bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rho GTPases Mediate the Mechanosensitive Lineage Commitment of Neural Stem Cells
Authors: Keung Albert J. , de Juan-Pardo Elena M. , Schaffer David V. , Kumar Sanjay 
Published: September 2011

Abstract
Adult neural stem cells (NSCs) play important roles in learning and memory and are negatively impacted by neurological disease. It is known that biochemical and genetic factors regulate self-renewal and differentiation, and it has recently been suggested that mechanical and solid-state cues, such as extracellular matrix (ECM) stiffness, can also regulate the functions of NSCs and other stem cell types. However, relatively little is known of the molecular mechanisms through which stem cells transduce mechanical inputs into fate decisions, the extent to which mechanical inputs instruct fate decisions versus select for or against lineage-committed blast populations, or the in vivo relevance of mechanotransductive signaling molecules in native stem cell niches. Here we demonstrate that ECM-derived mechanical signals act through Rho GTPases to activate the cellular contractility machinery in a key early window during differentiation to regulate NSC lineage commitment. Furthermore, culturing NSCs on increasingly stiff ECMs enhances RhoA and Cdc42 activation, increases NSC stiffness, and suppresses neurogenesis. Likewise, inhibiting RhoA and Cdc42 or downstream regulators of cellular contractility rescues NSCs from stiff matrix- and Rho GTPase-induced neurosuppression. Importantly, Rho GTPase expression and ECM stiffness do not alter proliferation or apoptosis rates indicating that an instructive rather than selective mechanism modulates lineage distributions. Finally, in the adult brain, RhoA activation in hippocampal progenitors suppresses neurogenesis, analogous to its effect in vitro. These results establish Rho GTPase-based mechanotransduction and cellular stiffness as biophysical regulators of NSC fate in vitro and RhoA as an important regulatory protein in the hippocampal stem cell niche.
Brief Report: Phenotypic Rescue of Induced Pluripotent Stem Cell-Derived Motoneurons of a Spinal Muscular Atrophy Patient
Authors: Chang Tammy , Zheng Weiyan , Tsark Walter , Bates Steven , Huang He , Lin Ren-Jang , Yee Jiing-Kuan 
Published: September 2011

Abstract
Spinal muscular atrophy (SMA) is one of the most common autosomal recessive disorders in humans and is a common genetic cause of infant mortality. The disease is caused by loss of the survival of motoneuron (SMN) protein, resulting in the degeneration of alpha motoneurons in spinal cord and muscular atrophy in the limbs and trunk. One function of SMN involves RNA splicing. It is unclear why a deficiency in a housekeeping function such as RNA splicing causes profound effects only on motoneurons but not on other cell types. One difficulty in studying SMA is the scarcity of patient's samples. The discovery that somatic cells can be reprogrammed to become induced pluripotent stem cell (iPSCs) raises the intriguing possibility of modeling human diseases in vitro. We reported the establishment of five iPSC lines from the fibroblasts of a type 1 SMA patient. Neuronal cultures derived from these SMA iPSC lines exhibited a reduced capacity to form motoneurons and an abnormality in neurite outgrowth. Ectopic SMN expression in these iPSC lines restored normal motoneuron differentiation and rescued the phenotype of delayed neurite outgrowth. These results suggest that the observed abnormalities are indeed caused by SMN deficiency and not by iPSC clonal variability. Further characterization of the cellular and functional deficits in motoneurons derived from these iPSCs may accelerate the exploration of the underlying mechanisms of SMA pathogenesis.
Concise Review: Transmissible Animal Tumors as Models of the Cancer Stem-Cell Process
Authors: O'Neill Iain D. 
Published: September 2011

Abstract
Tasmanian devil facial tumor disease (DFTD) and canine transmissible venereal tumor (CTVT) are highly unusual cancers capable of being transmitted between animals as an allograft. The concept that these tumors represent a cancer stem-cell process has never been formally evaluated. For each, evidence of self-renewal is found in the natural history of these tumors in the wild, tumor initiation in recipient animals, and serial transplantation studies. Additional data for stem-cell-specific genes and markers in DFTD also exist. Although both tumor types manifest as undifferentiated cancers, immunocytohistochemistry supports a histiocytic phenotype for CTVT and a neural crest origin, possibly a Schwann-cell phenotype, for DFTD. In these data, differential expression of lineage markers is seen which may suggest some capacity for differentiation toward a heterogeneous variety of cell types. It is proposed that DFTD and CTVT may represent and may serve as models of the cancer stem-cell process, but formal investigation is required to clarify this. Appreciation of any such role may act as a stimulus to ongoing research in the pathology of DFTD and CTVT, including further characterization of their origin and phenotype and possible therapeutic approaches. Additionally, they may provide valuable models for future studies of their analogous human cancers, including any putative CSC component.
Dopamine agonist radioligand binds to both D2High and D2Low receptors, explaining why alterations in D2High are not detected in human brain scans
Authors: Seeman Philip 
Published: September 2011

AbstractThe features of schizophrenia are consistent with increased sensitivity to endogenous dopamine. Animal models of schizophrenia reveal an increase in the in vitro proportion of striatal dopamine D2 receptors in the high‐affinity state for dopamine (i.e., D2High), as measured by dopamine/[3H]domperidone competition. However, in vivo studies did not reveal the dopamine agonist [11C](+)PHNO to be elevated in amphetamine‐sensitized rats. Also, no increase was found in the in vivo binding of [11C](+)PHNO in schizophrenia patients. This work was done to resolve the contradictory findings. It was found that the in vitro density of rat striatal D2 receptors was 18 pmol/g for [3H]raclopride and 12 pmol/g for [3H](+)PHNO; most of the latter sites disappeared in the presence of guanine nucleotide. Using 2 nM [3H](+)PHNO (Kd of 0.72 nM at D2) to label D2 receptors in the striata and the human D2 clone, 10 nM to 100 nM dopamine inhibited 10–20% of the [3H](+)PHNO bound, representing high‐affinity binding of [3H](+)PHNO, with the remainder inhibited above 100 nM dopamine, representing low‐affinity binding of [3H](+)PHNO. It was found that (+)PHNO and (−)NPA dissociated from the D2 clone with half‐times of 96 and 600 s, respectively. These rates are slower than the reported sub‐second dissociation of the G protein from a receptor, suggesting that these two ligands still occupy the D2Low receptor after the G protein has separated. Thus, the radio‐agonist label for (+)PHNO is not selective for dopamine D2High receptors, but also binds to the D2Low state of the dopamine receptor. Synapse, 2012. © 2011 Wiley Periodicals, Inc.
A new automatic algorithm to extract craniofacial measurements from fetal three‐dimensional volumes
Authors: Tsai P.‐Y. , Chen H.‐C. , Huang H.‐H. , Chang C.‐H. , Fan P.‐S. , Huang C.‐I. , Cheng Y.‐C. , Chang F.‐M. , Sun Y.‐N. 
Published: September 2011

AbstractObjectivesThree‐dimensional (3D) ultrasound is useful in the prenatal evaluation of fetal craniofacial structures, particularly as it provides a multiplanar view. However, an expert must designate the area of interest and the appropriate view, making measurement of fetal structures using 3D ultrasound both time‐consuming and subjective. In this study we propose an image analysis system that measures automatically and precisely the fetal craniofacial structures and evaluate its performance in the second trimester of pregnancy using a new 3D volume analysis algorithm.MethodsA universal facial surface template model containing the geometric shape information of a fetal craniofacial structure was constructed from a fetal phantom. Using the proposed image analysis system we fitted this stored template model using a model deformation approach to individual fetal 3D facial volumes from 11 mid‐trimester fetuses, and extracted automatically the following standard measurements: biparietal diameter (BPD), occipitofrontal diameter (OFD), interorbital diameter (IOD), bilateral orbital diameter (BOD) and distance between vertex and nasion (VN). The same five parameters were measured manually by an expert and the results compared.ResultsComparison of the algorithm‐based automatic measurements with manual measurements made by an expert gave correlation coefficients of 0.99 for BPD, 0.98 for OFD, 0.80 for BOD, 0.83 for IOD and 0.99 for VN. There were no significant differences between automatic and manual measurements.ConclusionOur proposed system measures precisely the fetal craniofacial structures using 3D ultrasound, making it potentially useful for clinical service. This system could also be applied to other clinical fields in future testing. Copyright © 2012 ISUOG. Published by John Wiley & Sons, Ltd.
Comparison between prenatal ultrasound and postmortem findings in fetuses and infants with developmental anomalies
Authors: Vogt C. , Blaas H.‐G. K. , Salvesen K. Å. , Eik‐Nes S. H. 
Published: September 2011

AbstractObjectiveTo determine if postmortem examinations of fetuses and infants change the diagnosis obtained at prenatal ultrasound and affect counseling of future pregnancies, and if there has been a change over recent years in the accuracy of prenatal ultrasound diagnosis.MethodsThis was a retrospective review of 455 autopsies of fetuses and infants with developmental anomalies performed at Trondheim University Hospital between 1995 and 2004 and with a prenatal ultrasound examination performed at a tertiary referral center. The routine ultrasound examinations were performed by specially trained midwives and obstetricians, referral scans by fetal medicine experts and autopsies by consultant pathologists with experience in perinatal pathology. The results of this study were also compared with those of a previous similar study performed between 1985 and 1995, with fetuses and infants coming from the same population and diagnosed at the same center.ResultsOf all cases analyzed during the study period, there was complete agreement between prenatal ultrasound and postmortem findings in 84% (384/455), i.e. prenatal ultrasound diagnoses were supplemented by postmortem examinations in 16% (71/455). Autopsy findings in four of these cases influenced further counseling. There was agreement regarding the main diagnosis in 98% (445/455) of cases. In the previous 10‐year period, there was complete agreement in 75% and the main diagnosis was correct in 90% of cases. These differences between the two time periods were statistically significant (P = 0.0004 and P < 0.0001, respectively). The most frequent defects involved the central nervous system, heart and urinary tract. For these defects, detection rates for the main diagnoses were significantly better in 1995–2004 compared with in the previous 10‐year period (P = 0.0125, P = 0.0111 and P = 0.0241, respectively).ConclusionThe accuracy of prenatal sonographic detection of developmental anomalies has increased in recent years. However, postmortem examination is still necessary to verify or improve the prenatal diagnosis and may influence future counseling. Copyright © 2012 ISUOG. Published by John Wiley & Sons, Ltd.
Structure of transfer RNAs: similarity and variability
Authors: Giegé Richard , Jühling Frank , Pütz Joern , Stadler Peter , Sauter Claude , Florentz Catherine 
Published: September 2011

AbstractTransfer RNAs (tRNAs) are ancient molecules whose origin goes back to the beginning of life on Earth. Key partners in the ribosome‐translation machinery, tRNAs read genetic information on messenger RNA and deliver codon specified amino acids attached to their distal 3′‐extremity for peptide bond synthesis on the ribosome. In addition to this universal function, tRNAs participate in a wealth of other biological processes and undergo intricate maturation events. Our understanding of tRNA biology has been mainly phenomenological, but ongoing progress in structural biology is giving a robust physico‐chemical basis that explains many facets of tRNA functions. Advanced sequence analysis of tRNA genes and their RNA transcripts have uncovered rules that underly tRNA 2D folding and 3D L‐shaped architecture, as well as provided clues about their evolution. The increasing number of X‐ray structures of free, protein‐ and ribosome‐bound tRNA, reveal structural details accounting for the identity of the 22 tRNA families (one for each proteinogenic amino acid) and for the multifunctionality of a given family. Importantly, the structural role of post‐transcriptional tRNA modifications is being deciphered. On the other hand, the plasticity of tRNA structure during function has been illustrated using a variety of technical approaches that allow dynamical insights. The large range of structural properties not only allows tRNAs to be the key actors of translation, but also sustain a diversity of unrelated functions from which only a few have already been pinpointed. Many surprises can still be expected. WIREs RNA 2012, 3:37–61. doi: 10.1002/wrna.103This article is categorized under:

RNA Structure and Dynamics > RNA Structure, Dynamics, and Chemistry
RNA Processing > tRNA Processing
Preparation, Crystal Structure, and Thermal Decomposition of Two Novel Energetic Compounds [Ni(IMI)6](L)2 (L = ClO4– and NO3–) and one Carbonate Compound [Ni(IMI)6](CO3)·5H2O (IMI = Imidazole)
Authors: Wu Bi‐Dong , Wang Shi‐Wei , Yang Li , Zhang Tong‐Lai , Zhang Jian‐Guo , Zhou Zun‐Ning 
Published: September 2011

AbstractThree novel multi‐ligand coordination compounds, namely [Ni(IMI)6](ClO4)2 (1), [Ni(IMI)6](NO3)2 (2), and [Ni(IMI)6](CO3)·5H2O (3) were synthesized and characterized by elemental analysis and FT‐IR spectroscopy. The crystal structures were determined by X‐ray single crystal diffraction. The title compounds crystallize monoclinically, rhombohedrally, and hexagonally, and belong to space groups P21/m, R3, and P63/m, respectively. The nickel(II) ions are hexacoordinated to six imidazole molecules by the nitrogen atoms. The thermal decomposition mechanisms of compounds 1 and 2 were studied by using differential scanning calorimetry (DSC) and thermogravimetry‐derivative thermogravimetry (TG‐DTG) techniques. The thermal decompositions were carried out in a nitrogen atmosphere with a heating rate of 10 K·min–1 and contain one endothermic process between 350 K and 500 K and one main exothermic process between 500 K and 800 K in the DSC curves. In addition, the non‐isothermal kinetical parameters were calculated by using Kissinger's and Ozawa's method, respectively. The energies of combustion and the enthalpies of formation were measured and calculated, and the results indicated that both compounds have good combustion performance. The sensitivities were also determined with standard methods. The results showed that [Ni(IMI)6](L)2 compounds have a potential application as energetic materials.
A Novel Heterometallic 3d–4f Complex with an Unusual [MnIV4Nd4O4] Core Topology
Authors: Hallier Kirstin , Hołyńska Małgorzata , Dehnen Stefanie 
Published: September 2011

AbstractThe complex [Mn4Nd4O4(Me‐sao)6(NO3)4(OMe)4(MeOH)2] (1) with an unprecedented [MnIV4Nd4O4] core topology was synthesized from MnCl2, Nd(NO3)3 and Me‐saoH2 in methanol at basic conditions (Me‐saoH2 = 2′‐hydroxyacetophenoxime). In 1 MnIV and NdIII ions are bridged by oxido and methoxido ligands to form an unusual topology including two distorted tetrahedral [Nd2Mn2(μ4‐O)] units. 1 crystallizes in the monoclinic space group P21/c with Z = 2 and lattice constants (at 100 K) a = 14.142(4), b = 19.365(5), c = 14.637(4) Å, β = 90.32(3)°.
Synthesis and Characterization of Gold(III) Complexes Bearing a Picoline‐functionalized N‐Heterocyclic Carbene
Authors: Topf Christoph , Hirtenlehner Christa , Fleck Michel , List Manuela , Monkowius Uwe 
Published: September 2011

Abstract3‐Methyl‐1‐(2‐picolyl)‐imidazolium chloride (1) has been synthesized and used as a precursor for the preparation of the (NHC)AgCl complex [NHC = 3‐methyl‐1‐(2‐picolyl)imidazol‐2‐ylidene] (2). Transmetalation of 2 with (tht)AuBr (tht = tetrahydrothiophene) yields the corresponding (NHC)AuBr complex 3, which is further oxidized by Br2 to give the (NHC)AuBr3 compound 4. Treatment of 4 with one equivalent of solid AgBF4 affords the [(NHC)AuBr2][BF4] congener 5 as a pale green, crystalline powder. The structure of 4 and 5 were determined by single‐crystal X‐ray diffraction, revealing for 5 a κ‐N‐coordination of the AuIII atom by the picolyl nitrogen atom. Further attempts to exchange all bromides by carboxylates results in the reduction to the dimeric AuI compound [(NHC)2Au2][BF4]2, 6.
Organoelement Complexes of a Dinucleating Double β‐Diiminato Ligand – Precedent Cases from Groups 1, 2, and 13
Authors: Falkenhagen Jan P. , Haack Peter , Limberg Christian , Braun Beatrice 
Published: September 2011

AbstractMain group chemistry of dinucleating ligands based on a xanthene backbone and two parallel diiminato binding sites (Xanthdim) has been investigated. To complement studies concerning the coordination modes adopted by Xanthdim in combination with alkali metal ions a di‐rubidium complex with toluene co‐ligands has been prepared. Its structural parameters lie in between those previously observed for corresponding K+ and Cs+ complexes. Furthermore, the complexes [Xanthdim](MgMe(thf))2 (2) and [Xanthdim](MgBr(thf))2 (3) were synthesised by reaction of [Xanthdim](K(thf)2)2 and [Xanthdim]H2, respectively, with MeMgBr. Both compounds proved stable against ligand exchange according to the Schlenk equilibrium. After reaction of [Xanthdim]H2 and [Xanthdim]H2, respectively, with AlMe3 the complexes [Xanthdim](AlMe2)2 (4) and [Xanthdim](AlMe2)2 (5) were isolated and fully characterised. They were found to be dynamic in solution and Al–CH3···F‐aryl interactions were detected in case of 5. The solid‐state structures and NMR spectroscopic properties of all compounds were determined and analysed.
Prognostic Factors of Papillary Thyroid Carcinoma Vary According to Sex and Patient Age
Authors: Ito Yasuhiro , Kudo Takumi , Takamura Yuuki , Kobayashi Kaoru , Miya Akihiro , Miyauchi Akira 
Published: September 2011

AbstractBackgroundWe previously showed that preoperative and intraoperative evaluations of papillary thyroid carcinoma (PTC) are important for predicting a patient’s prognosis, and we identified several prognostic factors. In this study, we investigated differences in the significance of these factors according to patient age and sex.MethodsA total of 5768 PTC patients (608 men, 5160 women) without distant metastasis at diagnosis who underwent initial surgery between 1987 and 2004 in Kuma Hospital were enrolled in this study. The postoperative follow‐up period was 129 months (10.8 years) on average.ResultsWe examined variations in the prognostic significance of tumor size >4 cm (T), extrathyroid extension (Ex), node metastasis >3 cm (N), and extranodal (tumor extension (LN‐Ex)—which were identified as prognostic factors in our previous studies—in four subsets of patients based on age and sex. In older women, Ex was the most significant prognostic factor for local and distant recurrences and carcinoma death. In older men as well, Ex was a strong prognostic factor, but N had a prognostic impact similar to Ex for local recurrence and LN‐Ex was the strongest prognostic factor for carcinoma death. N was the most significant prognostic factor for local and distant recurrences and carcinoma death in younger women. T and N independently affected local recurrence with similar significance, and Ex was the only independent prognostic factor for distant recurrence in younger men. Because only two of the younger men in this series died of carcinoma, we could not analyze prognostic factors for carcinoma death in this subgroup.ConclusionsThe significance of prognostic factors of PTC varied according to patient sex and age, which might contribute not only to evaluating the prognosis but also to deciding therapeutic strategies for each patient. Because Ex was a prominent prognostic factor for local and distant recurrences in older patients, careful and extensive excision of the site of carcinoma extension and extensive lymph node dissection should be performed, especially for older patients with Ex.
Indications for Staging Laparoscopy in Clinical T4M0 Gastric Cancer
Authors: Tsuchida Kazuhito , Yoshikawa Takaki , Tsuburaya Akira , Cho Haruhiko , Kobayashi Osamu 
Published: September 2011

AbstractBackgroundThis study was undertaken to determine the efficacy of the clinical indications for performing staging laparoscopy for locally advanced gastric cancer to detect peritoneal metastasis or positive cytology findings.MethodsThe study included 231 patients with T4 gastric cancer without hematogenous or clinically evident peritoneal metastasis. The clinicopathologic features, including T and N factors, were diagnosed by clinical staging. The relation between the clinicopathologic features and the presence of peritoneal metastasis or lavage cytology at surgery was analyzed.ResultsA total of 31 patients underwent staging laparoscopy; 200 others underwent open surgery as a primary treatment. Both peritoneal metastasis and lavage cytology were negative in 145 (62.8%) patients, whereas peritoneal metastasis or lavage cytology was positive in 86 patients (37.2%). When calculating diagnostic accuracy in the 23 patients who underwent open laparotomy after staging laparoscopy, the accuracy rate was 95.7%. A multivariate analysis showed that a tumor location involving three portions; macroscopic type 3, 4, or 5; and positive lymph node metastasis to all three is significantly correlated with either peritoneal metastasis or positive cytology. When patients had two or three factors among these three independent risk factors, peritoneal metastasis or positive cytology could be detected with 91.9% sensitivity and 46.7% positive predictive value.ConclusionsThe selection of T4 tumors based on clinically evaluable risk factors is therefore considered useful for detecting peritoneal metastasis efficiently and hence avoiding unnecessary staging laparoscopy.
The Utility of a Noninvasive 13C‐Acetate Breath Test to Predict Quality of Life After Gastrectomy
Authors: Toyomasu Yoshitaka , Mochiki Erito , Ando Hiroyuki , Ohno Tetsuro , Kamiyama Yoichi , Kuwano Hiroyuki 
Published: September 2011

AbstractBackgroundThe radioscintigraphic technique has been accepted as the standard by which to measure gastric emptying but it is invasive and expensive. A 13C‐acetate breath test was reported to be a noninvasive and reliable method. The aim of this study was to investigate the accuracy of a 13C‐acetate breath test in reflecting gastric function and the relationship between food intake and change in body weight after distal gastrectomy.MethodsTwenty‐five patients who had undergone curative distal gastrectomy with Billroth‐I reconstruction for gastric cancer and ten healthy volunteers were included in the study. The gastrectomy group was divided into two groups: the stasis group and the nonstasis group. The breath test was performed on the patients with gastrectomy and the healthy volunteers, and the time lag between ingestion and the peak of 13CO2 expiration (T lag) was calculated. The manometry study was performed on the patients who underwent gastrectomy and the motility index (MI) was calculated. The relationships between T lag and food intake and body weight were examined.ResultsThe T lag was significantly shorter in the nonstasis group than in the stasis group. The MI in the duodenum in the nonstasis group was significantly larger than that in the stasis group. There was significant correlation between T lag and food intake, but no significant correlation between T lag and body weight.ConclusionThe 13C‐acetate breath test might be useful not only for the evaluation of the function of the remnant stomach, but also for the prediction of postoperative status.