bluuebunny/crossref_metadata_2025_split huggingface dataset:
Delayed embryonic development and impaired cell growth and survival in Actg1 null mice
Authors: Bunnell Tina M. , Ervasti James M. 
Published: July 2010

AbstractActins are among the most highly expressed proteins in eukaryotes and play a central role in nearly all aspects of cell biology. While the intricate process of development undoubtedly requires a properly regulated actin cytoskeleton, little is known about the contributions of different actin isoforms during embryogenesis. Of the six actin isoforms, only the two cytoplasmic actins, βcyto‐ and γcyto‐actin, are ubiquitously expressed. We found that γcyto‐actin null (Actg1−/−) mice were fully viable during embryonic development, but most died within 48 h of birth due to respiratory failure and cannibalization by the parents. While no morphogenetic defects were identified, Actg1−/− mice exhibited stunted growth during embryonic and postnatal development as well as delayed cardiac outflow tract formation that resolved by birth. Using primary mouse embryonic fibroblasts, we confirm that γcyto‐actin is not required for cell migration. The Actg1−/− cells, however, exhibited growth impairment and reduced cell viability, defects which perhaps contribute to the stunted growth and developmental delays observed in Actg1−/− embryos. Since the total amount of actin protein was maintained in Actg1−/− cells, our data suggests a distinct requirement for γcyto‐actin in cell growth and survival. © 2010 Wiley‐Liss, Inc.
Perspective on updated treatment guidelines for patients with gastrointestinal stromal tumors
Authors: Blay Jean‐Yves , von Mehren Margaret , Blackstein Martin E. 
Published: July 2010

AbstractGastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract and present predominantly in middle‐aged and older individuals. Historically, the outlook for patients with GISTs was very poor because of the general lack of efficacy of conventional chemotherapy and the often limited surgical options. However, the recognition of the role of mutations of the v‐kit Hardy/Zuckerman 4 feline sarcoma viral oncogene homolog KIT and the platelet derived growth factor receptor alpha gene PDGFRα in the development of GISTs led to the evaluation of potential antitumor effects of the tyrosine kinase inhibitors imatinib and, more recently, sunitinib. Consequently, these molecularly targeted therapies were introduced into clinical practice, and the outcome for patients with GISTs improved considerably. In the last few years, the European Society of Medical Oncology, the National Comprehensive Cancer Network, and the Canadian Advisory Committee on GIST each published a major set of guidelines or practice recommendations for the management of patients with GIST. In the current review, the latest recommendations from each organization are summarized in terms of diagnosis and risk assessment, tumor staging, surgical and/or drug treatment of primary resectable and recurrent metastatic disease, and patient follow‐up and assessment. In addition, areas of consensus and points of divergence among the guidelines are highlighted along with any unresolved issues. Cancer 2010. © 2010 American Cancer Society
Quantitative HER2 protein levels predict outcome in fluorescence in situ hybridization‐positive patients with metastatic breast cancer treated with trastuzumab
Authors: Lipton Allan , Köstler Wolfgang J. , Leitzel Kim , Ali Suhail M. , Sperinde Jeff , Weidler Jodi , Paquet Agnes , Sherwood Thomas , Huang Weidong , Bates Michael ,   the Trastuzumab Response Biomarker Group
Published: July 2010

AbstractBACKGROUND:Only a portion of breast cancer patients currently selected for trastuzumab therapy respond.METHODS:Using a novel assay (HERmark) to quantify total human epidermal growth factor receptor 2 (HER2) expression, the authors examined outcomes in 102 trastuzumab‐treated metastatic breast cancer patients previously assessed as immunohistochemistry (IHC) 3+ by local but not central IHC, or fluorescence in situ hybridization (FISH) positive, and then retested by central FISH.RESULTS:Of 102 MBC patients previously scored as IHC 3+ or 2+/FISH‐positive and treated with trastuzumab‐containing regimens, 98 had both central FISH and HER2 total expression values. Sixty‐six of 76 central FISH‐positive patients (87%) had high HER2 total expression levels (concordant positive), and 19 of 22 central FISH‐negative patients (86%) were HER2 total expression low (concordant negative). Fourteen percent (3 of 22) of central FISH‐negative patients were HER2 total expression high (discordant HER2 total expression high), and 13% (10 of 76) of central FISH‐positive patients were HER2 total expression low (discordant HER2 total expression low). The concordant positive group had a significantly longer time to progression (TTP, median = 11.3 months) compared with the concordant negative group (median TTP, 4.5 months; hazard ratio [HR] = 0.42, P < .001), and also compared with the discordant HER2 total expression low group (median TTP, 3.7 months; HR = 0.43, P = .01). The discordant HER2 total expression low group behaved similarly compared with concordant negatives (HR = 1, P = .99). In analyses restricted to central FISH‐positive patients only (n = 77), Cox proportional hazards multivariate regression identified HER2 total expression as an independent predictor of TTP (HR = 0.29, P = .0015) and overall survival (HR = 0.19, P < .001).CONCLUSIONS:A subset of patients with HER2 gene amplification by FISH express low levels of HER2 protein and have reduced response to trastuzumab‐containing therapy, similar to FISH‐negative patients. This cohort represents a training dataset, and the observed relationships and derived cutoffs require validation in an independent cohort of trastuzumab‐treated metastatic breast cancer patients. Cancer 2010. © 2010 American Cancer Society.
Asymmetric distribution of cadherin 23 and protocadherin 15 in the kinocilial links of avian sensory hair cells
Authors: Goodyear Richard J. , Forge Andy , Legan P. Kevin , Richardson Guy P. 
Published: July 2010

AbstractCadherin 23 and protocadherin 15 are components of tip links, fine filaments that interlink the stereocilia of hair cells and are believed to gate the hair cell's mechanotransducer channels. Tip links are aligned along the hair bundle's axis of mechanosensitivity, stretching obliquely from the top of one stereocilium to the side of an adjacent, taller stereocilium. In guinea pig auditory hair cells, tip links are polarized with cadherin 23 at the upper end and protocadherin 15 at the lower end, where the transducer channel is located. Double immunogold labeling of avian hair cells was used to study the distribution of these two proteins in kinocilial links, a link type that attaches the tallest stereocilia of the hair bundle to the kinocilium. In the kinocilial links of vestibular hair bundles, cadherin 23 localizes to the stereocilium and protocadherin 15 to the kinocilium. The two cadherins are therefore asymmetrically distributed within the kinocilial links but of a polarity that is, within those links that are aligned along the hair bundle's axis of sensitivity, reversed relative to that of tip links. Conventional transmission electron microscopy of hair bundles fixed in the presence of tannic acid reveals a distinct density in the 120–130 nm long kinocilial links that is located 35–40 nm from the kinociliary membrane. The location of this density is consistent with it being the site at which interactions occur in an in trans configuration between the opposing N‐termini of homodimeric forms of cadherin 23 and protocadherin 15. J. Comp. Neurol. 518:4288–4297, 2010. © 2010 Wiley‐Liss, Inc.
Topographic arrangement of the rotundo‐entopallial projection in the pigeon (Columba livia)
Authors: Fredes Felipe , Tapia Sebastian , Letelier Juan Carlos , Marín Gonzalo , Mpodozis Jorge 
Published: July 2010

AbstractThe tectofugal pathway (retina – optic tectum – nucleus rotundus – entopallium) is a prominent route mediating visual discrimination in diurnal birds. Several lines of evidence have shown that at the tecto‐rotundal stage this pathway is composed of multiple parallel channels. Anatomical studies show that the nucleus rotundus is composed of at least four subdivisions, according to differences in cytoarchitectonic, histochemical, and hodological properties. Each of these subdivisions is in receipt of a highly convergent, nontopographic tectal projection, originating from a distinct subset of tecto‐rotundal neurons. Physiological studies show that neurons of different subdivisions respond specifically to different visual dimensions, such as color, luminance, two‐dimensional motion, and in‐depth motion. At present it is less clear whether or to what extent this channel segregation is preserved at the telencephalic stage of the tectofugal pathway. The entopallium shows no obvious subdivisions or laminations. Nevertheless, tract‐tracing experiments show that separate portions of the entopallium receive efferent projections from different rotundal subdivisions, in a way that maintains the rostrocaudal order of these subdivisions. In the present study we investigate in detail the topography of the rotundo‐entopallial projection by means of anterograde and retrograde neuronal tracers. Our results confirm the zonal topography proposed by previous studies and indicate that each zone in the entopallium receives a direct and topographically organized projection from its corresponding rotundal subdivision. These results suggest that the spatial arrangement of the different rotundal functional modules is preserved at the entopallial level. J. Comp. Neurol. 518:4342–4361, 2010. © 2010 Wiley‐Liss, Inc.
Comparative studies of diurnal and nocturnal rodents: Differences in lifestyle result in alterations in cortical field size and number
Authors: Campi Katharine L. , Krubitzer Leah 
Published: July 2010

AbstractIn this study we examine and describe the neuroanatomical organization of sensory cortex in four rodents: laboratory Norway rats (Long Evans; Rattus norvegicus), wild‐caught Norway rats (Rattus norvegicus), wild‐caught California ground squirrels (Spermophilus beecheyi), and wild‐caught Eastern gray squirrels (Sciurus carolinensis). Specifically, we examined the myeloarchitecture and cytochrome oxidase reactivity for several well‐identified areas in visual cortex (areas 17, 18, and 19), somatosensory cortex (areas S1, S2 and PV), and auditory cortex [areas A1 + AAF (R) and TA] and compared the percentage of dorsolateral cortex devoted to each of these areas. Our results demonstrate that squirrels have a larger mean percentage of dorsolateral cortex devoted to visual areas than rats. The difference is due to the greater percentage of cortex devoted to known areas such as area 17 and area 18 and not simply to a difference in the number of visual areas, which ultimately makes this distinction even more pronounced. Furthermore, both rat groups have a larger percentage of the dorsolateral cortex devoted to somatosensory and auditory cortical areas. Differences within groups were also observed. The arboreal squirrel had a larger mean percentage of dorsolateral cortex devoted to areas 17 and 18 compared with the terrestrial squirrel. The laboratory Norway rat had a larger percentage of dorsolateral cortex devoted to both somatosensory and auditory areas than the wild‐caught Norway rat. Our results indicate that differences in sensory apparatus, use of sensory systems, and niche are reflected in the organization and size of cortical areas. J. Comp. Neurol. 518:4491–4512, 2010. © 2010 Wiley‐Liss, Inc.
BMP2 expression in the adult rat brain
Authors: Sato Tomonori , Mikawa Sumiko , Sato Kohji 
Published: July 2010

AbstractBone morphogenetic protein‐2 (BMP2) is a member of the transforming growth factor‐β (TGF‐β) superfamily and plays important roles in multiple biological events. Although BMP2 expression has been well described in the early development of the central nervous system (CNS), little information is available on its expression in the adult CNS. We thus investigated BMP2 expression in the adult rat CNS by using immunohistochemistry. Here we show that BMP2 is widely expressed throughout the adult CNS. In addition, besides intense BMP2 expression in almost all neurons, we found BMP2 expression in astrocytes and ependymal cells. Interestingly, we found that the axons of olfactory sensory neurons express BMP2. In addition, in the glomerular layer, BMP2 was very strongly expressed in some glomeruli, whereas the other glomeruli were weakly stained, suggesting that the variations in BMP2 expression level in each glomerus might be cues for each axon to find its adequate target and to keep its identity. Furthermore, we compared the expression patterns of BMP2 and BMP4. Interestingly, BMP4 was preferentially expressed in the dendrites of several neurons, whereas BMP2 was basically not expressed in the dendrites; however, it was detected in the axons. This means that in a single neuron the localizations of BMP2 and BMP4 are differentially regulated. These data indicate that BMP2 is more widely expressed throughout the adult CNS than previously reported, and its continued abundant expression in the adult brain strongly supports the idea that BMP2 also plays pivotal roles in the adult brain. J. Comp. Neurol. 518:4513–4530, 2010. © 2010 Wiley‐Liss, Inc.
Ovarian hormone‐induced reorganization of oxytocin‐labeled dendrites and synapses lateral to the hypothalamic ventromedial nucleus in female rats
Authors: Griffin Gerald D. , Ferri‐Kolwicz Sarah L. , Reyes Beverly A.S. , Van Bockstaele Elisabeth J. , Flanagan‐Cato Loretta M. 
Published: July 2010

AbstractCentral oxytocin (OT) modulates many social behaviors, including female rat sexual receptivity, quantified as the copulatory stance known as lordosis. The expression of the lordosis response is modulated by OT action in the ventromedial nucleus of the hypothalamus (VMH), as demonstrated by behavioral pharmacology experiments. However, the subcellular localization of OT in this brain region has been unclear. We tested the hypothesis that ovarian hormones reorganize OT‐labeled pre‐ or postsynaptic elements in the fiber complex lateral to the VMH by using immunoelectron microscopy. OT immunolabeling occurred in axonal boutons identified by the presence of small, clear synaptic vesicles and double labeling with the presynaptic markers synaptophysin and vesicular glutamate transporter 2. OT immunoreactivity also was observed in dendritic profiles, verified with double labeling for the dendrite‐specific marker microtubule‐associated protein 2. Ovarian hormones did not alter the density of axonal boutons; however, estradiol treatment reduced the density of dendritic profiles by 34%. This effect was reversed when progesterone was given subsequent to estradiol. The effect of estradiol treatment was specific to dendrites that lacked OT immunostaining; the density of OT‐labeled dendritic profiles remained constant during estradiol treatment. With the estradiol‐induced exit of non‐OT‐labeled dendritic profiles, the remaining OT‐labeled dendritic profiles experienced an increase in their number of synaptic contacts. Thus, hormone treatments that mimic the 4‐day rat estrous cycle provoke a chemically coded reorganization of dendrite innervation in the fiber plexus lateral to the VMH that may underlie the hormone‐specific effect of OT on reproductive behavior. J. Comp. Neurol. 518:4531–4545, 2010. © 2010 Wiley‐Liss, Inc.
Cellobiose Dehydrogenase: A Versatile Catalyst for Electrochemical Applications
Authors: Ludwig Roland , Harreither Wolfgang , Tasca Federico , Gorton Lo 
Published: July 2010

AbstractCellobiose dehydrogenase catalyses the oxidation of aldoses—a simple reaction, a boring enzyme? No, neither for the envisaged bioelectrochemical applications nor mechanistically. The catalytic cycle of this flavocytochrome is complex and modulated by its flexible cytochrome domain, which acts as a built‐in redox mediator. This intramolecular electron transfer is modulated by the pH, an adaptation to the environmental conditions encountered or created by the enzyme‐producing fungi. The cytochrome domain forms the base from which electrons can jump to large terminal electron acceptors, such as redox proteins, and also enables by that path direct electron transfer from the catalytically active flavodehydrogenase domain to electrode surfaces. The application of electrochemical techniques to the elucidation of the molecular and catalytic properties of cellobiose dehydrogenase is discussed and compared to biochemical methods. The results lead to valuable insights into the function of this cellulose‐bound enzyme, but also form the basis of exciting applications in biosensors, biofuel cells and bioelectrocatalysis.
Directional Study of the Optical Properties of Tb3+‐ and Eu3+‐Doped Nanoparticles Embedded in Silica Photonic Crystals
Authors: Bovero Enrico , Yano Kazuhisa , Nakamura Tadashi , Yamada Yuri , van Veggel Frank C. J. M. 
Published: July 2010

AbstractThe effects of the stop band (SB) in colloidal photonic crystals composed of silica spheres containing Eu3+‐ and Tb3+‐doped yttria nanoparticles are analysed. Reflection and transmission spectra indicate movement of the stop band, due to the 111 series of planes, towards shorter wavelengths with increasing angle of observation. The profile of the emission spectra is modified by the presence of the SB depending on the angle of measurement. Such a modification is more effective for a narrow emission band and it is thus more evident in the case of Tb3+ than Eu3+. An angular effect is also observed in the lifetime, which presents two maxima and one minimum. In the case of Tb3+ the maxima are at observation angles of 35 and 50°, and the minimum at 45°. We attribute this behaviour to penetration of the excitation beam at 475 nm modulated by the stop band. The ions excited in this way emit from different depths in the crystal, and therefore their lifetime will be affected differently by the same stop band, depending on the thickness of the crystal that must be crossed. Eu3+ shows a similar but less pronounced effect for two reasons: first, the main stop band (due to the 111 planes) is not effective at the excitation wavelength of 392 nm; second, the broadness of the Eu3+ emission is comparable to the width of the SB, and a decrease in the transition rate at the wavelength of the SB maximum is compensated by an increase at the sides of the SB.
Detection of molecular targets on the surface of CD34+CD38− bone marrow cells in myelodysplastic syndromes
Authors: Xie Wei , Wang Xuhua , Du Wen , Liu Wei , Qin Xiaoming , Huang Shiang 
Published: July 2010

AbstractMyelodysplastic syndrome (MDS) is a kind of clonal stem‐cell disorder in which aberration within a hematopoietic stem cell (HSC) gives rise to the entire disease as in acute myeloid leukemia (AML). Studies have showed that contrasting normal stem cells, AML stem cells express CD96 and CD123, but lack of CD90, although both of them reside within the CD34+CD38− population. So far, little is known about expression of the markers on MDS HSC. In this study, we analyzed the immunophenotypic characteristics of CD34+CD38− bone marrow (BM) cells by multicolor flow cytometry in 38 patients with MDS and 10 control patients. We found that CD34+CD38− BM cells coexpressed CD13, CD33, CD117, CD133, and HLA‐DR almost in all patients, but in MDS they expressed higher amounts of CD13 (79% ± 16% vs. 36% ± 13%, P < 0.05) and CD133 (66% ± 20% vs. 25% ± 13%, P < 0.05). CD90 was expressed in all control patients but just in 63% of patients with MDS. No control patients had an expression of CD2, CD5, CD7, CD44, CD96, and CD123, which expressed variable amounts in 17–53% of patients with MDS. The level of CD13 in RCMD (89% ± 7%), RAEB‐1 (88% ± 11%), and RAEB‐2 (81% ± 13%) were obviously higher than that of RA (63% ± 16%, P < 0.05). CD2, CD5, and CD7 were more frequently observed in RAEB or INT and HIGH‐R cases. Taken together, we demonstrate MDS stem cells display deranged phenotypic abnormalities that may make them particularly difficult to eradicate using therapies targeted against surface antigens, and the percentage of cells expressing CD13 is notably higher in patients with high‐grade MDS that may be a potential prognostic indicator of MDS in the future. © 2010 International Society for Advancement of Cytometry
Digital analysis and sorting of fluorescence lifetime by flow cytometry
Authors: Houston Jessica P. , Naivar Mark A. , Freyer James P. 
Published: July 2010

AbstractFrequency‐domain flow cytometry techniques are combined with modifications to the digital signal‐processing capabilities of the open reconfigurable cytometric acquisition system (ORCAS) to analyze fluorescence decay lifetimes and control sorting. Real‐time fluorescence lifetime analysis is accomplished by rapidly digitizing correlated, radiofrequency (RF)‐modulated detector signals, implementing Fourier analysis programming with ORCAS' digital signal processor (DSP) and converting the processed data into standard cytometric list mode data. To systematically test the capabilities of the ORCAS 50 MS/sec analog‐to‐digital converter (ADC) and our DSP programming, an error analysis was performed using simulated light scatter and fluorescence waveforms (0.5–25 ns simulated lifetime), pulse widths ranging from 2 to 15 μs, and modulation frequencies from 2.5 to 16.667 MHz. The standard deviations of digitally acquired lifetime values ranged from 0.112 to >2 ns, corresponding to errors in actual phase shifts from 0.0142° to 1.6°. The lowest coefficients of variation (<1%) were found for 10‐MHz modulated waveforms having pulse widths of 6 μs and simulated lifetimes of 4 ns. Direct comparison of the digital analysis system to a previous analog phase‐sensitive flow cytometer demonstrated similar precision and accuracy on measurements of a range of fluorescent microspheres, unstained cells, and cells stained with three common fluorophores. Sorting based on fluorescence lifetime was accomplished by adding analog outputs to ORCAS and interfacing with a commercial cell sorter with a RF‐modulated solid‐state laser. Two populations of fluorescent microspheres with overlapping fluorescence intensities but different lifetimes (2 and 7 ns) were separated to ∼98% purity. Overall, the digital signal acquisition and processing methods we introduce present a simple yet robust approach to phase‐sensitive measurements in flow cytometry. The ability to simply and inexpensively implement this system on a commercial flow sorter will allow both better dissemination of this technology and better exploitation of the traditionally underutilized parameter of fluorescence lifetime. Published 2010 Wiley‐Liss, Inc.
IL‐10 produced by activated human B cells regulates CD4+ T‐cell activation in vitro
Authors: Bouaziz Jean‐David , Calbo Sebastien , Maho‐Vaillant Maud , Saussine Anne , Bagot Martine , Bensussan Armand , Musette Philippe 
Published: July 2010

AbstractIL‐10‐producing regulatory B cells have been identified in mice and shown to downregulate inflammation, making them potentially important for maintenance of tolerance. In this study, we isolated B cells from human blood and spleen, and showed that after a short period of ex vivo stimulation a number of these cells produced IL‐10. The IL‐10‐producing B cells did not fall within a single clearly defined subpopulation, but were enriched in both the memory (CD27+) and the transitional (CD38high) B‐cell compartments. Combined CpG‐B+anti‐Ig stimulation was the most potent IL‐10 stimulus tested. B cells stimulated in this way inhibited CD4+CD25− T‐cell proliferation in vitro by a partially IL‐10‐dependent mechanism. These findings imply that manipulating IL‐10 production by human B cells could be a useful therapeutic strategy for modulating immune responses in humans.