bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical effect of temozolomide‐based chemotherapy in poorly differentiated endocrine carcinoma after progression on first‐line chemotherapy
Authors: Welin Staffan , Sorbye Halfdan , Sebjornsen Sigrunn , Knappskog Stian , Busch Christian , Öberg Kjell 
Published: March 2011

AbstractBACKGROUND:Patients with metastatic poorly differentiated endocrine carcinoma (PDEC) usually have a short survival. The chemotherapy combination of cisplatin and etoposide is frequently used as first‐line palliative chemotherapy. There are, however, no published studies concerning second‐line treatment of the disease. Temozolomide has shown clinical effect in well‐differentiated endocrine carcinomas. This study was performed to evaluate the effect of temozolomide in PDEC patients who had progressed on first‐line treatment.METHODS:Twenty‐five patients with PDEC (mainly gastrointestinal) were treated with temozolomide alone or in combination with capecitabine. A subset of patient also received bevacizumab. MGMT methylation was analyzed in tissue specimens. Data were collected retrospectively.RESULTS:One patient had a complete response, and 7 patients had partial response (33% response rate). Median duration of response was 19 months. Another 9 (38%) patients had a stable disease, after progression at inclusion, with a median duration of 18 months. Median progression‐free survival for all patients was 6 months, and median overall survival was 22 months. Only 1 patient had a MGMT methylation.CONCLUSIONS:Treatment with temozolomide alone or in combination with capecitabine and bevacizumab resulted in objective response or stabilization in 71% of PDEC patients who failed on first‐line chemotherapy. These results indicated that temozolomide may be used as second‐line treatment in PDEC. Cancer 2011;. © 2011 American Cancer Society.
Differential regulation of the expression of neurotrophin receptors in rat extraocular motoneurons after lesion
Authors: Morcuende Sara , Matarredona Esperanza R. , Benítez‐Temiño Beatriz , Muñoz‐Hernández Rocío , Pastor Ángel M. , de la Cruz Rosa R. 
Published: March 2011

AbstractNeurotrophins acting through high‐affinity tyrosine kinase receptors (trkA, trkB, and trkC) play a crucial role in regulating survival and maintenance of specific neuronal functions after injury. Adult motoneurons supplying extraocular muscles survive after disconnection from the target, but suffer dramatic changes in morphological and physiological properties, due in part to the loss of their trophic support from the muscle. To investigate the dependence of the adult rat extraocular motoneurons on neurotrophins, we examined trkA, trkB, and trkC mRNA expression after axotomy by in situ hybridization. trkA mRNA expression was detectable at low levels in unlesioned motoneurons, and its expression was downregulated 1 and 3 days after injury. Expression of trkB and trkC mRNAs was stronger, and after axotomy a simultaneous, but inverse regulation of both receptors was observed. Thus, whereas a considerable increase in trkB expression was seen about 2 weeks after axotomy, the expression of trkC mRNA had decreased at the same post‐lesion period. Injured extraocular motoneurons also experienced an initial induction in expression of calcitonin gene‐related peptide and a transient downregulation of cholinergic characteristics, indicating a switch in the phenotype from a transmitter‐specific to a regenerative state. These results suggest that specific neurotrophins may contribute differentially to the survival and regenerative responses of extraocular motoneurons after lesion. J. Comp. Neurol. 519:2335–2352, 2011. © 2011 Wiley‐Liss, Inc.
Recovery and aging of serotonergic fibers after single and intermittent MDMA treatment in dark agouti rat
Authors: Ádori Csaba , Andó Rómeó D. , Szekeres Mária , Gutknecht Lise , Kovács Gábor G. , Hunyady László , Lesch Klaus‐Peter , Bagdy György 
Published: March 2011

Abstract3,4‐Methylenedioxymethamphetamine (MDMA; ecstasy) is a popular party drug known to cause selective serotonergic damage. Here we examined the long‐term recovery and aging of serotonergic fibers and levels of brain‐derived neurotrophic factor (BDNF) after intermittent MDMA administration (15 mg kg−1 i.p. every 7th day for 4 weeks, MDMA ×4) and a single‐dose treatment (15 mg kg−1 i.p., MDMA ×1) in adolescent/young adult male Dark Agouti rats. After MDMA treatment, tryptophan hydroxylase‐immunoreactive fiber density decreased and then recovered in all brain regions. Recovery was more pronounced in the MDMA ×4 group compared with the MDMA ×1 group, but similar long‐term BDNF responses were found after both treatments. Twenty‐two months after treatment, there were fewer clusters of aberrant serotonergic fibers in the parietal cortex in the MDMA ×4 group compared with the MDMA ×1 group. There was no difference in the density of microglial cells or astrocytes in treated groups versus the control 22 months after the treatments. These results indicate that recovery of serotonergic fibers is faster after intermittent MDMA treatment than after single‐dose administration, and differences in BDNF levels per se are unlikely to account for this difference. Moreover, it seems that intermittent MDMA treatment attenuates the morphological signs of aging in serotonergic fibers. In addition, neither intermittent nor single‐dose MDMA exposition of young animals induces accelerated aging processes or neurodegeneration in senescence, as indicated by the unaltered densities of microglial cells and astrocytes in the treated groups compared with the control. J. Comp. Neurol. 519:2353–2378, 2011. © 2011 Wiley‐Liss, Inc.
Mapping of endogenous morphine‐like compounds in the adult mouse brain: Evidence of their localization in astrocytes and GABAergic cells
Authors: Laux Alexis , Muller Arnaud H. , Miehe Monique , Dirrig‐Grosch Sylvie , Deloulme Jean Christophe , Delalande François , Stuber Denise , Sage Dominique , Van Dorsselaer Alain , Poisbeau Pierrick , Aunis Dominique , Goumon Yannick 
Published: March 2011

AbstractEndogenous morphine, morphine‐6‐glucuronide, and codeine, which are structurally identical to vegetal alkaloids, can be synthesized by mammalian cells from dopamine. However, the role of brain endogenous morphine and its derivative compounds is a matter of debate, and knowledge about its distribution is lacking. In this study, by using a validated antibody, we describe a precise mapping of endogenous morphine‐like compounds (morphine and/or its glucuronides and/or codeine) in the mouse brain. First, a mass spectrometry approach confirmed the presence of morphine and codeine in mouse brain, but also, of morphine‐6‐glucuronide and morphine‐3‐glucuronide representing two metabolites of morphine. Second, light microscopy allowed us to observe immunopositive cell somas and cytoplasmic processes throughout the mouse brain. Morphine‐like immunoreactivity was present in various structures including the hippocampus, olfactory bulb, band of Broca, basal ganglia, and cerebellum. Third, by using confocal microscopy and immunofluroscence co‐localization, we characterized cell types containing endogenous opiates. Interestingly, we observed that morphine‐like immunoreactivity throughout the encephalon is mainly present in γ‐aminobutyric acid (GABA)ergic neurons. Astrocytes were also labeled throughout the entire brain, in the cell body, in the cytoplasmic processes, and in astrocytic feet surrounding blood vessels. Finally, ultrastructural localization of morphine‐like immunoreactivity was determined by electron microscopy and showed the presence of morphine‐like label in presynaptic terminals in the cerebellum and postsynaptic terminals in the rest of the mouse brain. In conclusion, the presence of endogenous morphine‐like compounds in brain regions not usually involved in pain modulation opens the exciting opportunity to extend the role and function of endogenous alkaloids far beyond their analgesic functions. J. Comp. Neurol. 519:2390–2416, 2011. © 2011 Wiley‐Liss, Inc.
Neural cell adhesion molecule ablation in mice causes hippocampal dysplasia and loss of septal cholinergic neurons
Authors: Tereshchenko Yuliya , Morellini Fabio , Dityatev Alexander , Schachner Melitta , Irintchev Andrey 
Published: March 2011

AbstractThe neural cell adhesion molecule (NCAM) is implicated in nervous system development and plasticity. In humans, abnormal NCAM expression has been linked to the pathogenesis of neuropsychiatric and neurodegenerative disorders accompanied by cognitive dysfunctions. Impaired cognition is also observed in NCAM‐deficient (NCAM−/−) mice. Considering the importance of the septal cholinergic nuclei and the hippocampus for cognition, we performed quantitative morphological analyses of these areas in young and adult (2 and 13 months old, respectively) NCAM−/− mice and wild‐type (NCAM+/+) littermates. In young mice, we found lower numbers of septal cholinergic neurons in NCAM−/− than in NCAM+/+ mice. Despite deficient numbers of neurons, total lengths of cholinergic axons and choline acetyltransferase protein levels in the hippocampus of NCAM−/− mice were normal. The hippocampus of NCAM−/− mice was atrophic, notably in the CA3 subfield and the dentate gyrus (DG). The atrophy appeared to have different primary causes in the two subfields: loss of pyramidal cells in CA3 and reduced branching and volume of granule cell dendrites in the DG. The frequency of dendritic spines on dentate granule cells in NCAM−/− mice was normal. Numbers of parvalbumin‐positive (PV+) interneurons were reduced in NCAM−/− mice in proportion to subfield volume loss, and the ratios of principal cells to PV+ interneurons were similar to those of NCAM+/+ mice. None of the observed abnormalities was exaggerated or alleviated in adult NCAM−/− mice. Our observations indicate that NCAM ablation causes structural abnormalities in the hippocampus and the forebrain cholinergic system in adult mice, which may contribute to impaired cognition in NCAM−/− mice. J. Comp. Neurol. 519:2475–2492, 2011. © 2011 Wiley‐Liss, Inc.
Sensory neuroanatomy of Parastrongyloides trichosuri, a nematode parasite of mammals: Amphidial neurons of the first‐stage larva
Authors: Zhu He , Li Jian , Nolan Thomas J. , Schad Gerhard A. , Lok James B. 
Published: March 2011

AbstractOwing to its ability to switch between free‐living and parasitic modes of development, Parastrongyloides trichosuri represents a valuable model with which to study the evolution of parasitism among the nematodes, especially aspects pertaining to morphogenesis of infective third‐stage larvae. In the free‐living nematode Caenorhabditis elegans, developmental fates of third‐stage larvae are determined in part by environmental cues received by chemosensory neurons in the amphidial sensillae. As a basis for comparative study, we have described the neuroanatomy of the amphidial sensillae of P. trichosuri. By using computational methods, we incorporated serial electron micrographs into a three‐dimensional reconstruction of the amphidial neurons of this parasite. Each amphid is innervated by 13 neurons, and the dendritic processes of 10 of these extend nearly to the amphidial pore. Dendritic processes of two specialized neurons leave the amphidial channel and terminate within invaginations of the sheath cell. One of these is similar to the finger cell of C. elegans, terminating in digitiform projections. The other projects a single cilium into the sheath cell. The dendritic process of a third specialized neuron terminates within the tight junction of the amphid. Each amphidial neuron was traced from the tip of its dendrite(s) to its cell body in the lateral ganglion. Positions of these cell bodies approximate those of morphologically similar amphidial neurons in Caenorhabditis elegans, so the standard nomenclature for amphidial neurons in C. elegans was adopted. A map of cell bodies within the lateral ganglion of P. trichosuri was prepared to facilitate functional study of these neurons. J. Comp. Neurol. 519:2493–2507, 2011. © 2011 Wiley‐Liss, Inc.
Ontogeny of sex differences in response to novel objects from adolescence to adulthood in lister‐hooded rats
Authors: Cyrenne De‐Laine M. , Brown Gillian R. 
Published: March 2011

AbstractIn humans, novelty‐seeking behavior peaks in adolescence and is higher in males than females. Relatively, little information is available regarding age and sex differences in response to novelty in rodents. In this study, male and female Lister‐hooded rats were tested at early adolescence (postnatal day, pnd, 28), mid‐adolescence (pnd 40), or early adulthood (pnd 80) in a novel object recognition task (n = 12 males/females per age group). Males displayed a higher preference for the novel object than females at mid‐adolescence, with no sex difference at early adolescence. Adult females interacted with the novel object more than adult males, but not when side biases were removed. Sex differences at mid‐adolescence were not found in other measures, suggesting that the difference at this age was specific to situations involving choice of novelty. The results are considered in the context of age‐ and sex‐dependent interactions between gonadal hormones and the dopamine system. © 2011 Wiley Periodicals, Inc. Dev Psychobiol 53:670–676, 2011.
Control of pelvic girdle development by genes of the Pbx family and Emx2
Authors: Capellini Terence D. , Handschuh Karen , Quintana Laura , Ferretti Elisabetta , Di Giacomo Giuseppina , Fantini Sebastian , Vaccari Giulia , Clarke Shoa L. , Wenger Aaron M. , Bejerano Gill , Sharpe James , Zappavigna Vincenzo , Selleri Licia 
Published: March 2011

AbstractGenes expressed in the somatopleuric mesoderm, the embryonic domain giving rise to the vertebrate pelvis, appear important for pelvic girdle formation. Among such genes, Pbx family members and Emx2 were found to genetically interact in hindlimb and pectoral girdle formation. Here, we generated compound mutant embryos carrying combinations of mutated alleles for Pbx1, Pbx2, and Pbx3, as well as Pbx1 and Emx2, to examine potential genetic interactions during pelvic development. Indeed, Pbx genes share overlapping functions and Pbx1 and Emx2 genetically interact in pelvic formation. We show that, in compound Pbx1;Pbx2 and Pbx1;Emx2 mutants, pelvic mesenchymal condensation is markedly perturbed, indicative of an upstream control by these homeoproteins. We establish that expression of Tbx15, Prrx1, and Pax1, among other genes involved in the specification and development of select pelvic structures, is altered in our compound mutants. Lastly, we identify potential Pbx1‐Emx2–regulated enhancers for Tbx15, Prrx1, and Pax1, using bioinformatics analyses. Developmental Dynamics 240:1173–1189, 2011. © 2011 Wiley‐Liss, Inc.
Loss of Lrp2 in zebrafish disrupts pronephric tubular clearance but not forebrain development
Authors: Kur Esther , Christa Anna , Veth Kerry N. , Gajera Chandresh R. , Andrade‐Navarro Miguel A. , Zhang Jingjing , Willer Jason R. , Gregg Ronald G. , Abdelilah‐Seyfried Salim , Bachmann Sebastian , Link Brian A. , Hammes Annette , Willnow Thomas E. 
Published: March 2011

AbstractLow‐density lipoprotein receptor‐related protein 2 (LRP2) is a multifunctional cell surface receptor conserved from nematodes to humans. In mammals, it acts as regulator of sonic hedgehog and bone morphogenetic protein pathways in patterning of the embryonic forebrain and as a clearance receptor in the adult kidney. Little is known about activities of this LRP in other phyla. Here, we extend the functional elucidation of LRP2 to zebrafish as a model organism of receptor (dys)function. We demonstrate that expression of Lrp2 in embryonic and larval fish recapitulates the patterns seen in mammalian brain and kidney. Furthermore, we studied the consequence of receptor deficiencies in lrp2 and in lrp2b, a homologue unique to fish, using ENU mutagenesis or morpholino knockdown. While receptor‐deficient zebrafish suffer from overt renal resorption deficiency, their brain development proceeds normally, suggesting evolutionary conservation of receptor functions in pronephric duct clearance but not in patterning of the teleost forebrain. Developmental Dynamics 240:1567–1577, 2011. © 2011 Wiley‐Liss, Inc.
Recent Advances in the Synthesis of Fluorinated Amino Acids
Authors: Qiu Xiao‐Long , Qing Feng‐Ling 
Published: March 2011

AbstractIntroduction of fluorine atoms or fluorine‐containing groups into amino acids has attracted much attention from bioorganic and medicinal chemists because the resulting fluorinated amino acids have found wide application as potential enzyme inhibitors and antitumor (antibacterial) agents. Additionally, it is well known that replacement of naturally occurring amino acid(s) in some peptide chains with their fluorinated counterparts can significantly increase specific protein–ligand or protein–protein interactions, leading to increases in the proteolytic and thermal stabilities of peptide compounds and, as a result, promote their therapeutic properties. This microreview summarizes important advances in the synthesis of fluorinated amino acids since 2005. The contents are simply divided into three groups on the basis of amino acid types: fluorinated α‐amino acids (F‐αAAs), fluorinated β‐amino acids (F‐βAAs), and fluorinated cyclic amino acids (F‐CAAs).
Controlling retention, selectivity and magnitude of EOF by segmented monolithic columns consisting of octadecyl and naphthyl monolithic segments – applications to RP‐CEC of both neutral and charged solutes
Authors: Karenga Samuel , Rassi Ziad El 
Published: March 2011

AbstractMonolithic capillaries made of two adjoining segments each filled with a different monolith were introduced for the control and manipulation of the electroosmotic flow (EOF), retention and selectivity in reversed phase‐capillary electrochromatography (RP‐CEC). These columns were called segmented monolithic columns (SMCs) where one segment was filled with a naphthyl methacrylate monolith (NMM) to provide hydrophobic and π‐interactions, while the other segment was filled with an octadecyl acrylate monolith (ODM) to provide solely hydrophobic interaction. The ODM segment not only provided hydrophobic interactions but also functioned as the EOF accelerator segment. The average EOF of the SMC increased linearly with increasing the fractional length of the ODM segment. The neutral SMC provided a convenient way for tuning EOF, selectivity and retention in the absence of annoying electrostatic interactions and irreversible solute adsorption. The SMCs allowed the separation of a wide range of neutral solutes including polycyclic aromatic hydrocarbons (PAHs) that are difficult to separate using conventional alkyl‐bonded stationary phases. In all cases, the k′ of a given solute was a linear function of the fractional length of the ODM or NMM segment in the SMCs, thus facilitating the tailoring of a given SMC to solve a given separation problem. At some ODM fractional length, the fabricated SMC allowed the separation of charged solutes such as peptides and proteins that could not otherwise be achieved on a monolithic column made from NMM as an isotropic stationary phase due to the lower EOF exhibited by this monolith.
Variation in aroma release between panellists consuming different types of confectionary
Authors: Blee Nicola , Linforth Robert , Yang Nicole , Brown Keith , Taylor Andrew 
Published: March 2011

ABSTRACTVariation in in vivo volatile release was studied using atmospheric pressure chemical ionization–mass spectrometry. The extent of variation in in vivo flavour release was related to the partitioning behaviour of the compound. Compounds with highest air/water partition coefficients (Kaw) showed more variation in release than those with low Kaw values. Sample matrix components (such as lipid) have the potential to influence the air/product partition coefficient. If they reduce the partition coefficient they can reduce the variation in volatile release. Variation in release was assessed for menthone from a series of five different sample types. Chewing gum gave the most consistent release, which was attributed to the consistency of chewing in oral processing and volatile delivery. The least consistent release intensity was associated with the boiled sweet, which may have resulted in substantial variation in oral processing and hence volatile delivery. A study of a panel of 50 people showed that there were strong correlations in the intensity of volatile release across sample types. Panellists who released high concentrations of volatiles into their breath from one sample type would typically do so for another. Equally, panellists who released lower amounts from one sample type would also release less from others. Some differences in the intensity of aroma release were observed between sample types. These appear to be related to textural differences between samples, which would affect oral processing. Copyright © 2011 John Wiley & Sons, Ltd.
Im Reich des Steinbocks
Authors: Klimscha Florian , Siegel Ulrike , Eichmann Ricardo , Schmidt Klaus 
Published: March 2011

AbstractFern der bekannten Ausgrabungsstätten legen internationale Archäologenteams im jordanischen Tall Hujayrat al‐Ghuzlan die Überreste chalkolithischer Siedlungen frei. Ihre Funde sind voller Überraschungen – sie zeigen, wie Kulturen und Techniken von den Metropolen in die Provinz ausstrahlten.
Spontaneous blood oxygenation level‐dependent fMRI signal is modulated by behavioral state and correlates with evoked response in sensorimotor cortex: A 7.0‐T fMRI study
Authors: Donahue Manus J. , Hoogduin Hans , Smith Stephen M. , Siero Jeroen C.W. , Chappell Michael , Petridou Natalia , Jezzard Peter , Luijten Peter R. , Hendrikse Jeroen 
Published: March 2011

AbstractSynchrony measurements of spontaneous low‐frequency blood oxygenation level‐dependent (BOLD) fluctuations are increasingly being used to investigate spatial regions of functional connectivity. Although information regarding BOLD–BOLD synchrony between different regions is frequently reported, the relationship between spontaneous activity and behavioral state, and the association of spontaneous signal synchrony and evoked response, are less well characterized. The purpose of this study is to exploit the higher signal‐to‐noise ratio and in turn available spatial resolution at 7.0 T to understand the relationship between synchrony, measured as Pearson's R value, and amplitude, measured as signal standard deviation over time, in sensorimotor cortex for four separate behavioral states: eyes closed resting (EC), eyes open fixation (EO), EO with constant right hand fist clench (EO‐F) and EO with 6 s off/6 s on (0.083 Hz) right hand finger tapping (EO‐T). BOLD (TE/TR = 25/3,000 ms; 100 time points) scans were performed in healthy volunteers (7.0 T; 4 M/3 F; right‐handed) at high spatial resolution = 1.6 × 1.6 × 1.6 mm3. Results (z > 5; P < 0.05; low‐pass filtering <0.067 Hz) reveal that synchrony is highest in the EC state (R = 0.35 ± 0.07) and reduces for EO (R = 0.26 ± 0.07), EO‐F (R = 0.23 ± 0.07; P < 0.05), and EO‐T (R = 0.12 ± 0.04; P < 0.05) conditions. Amplitude was highest in the EC condition and only reduced significantly (P < 0.05) for the EO‐T condition. Synchrony within sensorimotor cortex correlated with evoked finger‐tapping response magnitude (R = 0.81; P = 0.03), suggesting that spontaneous signal synchrony may be a predictor of evoked BOLD response magnitude and may account for intersubject variability in sensorimotor cortex. Hum Brain Mapp, 2012. © 2011 Wiley Periodicals, Inc.