 2010 Wiley‐Liss, Inc.
Expression of kinesin superfamily genes in cultured hippocampal neurons
Authors: Silverman M. A. , Kaech S. , Ramser E. M. , Lu X. , Lasarev M. R. , Nagalla S. , Banker G.
Published: September 2010

The nature of the different kinesin family members that function in a single, specific neuron type has not been systematically investigated. Here, we used quantitative real‐time PCR to analyze the developmental expression patterns of kinesin family genes in cultured mouse hippocampal neurons, a highly homogeneous population of nerve cells. For purposes of comparison, we also determined the set of kinesins expressed in embryonic and adult hippocampal tissue. Twenty kinesins are expressed at moderate‐to‐high levels in mature hippocampal cultures. These include 9 plus‐end directed kinesins from the Kinesin‐1, ‐2, and ‐3 families that are known to mediate organelle transport and 6 other members of the Kinesin‐3 and ‐4 families that are candidate organelle motors. Hippocampal cultures express high levels of a Kinesin‐13, which regulates microtubule depolymerization, and moderate‐to‐high levels of Kinesin‐9 and ‐14 family members, whose functions are not understood. Twelve additional kinesins, including 10 known mitotic kinesins, are expressed at moderate levels in embryonic hippocampus but at very low levels in mature cultures and the adult hippocampus. Collectively, our findings suggest that kinesins subserve diverse functions within a single type of neuron. © 2010 Wiley‐Liss, Inc.
A phase 2 study of estramustine, docetaxel, and bevacizumab in men with castrate‐resistant prostate cancer
Authors: Picus Joel , Halabi Susan , Kelly W. Kevin , Vogelzang Nicholas J. , Whang Young E. , Kaplan Ellen B. , Stadler Walter M. , Small Eric J. ,   for Cancer and Leukemia Group B
Published: September 2010

BACKGROUND:

The use of docetaxel prolongs survival for patients with castrate‐resistant prostate cancer (CRPC). Inhibition of vascular endothelial growth factor (VEGF) with bevacizumab may further enhance the antitumor effect of docetaxel and estramustine in patients with CRPC.

METHODS:

This cooperative group trial enrolled men with CRPC. Patients received oral estramustine 280 mg 3 times daily on Days 1 through 5 of every cycle plus 70 mg/m2 docetaxel and 15 mg/kg bevacizumab on Day 2 every 3 weeks. Prostate‐specific antigen (PSA) values were monitored every cycle, and imaging studies were obtained every 3 cycles. The primary endpoint was progression‐free survival (PFS), and the secondary objectives were safety, PSA decline, measurable disease response, and overall survival.

RESULTS:

Seventy‐nine patients were enrolled; and 77 patients received a median of 8 cycles and were evaluable. A 50% PSA decline was observed in 58 patients (75%). Twenty‐three of 39 patients with measurable disease had a partial response (59%). The median PFS was 8 months, and the overall median survival was 24 months. Neutropenia without fever (69%), fatigue (25%), and thrombosis/emboli (9%) were the most common severe toxicities. Twenty‐four of 77 patients were removed from protocol treatment because of disease progression, 35 of 77 patients were removed because of a physician or patient decision, and 15 patients were removed secondary to toxicity.

CONCLUSIONS:

The combination of docetaxel, estramustine, and bevacizumab was tolerable but complicated by toxicity. Although the endpoint of PFS did not meet the desired level, encouraging antitumor activity and overall survival were observed. Further phase 3 evaluation of the role of bevacizumab in CRPC is ongoing. Cancer 2011. © 2010 American Cancer Society.
Sunitinib in metastatic renal cell carcinoma patients with brain metastases
Authors: Gore Martin E. , Hariharan Subramanian , Porta Camillo , Bracarda Sergio , Hawkins Robert , Bjarnason Georg A. , Oudard Stéphane , Lee Se‐Hoon , Carteni Giacomo , Nieto Alejandra , Yuan Jinyu , Szczylik Cezary
Published: September 2010

BACKGROUND:

In a broad patient population with metastatic renal cell carcinoma (RCC), enrolled in an open‐label, expanded access program (EAP), the safety profile of sunitinib was manageable, and efficacy results were encouraging. Here, the authors report results for patients with baseline brain metastases participating in this global EAP.

METHODS:

Previously treated and treatment‐naive metastatic RCC patients ≥18 years received sunitinib 50 mg orally, once daily, on Schedule 4/2. Safety was assessed regularly, tumor measurements done per local practice, and survival data collected where possible. Analyses were done in the modified intention‐to‐treat (ITT) population, consisting of all patients who received ≥1 dose of sunitinib.

RESULTS:

As of December 2007, 4564 patients had enrolled in 52 countries. Of these enrollees, 4371 were included in the modified ITT population, of whom 321 (7%) had baseline brain metastases and had received a median of 3 treatment cycles (range 1‐25). Reasons for their discontinuation included lack of efficacy (32%) and adverse events (8%). The most common grade 3‐4 treatment‐related adverse events were fatigue and asthenia (both 7%), thrombocytopenia (6%), and neutropenia (5%), the incidence of which were comparable to that for the overall EAP population. Of 213 evaluable patients, 26 (12%) had an objective response. Median progression‐free survival and overall survival were 5.6 months (95% CI, 5.2‐6.1) and 9.2 months (95% CI, 7.8‐10.9), respectively.

CONCLUSIONS:

In patients with brain metastases from RCC, the safety profile of sunitinib was comparable to that in the general metastatic RCC population, and sunitinib showed evidence of antitumor activity. Cancer 2011. © 2010 American Cancer Society.
Phase 2 trial of the histone deacetylase inhibitor romidepsin for the treatment of refractory multiple myeloma
Authors: Niesvizky Ruben , Ely Scott , Mark Tomer , Aggarwal Sangeeta , Gabrilove Janice L , Wright John J. , Chen‐Kiang Selina , Sparano Joseph A
Published: September 2010

BACKGROUND:

Epigenetic dysregulation is a hallmark of cancer, including multiple myeloma. Inhibitors of histone deacetylases (HDACs) induce DNA hyperacetylation by inhibiting removal of acetyl groups from amino tails on histone proteins, thereby uncoiling condensed chromatin favoring transcription of silenced genes, including tumor suppressor genes. Romidepsin is an HDAC inhibitor that exhibits antiproliferative and apoptotic effects against multiple myeloma cell lines.

METHODS:

A phase 2 trial was performed of romidepsin in patients with multiple myeloma who were refractory to standard therapy. Treatment was comprised of romidepsin (13 mg/m2) given as a 4‐hour intravenous infusion on Days 1, 8, and 15 every 28 days). Thirteen patients received a median of 2 cycles of therapy (range, 1‐7 cycles).

RESULTS:

Although no patients had an objective response, 4 of 12 patients with secretory myeloma exhibited evidence of M‐protein stabilization, and several other patients experienced improvement in bone pain and resolution of hypercalcemia.

CONCLUSIONS:

The results of the current study demonstrate that romidepsin, as a single agent, is unlikely to be associated with a response rate of ≥30% in patients with refractory myeloma, although there was some clinical evidence suggesting a biological effect associated with therapy. Cancer 2011. Published 2010 by the American Cancer Society.
Incidence and risk factors for lower alimentary tract mucositis after 1529 courses of chemotherapy in a homogenous population of oncology patients
Authors: Krishna Somashekar G. , Zhao Weizhi , Grazziutti Monica L. , Sanathkumar Naveen , Barlogie Bart , Anaissie Elias J.
Published: September 2010

BACKGROUND:

Lower alimentary tract mucositis is a serious complication of chemotherapy. The aim of the study was to determine the incidence, risk factors, and mortality of lower alimentary tract mucositis in a homogeneous population of patients with newly diagnosed myeloma receiving similar antineoplastic therapy and standardized supportive care.

METHODS:

Lower alimentary tract mucositis was evaluated among 303 consecutive patients with myeloma (2004‐2007) enrolled in a clinical trial consisting of induction chemotherapy, tandem melphalan‐based autologous stem cell transplantation (ASCT), and consolidation. Lower alimentary tract mucositis was defined as neutropenia‐associated grade II‐IV enteritis/colitis. Pretreatment risk factors were examined including body surface area (BSA), serum albumin (albumin), and estimated creatinine clearance (CrCl). Multiple logistic regression model was used to compute adjusted odds ratio (OR) and 95% confidence intervals (CI).

RESULTS:

Forty‐seven (15.5%) patients developed lower alimentary tract mucositis during 1529 courses of chemotherapy (including 536 melphalan‐based ASCT). Pre‐enrollment BSA <2 m2 (OR, 2.768; 95% CI, 1.200‐6.381; P = .0169) increased the risk for lower alimentary tract mucositis, whereas higher albumin was protective (OR, 0.698; 95% CI, 0.519‐0.940; P = .0177). Pretransplant variables associated with lower alimentary tract mucositis were BSA <2 m2 (OR, 4.451; 95% CI, 1.459‐13.58, P = .0087) and estimated CrCl <60 mL/min (OR, 3.493; 95% CI, 1.173‐10.40; P = .0246). Higher albumin level conferred protection (OR, 0.500; 95% CI, 0.304‐0.820; P = .0061). No lower alimentary tract mucositis‐related death was observed.

CONCLUSIONS:

Lower alimentary tract mucositis is not uncommon among a homogenous population of oncology patients undergoing sequential courses of chemotherapy including melphalan‐based ASCT but does not contribute to mortality. Lower BSA, renal function, and albumin are associated with increased risk for lower alimentary tract mucositis. Cancer 2011. © 2010 American Cancer Society.
Plasticity of the stress response early in life: Mechanisms and significance
Authors: Korosi Aniko , Baram Tallie Z.
Published: September 2010

The concept that early‐life experience influences the brain long‐term has been extensively studied over the past 50 years, whereas genetic factors determine the sequence and levels of expression of specific neuronal genes, this genetic program can be modified enduringly as a result of experience taking place during critical developmental periods. This programming is of major importance because it appears to govern many behavioral and physiological phenotypes and promote susceptibility or resilience to disease. An established example of the consequences of early‐life experience‐induced programming includes the effects of maternal care, where patterns of augmented care result in decreased neuroendocrine stress responses, improved cognition and resilience to depression in the recipients of this care. Here, we discuss the nature and mechanisms of this programming phenomenon, focusing on work from our lab that was inspired by Seymour Levine and his fundamental contributions to the field. © 2010 Wiley Periodicals, Inc. Dev Psychobiol 52: 661–670, 2010.
Yoga and pilates: Associations with body image and disordered‐eating behaviors in a population‐based sample of young adults
Authors: Neumark‐Sztainer Dianne , Eisenberg Marla E. , Wall Melanie , Loth Katie A.
Published: September 2010

Objective

To examine associations between participating in mind‐body activities (yoga/Pilates) and body dissatisfaction and disordered eating (unhealthy and extreme weight control practices and binge eating) in a population‐based sample of young adults.

Method

The sample included 1,030 young men and 1,257 young women (mean age: 25.3 years, SD = 1.7) who participated in Project EAT‐III (Eating and Activity in Teens and Young Adults).

Results

Among women, disordered eating was prevalent in yoga/Pilates participants and nonparticipants, with no differences between the groups. Men participating in yoga/Pilates were more likely to use extreme weight control behaviors (18.6% vs. 6.8%, p = .006) and binge eating (11.6% vs. 4.2%, p = .023), and marginally more likely to use unhealthy weight control behaviors (49.1% vs. 34.5%; p = .053), than nonparticipants after adjusting for sociodemographics, weight status, and overall physical activity.

Discussion

Findings suggest the importance of helping yoga/Pilates instructors recognize that their students may be at risk for disordered eating. © 2010 by Wiley Periodicals, Inc. Int J Eat Disord 2010
Cover Picture: Eur. J. Immunol. 10/10
Authors: Storim Julian , Bröcker Eva B. , Friedl Peter
Published: September 2010

The cover image of this issue shows a dendritic cell with an engaged T cell during homeostatic contact, as captured by confocal miscroscopy; the staining represents F‐actin (green), the phosphotyrosine signal (blue) and CD3 (red). The image was kindly provided by Storim et al. (pp. 2741–2750) whose study analyzes T‐cell migration and cell–cell signaling in short‐lived homeostatic DC–T‐cell interactions. Storim et al. define a dynamic immunological synapse with three distinct signaling sectors in the contact plane.
Preparation of Mesoporous ZnO/Zn(OH)2 Spheres and Their Replication to High Surface TiO2 Materials
Authors: Hwang Yong‐Kyung , Kwon Tae‐Hwan , Park Sung Soo , Yoon Yeo‐Joo , Won Yong Sun , Huh Seong
Published: September 2010

Crystalline mesoporous ZnO/Zn(OH)2 nanocomposite spheres were prepared by a simple method and subsequently used as a hard template for the preparation of amorphous mesoporous TiO2, which showed a very large surface area, 525 m2 g–1. The hydrolytically unstable nature of the ZnO/Zn(OH)2 spheres made the etching process simple and efficient. ZnxTiyOx+2y material was also obtained from different etching processes. The large‐surface amorphous TiO2 was crystallized above 350 °C, and the surface area decreased to 202 m2 g–1. The crystalline mesoporous TiO2 exhibited a good photocatalytic activity in the decomposition of methyl orange under UV irradiation.
Theoretical Investigations towards the Staudinger Reaction Catalyzed by N‐Heterocyclic Carbene: Mechanism and Stereoselectivity
Authors: Tang Ke , Wang Jinhu , Cheng Xueli , Hou Qianqian , Liu Yongjun
Published: September 2010

N‐Heterocyclic carbenes (NHCs) have experimentally proved to be powerful catalysts for the Staudinger reaction ([2+2] cycloaddition of a ketene with an imine) but without giving a clear catalytic mechanism. According to different experimental results, the “ketene‐first” and the “imine‐first” mechanisms, arguing which reactant should be initially activated by the NHC catalyst, have been proposed. Our theoretical investigation by employing density functional theory (DFT) reveals that the reaction mechanism of the NHC‐catalyzed Staudinger reaction is exclusively the “ketene‐first” mechanism, but the competitive reactions of NHC catalysts with ketenes or imines will lead to different experimental observations. On the basis of this conclusion, we found that the NHC‐catalyzed Staudinger reaction would exhibit different stereoselectivities by appropriate choice of the nitrogen substituent of the imines. Furthermore, these results are supposed to be applicable for other nucleophile‐catalyzed Staudinger reactions.
Asymmetric Synthesis of the C1–C13 Fragment of the Marine Metabolite Bistramide K
Authors: Bauder Claude
Published: September 2010

A synthetic study on the construction of the C1–C13 fragment of bistramide K is described. This unit differs from other members of the bistramide family, which are equipped with a pyran structure at C6–C11. In bistramide K, the linear C1–C13 portion contains three stereogenic centers as well as two supplementary (E)‐olefin positions. The key step in the synthesis was the elaboration of the (E)‐olefin C6–C7 by using a Julia–Kocienski reaction between aldehyde 4 and benzothiazolesulfone 15.
Follicular lymphoma at relapse after rituximab containing regimens: comparison of time to event intervals prior to and after 90Y‐ibritumomab‐tiuxetan
Authors: Cicone Francesco , Russo Eleonora , Carpaneto Andrea , Prior John O. , Delaloye Angelika Bischof , Scopinaro Francesco , Ketterer Nicolas
Published: September 2010

Radioimmunotherapies with Zevalin® (RIT‐Z) showed encouraging results in patients with relapsed/refractory follicular lymphoma (FL), leading frequently to failure‐free intervals longer than those achieved by the last previous therapy. We compared time‐to‐event variables obtained before and after RIT‐Z in patients with relapsed FL, previously exposed to rituximab. All patients with relapsed non‐transformed, non‐refractory, non‐rituximab‐naïve FL who have been treated with RIT‐Z in two different centres in Europe were included. Staging and response were assessed by contrast‐enhanced CT in all patients; PET/CT was performed according to local availability. Event‐free survival (EFS) and time to next treatment (TTNT) following the last previous therapy and after RIT‐Z were compared. Pre‐therapy characteristics were tested in univariate analyses for prediction of outcomes. A description of the patterns of relapse was also provided. Among 70 patients treated, only 16 fulfilled the inclusion criteria. They were treated with a median of 3 prior lines of chemo‐immunotherapies, including a median of 2 rituximab‐containing regimens; 6 patients had undergone myeloablative chemotherapy with autologous stem cell rescue (ASCT). Overall response rates were 10 (62%) CR/CRu, 3 (19%) PR and 3 (19%) PD; response rates were similar in patients with prior ASCT. After RIT‐Z only few patients obtained EFS and TTNT longer than after the last previous therapy. All four patients receiving rituximab maintenance were without progression 12 months after RIT‐Z. Relapses occurred in both previously and newly involved sites; a significant association was found between the number of pathologic sites involved prior to RIT‐Z and subsequent TTNT. Despite the excellent response rate, the duration of response was shorter than the previous one confirming the known trend of relapses to occur earlier after subsequent treatments. Rituximab maintenance after RIT‐Z showed encouraging results in terms of prolonging EFS, warranting further studies. Copyright © 2010 John Wiley & Sons, Ltd.
Influence of neurexin 1 (NRXN1) polymorphisms in clozapine response
Authors: Souza Renan P. , Meltzer Herbert Y. , Lieberman Jeffrey A. , Le Foll Bernard , Kennedy James L.
Published: September 2010

Schizophrenia patients show alterations in the synaptic connectivity. However, it remains unknown whether antipsychotic response may be altered depending on the synaptic connectivity. We tested this association using polymorphisms in the neurexin 1 gene (NRXN1). Large NRXN1 deletions have also been associated with schizophrenia. We genotyped four variants in 140 schizophrenia patients assessed prospectively for clozapine response after 6 months. We observed a trend toward association of clozapine response with the rs12467557 (permuted p = 0.051). These results should be read with caution before independent replication. Copyright © 2010 John Wiley & Sons, Ltd.
Activation of the p38 MAPK/Akt/ERK1/2 signal pathways is required for the protein stabilization of CDC6 and cyclin D1 in low‐dose arsenite‐induced cell proliferation
Authors: Liu Youhong , Hock Janet M. , Sullivan Con , Fang Geying , Cox Allison J. , Davis Kathleen T. , Davis Bruce H. , Li Xiong
Published: September 2010

Arsenic trioxide (ATO) is a first‐line anti‐cancer agent for acute promyelocytic leukemia, and induces apoptosis in other solid cancer cell lines including breast cancer cells. However, as with arsenites found in drinking water and used as raw materials for wood preservatives, insecticides, and herbicides, low doses of ATO can induce carcinogenesis after long‐term exposure. At 24 h after exposure, ATO (0.01–1 µM) significantly increased cell proliferation and promoted cell cycle progression from the G1 to S/G2 phases in the non‐tumorigenic MCF10A breast epithelial cell line. The expression of 14 out of 96 cell‐cycle‐associated genes significantly increased, and seven of these genes including cell division cycle 6 (CDC6) and cyclin D1 (CCND1) were closely related to cell cycle progression from G1 to S phase. Low‐dose ATO steadily increased gene transcript and protein levels of both CDC6 and cyclin D1 in a dose‐ and time‐dependent manner. Low‐dose ATO produced reactive oxygen species (ROS), and activated the p38 MAPK, Akt, and ERK1/2 pathways at different time points within 60 min. Small molecular inhibitors and siRNAs inhibiting the activation of p38 MAPK, Akt, and ERK1/2 decreased the ATO‐increased expression of CDC6 protein. Inhibiting the activation of Akt and ERK1/2, but not p38 MAPK, decreased the ATO‐induced expression of cyclin D1 protein. This study reports for the first time that p38 MAPK/Akt/ERK1/2 activation is required for the protein stabilization of CDC6 in addition to cyclin D1 in ATO‐induced cell proliferation and cell cycle modulation from G1 to S phase. J. Cell. Biochem. 111: 1546–1555, 2010. © 2010 Wiley‐Liss, Inc.
Reproductive histology of Tomeurus gracilis Eigenmann, 1909 (Teleostei: Atherinomorpha: Poeciliidae) with comments on evolution of viviparity in atherinomorph fishes
Authors: Parenti Lynne R. , LoNostro Fabiana L. , Grier Harry J.
Published: September 2010

Tomeurus gracilis is a species long considered pivotal in understanding the evolution of livebearing in atherinomorph fishes. Tomeurus gracilis is a zygoparous or embryoparous poeciliid: internal fertilization is followed by females laying fertilized eggs singly or retaining fertilized eggs until or near hatching. Tomeurus was hypothesized as the sister group of the viviparous poeciliids until it was proposed as a close relative of a derived viviparous poeciliid, Cnesterodon, hence nested among viviparous taxa rather than near the root of the tree. Here, we describe and compare reproductive morphological characters of the little‐known Tomeurus with those of representative atherinomorphs. In Tomeurus and Cnesterodon, sperm are packaged in naked sperm bundles, or spermatozeugmata, in a configuration considered here diagnostic of viviparous poeciliids. Testes are single and free sperm are stored in the ovary in both taxa in contrast to oviparous atherinomorphs in which testes are paired and sperm are not packaged and not stored in the ovary. Efferent ducts in Cnesterodon testes and other viviparous poeciliids have a PAS‐positive secretion demonstrating presence of a glycoprotein that inactivates sperm or prevents final sperm maturation. No PAS‐positive staining secretion was observed in Tomeurus or oviparous atherinomorphs. Tomeurus shares apomorphic reproductive characters, such as sperm bundle and testis morphology and a gonopodium, with viviparous poeciliids and plesiomorphic characters, such as a thick zona pellucida with filaments, with oviparous taxa. We do not postulate loss or reversal of viviparity in Tomeurus, and we corroborate its phylogenetic position as sister to the viviparous poeciliids. J. Morphol., 2010. © 2010 Wiley‐Liss, Inc.