bluuebunny/crossref_metadata_2025_split huggingface dataset:
Changes in Notch signaling coordinates maintenance and differentiation of the Drosophila larval optic lobe neuroepithelia
Authors: Weng Mo , Haenfler Jill M. , Lee Cheng‐Yu 
Published: October 2011

AbstractA dynamic balance between stem cell maintenance and differentiation paces generation of post‐mitotic progeny during normal development and maintenance of homeostasis. Recent studies show that Notch plays a key role in regulating the identity of neuroepithelial stem cells, which generate terminally differentiated neurons that populate the adult optic lobe via the intermediate progenitor cell type called neuroblast. Thus, understanding how Notch controls neuroepithelial cell maintenance and neuroblast formation will provide critical insight into the intricate regulation of stem cell function during tissue morphogenesis. Here, we showed that a low level of Notch signaling functions to maintain the neuroepithelial cell identity by suppressing the expression of pointedP1 gene through the transcriptional repressor Anterior open. Increased Notch signaling, which coincides with transient cell cycle arrest but precedes the expression of PointedP1 in cells near the medial edge of neuroepithelia, defines transitioning neuroepithelial cells that are in the process of acquiring the neuroblast identity. Transient up‐regulation of Notch signaling in transitioning neuroepithelial cells decreases their sensitivity to PointedP1 and prevents them from becoming converted into neuroblasts prematurely. Down‐regulation of Notch signaling combined with a high level of PointedP1 trigger a synchronous conversion from transitioning neuroepithelial cells to immature neuroblasts at the medial edge of neuroepithelia. Thus, changes in Notch signaling orchestrate a dynamic balance between maintenance and conversion of neuroepithelial cells during optic lobe neurogenesis. © 2011 Wiley Periodicals, Inc. Develop Neurobiol, 2012
Deficiency in crumbs homolog 2 (Crb2) affects gastrulation and results in embryonic lethality in mice
Authors: Xiao Zhijie , Patrakka Jaakko , Nukui Masatoshi , Chi Lijun , Niu Dadi , Betsholtz Christer , Pikkarainen Timo , Vainio Seppo , Tryggvason Karl 
Published: October 2011

AbstractThe Crumbs family of transmembrane proteins has an important role in the differentiation of the apical membrane domain in various cell types, regulating such processes as epithelial cell polarization. The mammalian Crumbs protein family is composed of three members. Here, we inactivated the mouse Crb2 gene with gene‐targeting techniques and found that the protein is crucial for early embryonic development with severe abnormalities appearing in Crb2‐deficient embryos at late‐gastrulation. Our findings indicate that the primary defect in the mutant embryos is disturbed polarity of the epiblast cells at the primitive streak, which affects epithelial to mesenchymal transition (EMT) during gastrulation, resulting in impaired mesoderm and endoderm formation, and embryonic lethality by embryonic day 12.5. These findings therefore indicate a novel role for the Crumbs family of proteins. Developmental Dynamics 240:2646–2656, 2011. © 2011 Wiley Periodicals, Inc.
Hyperactive BMP signaling induced by ALK2R206Hrequires type II receptor function in aDrosophilamodel for classic fibrodysplasia ossificans progressiva
Authors: Le Viet Q. , Wharton Kristi A. 
Published: October 2011

AbstractBackground:Fibrodysplasia Ossificans Progressiva (FOP) is an autosomal dominant disorder characterized by episodic deposition of heterotopic bone in place of soft connective tissue. All FOP‐associated mutations map to the BMP type I receptor, ALK2, with the ALK2R206Hmutant form found in the vast majority of patients. The mechanism(s) regulating the expressivity of hyperactive ALK2R206Hsignaling throughout a patient's life is not well understood.Results:InDrosophila, human ALK2R206Hreceptor induces hyperactive BMP signaling. As in vertebrates, elevated signaling associated with ALK2R206HinDrosophilais ligand‐independent. We found that a key determinant for ALK2R206Hhyperactivity is a functional type II receptor. Furthermore, our results indicate that like itsDrosophilaortholog, Saxophone (Sax), wild‐type ALK2 can antagonize, as well as promote, BMP signaling.Conclusions:The dual function of ALK2 is of particular interest given the heterozygous nature of FOP, as the normal interplay between such disparate behaviors could be shifted by the presence of ALK2R206Hreceptors. Our studies provide a compelling example forDrosophilaas a model organism to study the molecular underpinnings of complex human syndromes such as FOP. Developmental Dynamics 241:200–214, 2012. © 2011 Wiley Periodicals, Inc.
Oxidation versus Dioxygenation of Catechol: The Iron–Bispidine System
Authors: Comba Peter , Wadepohl Hubert , Wunderlich Steffen 
Published: October 2011

AbstractThe iron–bispidine‐catalyzed oxidation and dioxygenation (catechol dioxygenase activity) [i.e., the oxidation of 3,5‐di‐tert‐butylcatecholate (dbc2–) by [FeII(L)X2]n+ (L = 3,7‐dimethyl‐9‐oxo‐2,4‐bis(2‐pyridyl)‐3,7‐diazabicyclo[3.3.1]nonane‐1,5‐dicarboxylate methyl ester)] and air (O2) was studied experimentally and supported by the analysis of the X‐ray crystal structure of [Fe(L·MeOH)(tcc)][B(Ph)4] with the deactivated tetrachlorocatecholate tcc2– and a DFT‐based analysis. The [FeII(L)X2]n+/O2/dbc2– system catalyzes the intradiol cleavage of dbc2– but with a relatively low activity (5 % yield); most of the substrate is oxidized in a two‐electron oxidation to the benzoquinone (dbq) product (48 % yield). The crystallographic and DFT‐based theoretical analyses indicate that this is due to the high oxidation potential of the FeIII oxidant (fast and efficient electron transfer), that is, the oxidation to the benzoquinone side product is faster, and due to the bonding mode of the catecholate substrate to the FeIII oxidant, with little spin density transferred to the catecholate substrate.
Convergent Preparation of DimLex Hexasaccharide Analogues
Authors: Hendel Jenifer L. , Auzanneau France‐Isabelle 
Published: October 2011

AbstractWe report the convergent preparation of four hexasaccharides to be used towards the synthesis of a safe anticancer vaccine based on the tumor‐associated carbohydrate antigen dimLex. A common trisaccharide intermediate was first synthesized as a precursor to the tetrasaccharide backbones. These tetrasaccharides were then converted into diol acceptors and fucosylated at O‐3 of both glucosamine residues. The conditions required to promote fucosylation at O‐3 of the reducing end glucosamine units led to some loss of the fucosyl units already introduced at O‐3 of the nonreducing end glucosamine residues. Despite this hurdle, optimization of the glycosylation conditions provided the desired hexasaccharides in sufficient quantities to prepare the final analogues. Propyl glycosides and cysteamine adducts were prepared easily in two steps from the protected allyl glycoside hexasaccharides, and a one‐step deprotection under metal‐dissolving conditions was key to our deprotection strategy.
Microfluidic devices with disposable enzyme electrode for electrochemical monitoring of glucose concentrations
Authors: Li Xin , Zhang Fan , Shi Jian , Wang Li , Tian Jing‐Hua , Zhou Xiong‐Tu , Jiang Lian‐Mei , Liu Li , Zhao Zhen‐Jie , He Pin‐Gang , Chen Yong 
Published: October 2011

AbstractThis article describes the fabrication of tube‐like microchannels made of UV curable polymer on a glass substrate and the device assembling with a disposable enzyme‐working electrode for high‐sensitivity electrochemical detection. While both reference and counter electrodes are patterned on the surface of the glass substrate, the working electrode is flipped on the top of the channel with an open access, providing a face‐to‐face probing configuration. When the enzyme electrode is contaminated or degraded, it can be easily replaced by a new one, keeping the main body of the device and the detection schema unchanged. Using glucose oxidase‐coated gold electrodes, we were able to determine a linear amperometry response to the glucose concentrations in the range of 2–16 mM. By replacing the as‐prepared working electrode by the one after thermal treatments, we showed a much more degraded enzyme electrode activity, enabling efficient determination of the electrode quality as well as the whole process optimization.
Integration of microchip electrophoresis with electrochemical detection using an epoxy‐based molding method to embed multiple electrode materials
Authors: Johnson Alicia S. , Selimovic Asmira , Martin R. Scott 
Published: October 2011

AbstractThis paper describes the use of epoxy‐encapsulated electrodes to integrate microchip‐based electrophoresis with electrochemical detection. Devices with various electrode combinations can easily be developed. This includes a palladium decoupler with a downstream working electrode material of either gold, mercury/gold, platinum, glassy carbon, or a carbon fiber bundle. Additional device components such as the platinum wires for the electrophoresis separation and the counter electrode for detection can also be integrated into the epoxy base. The effect of the decoupler configuration was studied in terms of the separation performance, detector noise, and the ability to analyze samples of a high ionic strength. The ability of both glassy carbon and carbon fiber bundle electrodes to analyze a complex mixture was demonstrated. It was also shown that a PDMS‐based valving microchip can be used along with the epoxy‐embedded electrodes to integrate microdialysis sampling with microchip electrophoresis and electrochemical detection, with the microdialysis tubing also being embedded in the epoxy substrate. This approach enables one to vary the detection electrode material as desired in a manner where the electrodes can be polished and modified as is done with electrochemical flow cells used in liquid chromatography.
Lysosomal exocytosis in Schwann cells contributes to axon remyelination
Authors: Chen Gang , Zhang Zhijun , Wei Zhongya , Cheng Qiong , Li Xia , Li Wei , Duan Shumin , Gu Xiaosong 
Published: October 2011

AbstractMyelin biogenesis is a complex process involving coordinated exocytosis, endocytosis, mRNA transport, and cytoskeletal dynamics. Although abnormalities of myelin are common in lysosomal storage diseases, our understanding of the role of lysosomes in the formation and maintenance of myelin is still limited. Here, we show that late endosomes/lysosomes in Schwann cells contain abundant myelin protein P0, which accounts for over half the total protein of compact myelin in the peripheral nervous system and exhibit Ca2+‐dependent exocytosis in response to various stimuli. Downregulation of Rab27a, a small GTPase required for the trafficking of the secretory lysosomes to the plasma membrane, largely blocked lysosomal exocytosis in Schwann cells and reduced the remyelination of regenerated sciatic nerve. These findings highlight a novel role for lysosomes in Schwann cells and suggest that the regulated lysosome exocytosis in Schwann cells may have important physiological and pathological significance in the peripheral nervous system. © 2011 Wiley Periodicals, Inc.
Near and far space: Understanding the neural mechanisms of spatial attention
Authors: Lane Alison R. , Ball Keira , Smith Daniel T. , Schenk Thomas , Ellison Amanda 
Published: October 2011

AbstractVisuospatial neglect is a multicomponent syndrome, and one dissociation reported is between neglect for near (peripersonal) and far (extrapersonal) space. Owing to patient heterogeneity and extensive lesions, it is difficult to determine the precise neural mechanisms underlying this dissociation using clinical methodology. In this study, transcranial magnetic stimulation was used to examine the involvement of three areas in the undamaged brain, while participants completed a conjunction search task in near and far space. The brain areas investigated were right posterior parietal cortex (rPPC), right frontal eye field (rFEF), and right ventral occipital cortex (rVO), each of which has been implicated in visuospatial processing. The results revealed a double dissociation, whereby rPPC was involved for search in near space only, whilst rVO only became necessary when the task was completed in far space. These data provide clear evidence for a dorsal and ventral dissociation between the processing of near and far space, which is compatible with the functional roles previously attributed to the two streams. For example, the involvement of the dorsal stream in near space reflects its role in vision for action, because it is within this spatial location that actions can be performed. The results also revealed that rFEF is involved in the processing of visual search in both near and far space and may contribute to visuospatial attention and/or the control of eye‐movements irrespective of spatial frame. We discuss our results with respect to their clear ramifications for clinical diagnosis and neurorehabilitation. Hum Brain Mapp, 2013. © 2011 Wiley Periodicals, Inc.
Human papillomavirus infection in women with and without cervical cancer in Tehran, Iran
Authors: Khodakarami Nahid , Clifford Gary M. , Yavari Parvin , Farzaneh Farah , Salehpour Saghar , Broutet Natalie , Bathija Heli , Heideman Daniëlle A.M. , van Kemenade Folkert J. , Meijer Chris J.L.M. , Hosseini Seyed Jalil , Franceschi Silvia 
Published: October 2011

AbstractNo data exist on the population prevalence of, or risk factors for, human papillomavirus (HPV) infection in Iran or the Middle East. Cervical specimens were obtained from 825 married women aged 18–59 years from the general population of Tehran, Iran and from 45 locally diagnosed invasive cervical cancers (ICC) according to the standardized protocol of the International Agency for Research on Cancer HPV Prevalence Surveys. HPV was detected and genotyped using a GP5+/6+ PCR‐based assay. HPV prevalence in the general population was 7.8% (95% confidence interval: 6.0–9.8) (5.1% of high‐risk types), with no significant variation by age. HPV positivity was significantly higher among divorced women, women in polygamous marriages and those reporting husband's absence from home for >7 nights/month. HPV16/18 accounted for 30 and 82.2% of HPV‐positive women in the general population and ICC, respectively. Cervical cancer prevention policies should take into account the relatively low HPV prevalence in this population.
α‐Tocopheryloxyacetic acid is superior to α‐tocopheryl succinate in suppressing HER2‐high breast carcinomas due to its higher stability
Authors: Dong Lan‐Feng , Grant Gary , Massa Helen , Zobalova Renata , Akporiaye Emmanuel , Neuzil Jiri 
Published: October 2011

AbstractBreast cancer is the number one neoplastic disease of women, with the HER2‐high carcinomas presenting a considerable challenge for efficient treatment. Therefore, a search for novel agents active against this type of cancer is warranted. We tested two vitamin E (VE) analogs, the esterase‐hydrolyzable α‐tocopheryl succinate (α‐TOS) and the non‐hydrolyzable ether α‐tocopheryloxyacetic acid (α‐TEA) for their effects on HER2‐positive breast carcinomas using a breast tumor mouse model and breast cancer cell lines. Ultrasound imaging documented that α‐TEA suppressed breast carcinomas in the transgenic animals more efficiently than found for its ester counterpart. However, both agents exerted a comparable apoptotic effect on the NeuTL breast cancer cells derived from the FVB/N c‐neu mice as well as in the human MBA‐MD‐453 and MCF7HER2‐18 cells with high level of HER2. The superior anti‐tumor effect of α‐TEA over α‐TOS in vivo can be explained by longer persistence of the former in mice, possibly due to the enhanced plasma and hepatic processing of α‐TOS in comparison to the esterase‐non‐cleavable α‐TEA. Indeed, the stability of α‐TOS in plasma was inferior to that of α‐TEA. We propose that α‐TEA is a promising drug efficient against breast cancer, as documented by its effect on experimental HER2‐positive breast carcinomas that present a considerable problem in cancer management.
Survival in patients with human papillomavirus positive tonsillar cancer in relation to treatment
Authors: Attner Per , Näsman Anders , Du Juan , Hammarstedt Lalle , Ramqvist Torbjörn , Lindholm Johan , Munck‐Wikland Eva , Dalianis Tina , Marklund Linda 
Published: October 2011

AbstractThe incidence of tonsillar cancer and the proportion of human papillomavirus (HPV) positive tonsillar cancer cases have increased in the last decades. In parallel, treatment for tonsillar cancer has been intensified e.g., by accelerated radiotherapy, and chemotherapy, resulting in more side effects. Patients with HPV‐positive tonsillar cancer have better prognosis than those with HPV‐negative tumors, and the former group could hypothetically benefit from reduced, less‐toxic treatment without compromising survival. Here, we therefore evaluated possible differences in overall and disease‐specific survival after different oncological treatments in 153 patients with HPV DNA‐ and P16‐positive tonsillar cancer who were diagnosed and treated with intent to cure between 2000 and 2007, in Stockholm, Sweden. Of these patients, 86 were treated with conventional radiotherapy, 40 were treated with accelerated radiotherapy and 27 were treated with chemoradiotherapy. There were no significant differences in overall or disease‐free survival between the groups. However, there was a trend, implying a beneficial effect of the intensified treatment, with chemoradiotherapy being better than radiotherapy despite that more patients had stage IV disease in the former group; and accelerated radiotherapy being better than conventional radiotherapy. This needs to be followed further in larger more homogenous groups of patients. In conclusion, patients with HPV‐positive tonsillar cancer treated with conventional‐ or accelerated radiotherapy or chemoradiotherapy disclosed similar survival rates. The trend for better survival and less metastasis after intensified treatment underlines the need for large prospective studies comparing less intense to more intense treatment (chemoradiotherapy).
Food‐frequency questionnaire‐based estimates of total antioxidant capacity and risk of non‐Hodgkin lymphoma
Authors: Holtan Shernan G. , O'Connor Helen M. , Fredericksen Zachary S. , Liebow Mark , Thompson Carrie A. , Macon William R. , Micallef Ivana N. , Wang Alice H. , Slager Susan L. , Habermann Thomas M. , Call Timothy G. , Cerhan James R. 
Published: October 2011

AbstractAntioxidants, primarily from fruits and vegetables, have been hypothesized to protect against non‐Hodgkin lymphoma (NHL). The oxygen radical absorbance capacity (ORAC) assay, which measures total antioxidant capacity of individual foods and accounts for synergism, can be estimated using a food‐frequency questionnaire (FFQ). We tested the hypothesis that higher intake of antioxidant nutrients from foods, supplements and FFQ‐based ORAC values are associated with a lower risk of NHL in a clinic‐based study of 603 incident cases and 1,007 frequency‐matched controls. Diet was assessed with a 128‐item FFQ. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals adjusted for age, sex, residence and total energy. Dietary intake of α‐tocopherol (OR = 0.50; p‐trend = 0.0002), β‐carotene (OR = 0.58; p‐trend = 0.0005), lutein/zeaxanthin (OR = 0.62; p‐trend = 0.005), zinc (OR = 0.54; p‐trend = 0.003) and chromium (OR = 0.68; p‐trend = 0.032) was inversely associated with NHL risk. Inclusion of supplement use had little impact on these associations. Total vegetables (OR = 0.52; p‐trend < 0.0001), particularly green leafy (OR = 0.52; p‐trend<0.0001) and cruciferous (OR = 0.68; p‐trend = 0.045) vegetables, were inversely associated with NHL risk. NHL risk was inversely associated with both hydrophilic ORAC (OR = 0.61, p‐trend = 0.003) and lipophilic ORAC (OR = 0.48, p‐trend = 0.0002), although after simultaneous adjustment for other antioxidants or total vegetables, only the association for lipophilic ORAC remained significant. There was no striking heterogeneity in results across the common NHL subtypes. Higher antioxidant intake as estimated by the FFQ‐ORAC, particularly the lipophilic component, was associated with a lower NHL risk after accounting for other antioxidant nutrients and vegetable intake, supporting this as potentially useful summary measure of total antioxidant intake.
Tumor TP53 expression status, body mass index and prognosis in colorectal cancer
Authors: Morikawa Teppei , Kuchiba Aya , Liao Xiaoyun , Imamura Yu , Yamauchi Mai , Qian Zhi Rong , Nishihara Reiko , Sato Kaori , Meyerhardt Jeffrey A. , Fuchs Charles S. , Ogino Shuji 
Published: October 2011

AbstractInactivation of the TP53 (p53) pathway by TP53 mutations is one of key steps in colorectal carcinogenesis. TP53 also plays an important role in cellular energy metabolism. We hypothesized that TP53‐altered tumor cells might behave aggressively independent of energy balance, while progression of TP53‐intact cells might depend on excess energy balance. Utilizing a database of 1,060 colon and rectal cancer patients in two prospective cohort studies, we evaluated TP53 expression by immunohistochemistry. Among 1,060 colorectal cancers, 457 (43%) tumors were positive for TP53. Cox proportional hazards model was used to compute mortality hazard ratio (HR), adjusting for clinical and tumoral features, including microsatellite instability, the CpG island methylator phenotype, LINE‐1 methylation, KRAS, BRAF and PIK3CA. TP53 positivity was not significantly associated with cancer‐specific survival in univariate analysis with HR of 1.16 [95% confidence interval (CI) = 0.92–1.45], which became significant after stage adjustment (multivariate HR = 1.30; 95% CI = 1.02–1.65). Notably, we found a possible modifying effect of patient's body mass index (BMI) on tumor TP53. In non‐obese patients (BMI < 30 kg/m2), TP53 positivity was associated with shorter cancer‐specific survival (multivariate HR = 1.53; 95% CI = 1.17‐2.00), while TP53 positivity was not significantly associated with survival among obese patients (BMI ≥30 kg/m2). Effect of TP53 positivity on cancer‐specific survival significantly differed by BMI (pinteraction = 0.0051). The adverse effect of obesity on patient mortality was limited to TP53‐negative patients. These molecular pathological epidemiology data may support a dual role of TP53 alterations in cell‐cycle deregulation and cell autonomy with respect to energy balance status.
Benzothiophene carboxamide derivatives as novel antimalarials
Authors: Banerjee Tanushree , Kapoor Neha , Surolia Namita , Surolia Avadhesha 
Published: October 2011

AbstractBromo‐benzothiophene carboxamide derivatives have been shown in the preceding article to inhibit Plasmodium falciparum Enoyl‐ACP reductase. Here, we report bromo‐benzothiophene carboxamide derivatives as potent inhibitors of Plasmodium asexual blood‐stages in vitro as well as in vivo in the mouse model. These compounds specifically impair the development of metabolically active trophozoite stage of intraerythrocytic cycle and the intravenous administration of 3‐bromo‐N‐(4‐fluorobenzyl)‐benzo[b]thiophene‐2‐carboxamide (compound 6) enhances the longevity of P. berghei infected mice by 2 weeks compared to disease control animals thereby preventing the onset of ataxia and convulsions in treated mice. These compounds thus hold promise for the development of potent antimalarials. © 2011 IUBMB IUBMB Life, 63(12): 1111–1115, 2011