bluuebunny/crossref_metadata_2025_split huggingface dataset:
Src‐dependent Tks5 phosphorylation regulates invadopodia‐associated invasion in prostate cancer cells
Authors: Burger Karen L. , Learman Brian S. , Boucherle Amy K. , Sirintrapun S. Joseph , Isom Scott , Díaz Begoña , Courtneidge Sara A. , Seals Darren F. 
Published: October 2013

AbstractBACKGROUNDThe Src tyrosine kinase substrate and adaptor protein Tks5 had previously been implicated in the invasive phenotype of normal and transformed cell types via regulation of cytoskeletal structures called podosomes/invadopodia. The role of Src‐Tks5 signaling in invasive prostate cancer, however, had not been previously evaluated.METHODSWe measured the relative expression of Tks5 in normal (n = 20) and cancerous (n = 184, from 92 patients) prostate tissue specimens by immunohistochemistry using a commercially available tumor microarray. We also manipulated the expression and activity of wild‐type and mutant Src and Tks5 constructs in the LNCaP and PC‐3 prostate cancer cell lines in order to ascertain the role of Src‐Tks5 signaling in invadopodia development, matrix‐remodeling activity, motility, and invasion.RESULTSOur studies demonstrated that Src was activated and Tks5 upregulated in high Gleason score prostate tumor specimens and in invasive prostate cancer cell lines. Remarkably, overexpression of Tks5 in LNCaP cells was sufficient to induce invadopodia formation and associated matrix degradation. This Tks5‐dependent increase in invasive behavior further depended on Src tyrosine kinase activity and the phosphorylation of Tks5 at tyrosine residues 557 and 619. In PC‐3 cells we demonstrated that Tks5 phosphorylation at these sites was necessary and sufficient for invadopodia‐associated matrix degradation and invasion.CONCLUSIONSOur results suggest a general role for Src‐Tks5 signaling in prostate tumor progression and the utility of Tks5 as a marker protein for the staging of this disease. Prostate 74:134–148, 2014. © 2013 Wiley Periodicals, Inc.
Princeton_TIGRESS: Protein geometry refinement using simulations and support vector machines
Authors: Khoury George A. , Tamamis Phanourios , Pinnaduwage Neesha , Smadbeck James , Kieslich Chris A. , Floudas Christodoulos A. 
Published: October 2013

ABSTRACTProtein structure refinement aims to perform a set of operations given a predicted structure to improve model quality and accuracy with respect to the native in a blind fashion. Despite the numerous computational approaches to the protein refinement problem reported in the previous three CASPs, an overwhelming majority of methods degrade models rather than improve them. We initially developed a method tested using blind predictions during CASP10 which was officially ranked in 5th place among all methods in the refinement category. Here, we present Princeton_TIGRESS, which when benchmarked on all CASP 7,8,9, and 10 refinement targets, simultaneously increased GDT_TS 76% of the time with an average improvement of 0.83 GDT_TS points per structure. The method was additionally benchmarked on models produced by top performing three‐dimensional structure prediction servers during CASP10. The robustness of the Princeton_TIGRESS protocol was also tested for different random seeds. We make the Princeton_TIGRESS refinement protocol freely available as a web server at http://atlas.princeton.edu/refinement. Using this protocol, one can consistently refine a prediction to help bridge the gap between a predicted structure and the actual native structure. Proteins 2014; 82:794–814. © 2013 Wiley Periodicals, Inc.
Elucidating the sequence of intact bioactive peptides by using electron capture dissociation and hot electron capture dissociation in a linear radio‐frequency quadrupole ion trap
Authors: Satake Hiroyuki , Manri Naomi , Kaneko Akihito , Hirabayashi Atsumu , Hasegawa Hideki , Hashimoto Yuichiro , Baba Takashi , Sakamoto Takeshi , Masuda Katsuyoshi 
Published: October 2013

RATIONALEElectron capture dissociation (ECD) is useful tool for sequencing of peptides and proteins with post‐translational modifications. To increase the sequence coverage for peptides and proteins, it is important to develop ECD device with high fragmentation efficiency.METHODSSequence analysis of intact undigested bioactive peptides (3000–5000 Da) was performed by use of electron capture dissociation (rf‐ECD) and collision‐induced dissociation (CID) in a linear radio‐frequency quadrupole ion trap that was coupled to a time‐of‐flight mass spectrometer. We applied rf‐ECD, hot rf‐ECD (rf‐ECD with high electron energy), and CID for intact bioactive peptide ions of various charge states and evaluated the sequence coverage of their fragment spectra.RESULTSHot rf‐ECD produced a higher number of c‐ and z‐type fragment ions of modified peptide ions as electron energy increased in lower charged peptide ions, and sequence coverage greater than 80% was obtained compared with the CID case (40–80%).CONCLUSIONSThe result indicates that intact bioactive modified peptides (Ghrelin, ANP) were correctly identified by use of hot rf‐ECD. Copyright © 2013 John Wiley & Sons, Ltd.
Age‐related motor dysfunction and neuropathology in a transgenic mouse model of multiple system atrophy
Authors: Fernagut P.O. , Meissner W.G. , Biran M. , Fantin M. , Bassil F. , Franconi J.M. , Tison F. 
Published: October 2013

ABSTRACTMultiple system atrophy (MSA) is a neurodegenerative disorder characterized by a progressive degeneration of the striatonigral, olivo‐ponto‐cerebellar, and autonomic systems. Glial cytoplasmic inclusions (GCIs) containing alpha‐synuclein represent the hallmark of MSA and are recapitulated in mice expressing alpha‐synuclein in oligodendrocytes. To assess if oligodendroglial expression of human wild‐type alpha‐synuclein in mice (proteolipid promoter, PLP‐SYN) could be associated with age‐related deficits, PLP‐SYN and wild‐type mice were assessed for motor function, brain morphometry, striatal levels of dopamine and metabolites, dopaminergic loss, and distribution of GCIs. PLP‐SYN displayed age‐related impairments on a beam‐traversing task. MRI revealed a significantly smaller brain volume in PLP‐SYN mice at 12 months, which further decreased at 18 months together with increased volume of ventricles and cortical atrophy. The distribution of GCIs was reminiscent of MSA with a high burden in the basal ganglia. Mild dopaminergic cell loss was associated with decreased dopamine turnover at 18 months. These data indicate that PLP‐SYN mice may recapitulate some of the progressive features of MSA and deliver endpoints for the evaluation of therapeutic strategies. Synapse 68:98–106, 2014. © 2013 Wiley Periodicals, Inc.
Regional brain imaging of vesicular acetylcholine transporter using o‐[125I]iodo‐trans‐decalinvesamicol as a new potential imaging probe
Authors: Kozaka Takashi , Uno Izumi , Kitamura Yoji , Miwa Daisuke , Anwar‐Ul Azim Mohammad , Ogawa Kazuma , Shiba Kazuhiro 
Published: October 2013

ABSTRACTIn this study, the regional rat brain distribution of radioiodinated o‐iodo‐trans‐decalinvesamicol ([125I]OIDV) was determined in vivo to evaluate its potential as a single‐photon emission computed tomography (SPECT) imaging probe for vesicular acetylcholine transporter (VAChT). Following intravenous injection, [125I]OIDV passed freely across the blood–brain barrier and accumulated in rat brain. The accumulation of [125I]OIDV in rat brain was significantly reduced by coadministration of (+/−)‐vesamicol (0.125 µmol). In contrast, the coadministration of σ‐receptor ligands, such as (+)‐pentazocine (0.125 µmol) as a σ‐1 receptor ligand and (+)−3‐(3‐hydroxyphenyl)‐N‐propylpiperidine (0.125 µmol) as a σ‐1 and σ‐2 receptor ligands, barely affected the accumulation of [125I]OIDV in rat brain. These findings in vivo were corroborated by autoradiographic analysis ex vivo. The authors found that the tracer binds with pharmacological selectivity to VAChT in rat brain and predicted that it may likewise serve in translational SPECT imaging studies of this marker in the integrity of cholinergic innervations. Synapse 68:107–113, 2014. © 2013 Wiley Periodicals, Inc.
Flow Disruptions During Trauma Care
Authors: Shouhed Daniel , Blocker Renaldo , Gangi Alex , Ley Eric , Blaha Jennifer , Margulies Daniel , Wiegmann Douglas A. , Starnes Ben , Karl Cathy , Karl Richard , Gewertz Bruce L. , Catchpole Ken R. 
Published: October 2013

AbstractBackgroundFlow disruptions (FDs) are deviations from the progression of care that compromise safety or efficiency. The frequency and specific causes of FDs remain poorly documented in trauma care. We undertook this study to identify and quantify the rate of FDs during various phases of trauma care.MethodsSeven trained observers studied a Level I trauma center over 2 months. Observers recorded details on FDs using a validated Tablet‐PC data collection tool during various phases of care—trauma bay, imaging, operating room (OR)—and recorded work‐system variables including breakdowns in communication and coordination, environmental distractions, equipment issues, and patient factors.ResultsResearchers observed 86 trauma cases including 72 low‐level and 14 high‐level activations. Altogether, 1,759 FDs were recorded (20.4/case). High‐level trauma comprised a significantly higher number (p = 0.0003) and rate of FDs (p = 0.0158) than low‐level trauma. Across the three phases of trauma care, there was a significant effect on FD number (p < 0.0001) and FD rate (p = 0.0005), with the highest in the OR, followed by computed tomography. The highest rates of FD per case and per hour were related to breakdowns in coordination.ConclusionsThis study is the largest direct observational study of the trauma process conducted to date. Complexities associated with the critical patient who arrives in the trauma bay lead to a high prevalence of disruptions related to breakdowns in coordination, communication, equipment issues, and environmental factors. Prospective observation allows individual hospitals to identify and analyze these systemic deficiencies. Appropriate interventions can then be evaluated to streamline the care provided to trauma patients.
Influence of Intraoperative Radiotherapy (IORT) on Perioperative Outcome after Surgical Resection of Rectal Cancer
Authors: Klink Christian Daniel , Binnebösel M. , Holy R. , Neumann U. P. , Junge K. 
Published: October 2013

AbstractBackgroundIntraoperative radiotherapy (IORT) for locally advanced or recurrent rectal cancer as an integral part of multimodal treatment might be an option to reduce local cancer recurrence. The aim of the present study was to determine the influence of IORT on the postoperative outcome and complications rates in the treatment of patients with adenocarcinoma of the rectum in comparison to patients with rectum resection only.MethodsA total of 162 patients underwent operation for International Union against Cancer stage III/IV rectal cancer or recurrent rectal cancer at our surgical department between 2004 and 2012. They were divided into two groups depending on whether they received IORT or not. General patient details, tumor, and operation details, as well as perioperative major and minor complications, were registered and compared.ResultsOf the 162 patients treated for stage III/IV rectal cancer, 52 underwent rectal resection followed by IORT. Complication rates were similar in the two groups. Operative time was significantly longer in the IORT group (248 ± 84 vs 177 ± 68 min; p < 0.001). No significant differences were found concerning anastomotic leakage rate, hospital stay, or wound infection rate.ConclusionsIntraoperative radiotherapy appears to be a safe treatment option in patients with locally advanced or recurrent rectal cancer with acceptable complication rates. The effect on local recurrence rate has to be estimated in long‐term follow‐up.
Perioperative Immunonutrition in Surgical Cancer Patients: A Summary of a Decade of Research
Authors: Klek Stanislaw , Szybinski Piotr , Szczepanek Kinga 
Published: October 2013

AbstractBackgroundImmunonutrition is assumed to enhance immune system function. In surgical patients, it is supposed to reduce postoperative complications. However, results of recent clinical trials have been puzzling and have not supported this theory.AimThe aim of our study was to evaluate the value of enteral and parenteral postoperative immunonutrition.MethodsAfter initial evaluation of 969 patients, the intent‐to‐treat analysis included 776 patients (female 407, male 466, mean age 61.1 years) undergoing gastric or pancreatic resections between 2001 and 2009. All patients were randomly assigned after surgery to one of the following groups: standard enteral nutrition (SEN), immunomodulating enteral nutrition (IMEN), standard parenteral nutrition (SPN), or immunomodulating parenteral nutrition (IMPN). All malnourished patients received preoperative parenteral nutrition. Number and type of postoperative complications, length of hospitalization (length of stay [LOS]), and vital organ function were assessed.ResultsNo statistically significant differences were observed in well‐nourished patients, during either enteral or parenteral intervention, independent of the type of intervention (standard or immunomodulating). However, analysis of the malnourished group revealed the positive impact of enteral immunonutrition on reduction of postoperative complications (28.3 vs. 39.2 %, respectively; p = 0.043) and LOS (17.1 and 13.1 days, respectively; p < 0.05) compared with a standard enteral diet. The cross‐analysis of SEN, IMEN, SPN, and IMPN was insignificant.ConclusionsThe type of postoperative nutrition was of no importance in well‐nourished patients. However, in malnourished patients, enteral immunonutrition helped to improve treatment outcome. These findings suggest its use as a method of choice during the postoperative period.
Wheat–barley hybridization: the last 40 years
Authors: Molnár-Láng Márta , Linc Gabriella , Szakács Éva 
Published: October 2013

AbstractSeveral useful alien gene transfers have been reported from related species into wheat (Triticum aestivum), but very few publications have dealt with the development of wheat/barley (Hordeum vulgare) introgression lines. An overview is given here of wheat × barley hybridization over the last forty years, including the development of wheat × barley hybrids, and of addition and translocation lines with various barley cultivars. A short summary is also given of the wheat × barley hybrids produced with other Hordeum species. The meiotic pairing behaviour of wheat × barley hybrids is presented, with special regard to the detection of wheat–barley homoeologous pairing using the molecular cytogenetic technique GISH. The effect of in vitro multiplication on the genome composition of intergeneric hybrids is discussed, and the production and characterization of the latest wheat/barley translocation lines are presented. An overview of the agronomical traits (β-glucan content, earliness, salt tolerance, sprouting resistance, etc.) of the newly developed introgression lines is given. The exploitation and possible use of wheat/barley introgression lines for the most up-to-date molecular genetic studies (transcriptome analysis, sequencing of flow-sorted chromosomes) are also discussed.
Classifying Married Adults Diagnosed With Alpha‐1 Antitrypsin Deficiency Based on Spousal Communication Patterns Using Latent Class Analysis: Insights for Intervention
Authors: Smith Rachel A. , Wienke Sara E. , Baker Michelle K. 
Published: October 2013

AbstractMarried adults are increasingly exposed to test results that indicate an increased genetic risk for adult‐onset conditions. For example, a SERPINA1 mutation, associated with alpha‐1 antitrypsin deficiency (AATD), predisposes affected individuals to diseases such as chronic obstructive pulmonary disease (COPD) and cancer, which are often detected in adulthood. Married adults are likely to discuss genetic test results with their spouses, and interpersonal research suggests that spouses’ communication patterns differ. Latent class analysis was used to identify subgroups of spousal communication patterns about AATD results from a sample of married adults in the Alpha‐1 Research Registry (N = 130). A five‐class model was identified, and the subgroups were consistent with existing spousal‐communication typologies. This study also showed that genetic beliefs (e.g., genetic stigma), emotions, and experiences (e.g., insurance difficulties) covaried with membership in particular subgroups. Understanding these differences can serve as the foundation for the creation of effective, targeted communications interventions to address the specific needs and conversational patterns of different kinds of couples.
Renal Cyclooxygenase Products are Higher and Lipoxygenase Products are Lower in Early Disease in the pcy Mouse Model of Adolescent Nephronophthisis
Authors: Yamaguchi Tamio , Lysecki Clara , Reid Ashleigh , Nagao Shizuko , Aukema Harold M. 
Published: October 2013

AbstractNephronophthisis (NPHP) is a pediatric form of hereditary polycystic kidney disease (PKD), and is the leading cause of end stage renal disease in children. The pcy mouse is an orthologous model of human NPHP, with a mutation in the Nphp3 gene. Renal phospholipase A2, cyclooxygenase (COX) 1 and cyclic AMP are elevated in this model, suggesting that eicosanoid formation may be altered. In another type of PKD observed in the Han:SPRD‐Cy rat, inhibition of eicosanoid production slows disease progression. If renal eicosanoids are similarly altered in NPHP, potential for pharmacologic intervention also may exist for this disorder. Therefore, renal fatty acids and eicosanoids were determined in pcy and normal mice at 15, 30 and 60 days of age by gas chromatography and HPLC–tandem mass spectrometry, respectively. Renal cysts in enlarged kidneys were observed in pcy mice by 15 days of age and increased over time. Renal phospholipid ARA levels were higher in pcy compared to normal mice at 15 and 30 days. Eicosanoid differences were observed starting at 30 days, when the COX products 6‐keto‐prostaglandin (PG) F1α, thromboxane B2 and PGE2 were higher in pcy compared to normal kidneys. Overall, total COX products were elevated at 30 and 60 days. In contrast, the levels of the lipoxygenase (LOX) products were not altered until 60 days of age and these were lower in pcy kidneys compared to normal. These findings suggest that altered eicosanoids play a role in NPHP, and that manipulating these levels with pharmacologic agents may have therapeutic potential.
Genetisches Modell der autosomal-rezessiv erblichen proximalen spinalen Muskelatrophie
Authors: Langer S. , Rudnik-Schöneborn S. , Zerres K. , Grimm T. 
Published: October 2013

ZusammenfassungDie proximale infantile und juvenile spinale Muskelatrophie (SMA) ist eine der häufigsten autosomal-rezessive Erbkrankheiten. Man unterteilt die Patienten in 3 Gruppen, SMA Typ I-III, abhängig von der Schwere der Erkrankung (den erreichten Meilensteinen). Das hauptsächlich verantwortliche Gen, das Survival-motor-neuron(SMN1)-Gen, ist auf Chromosom 5 lokalisiert. Während das Normalallel meist mit einer oder 2SMN1-Kopien vorliegt, sind die Defektallele bei den meisten Patienten von einer Deletion betroffen; bei einigen liegen Punktmutationen vor. Bei den Deletionen wiederum unterscheidet man zwischen einfacher und großer Deletion, die über dasSMN1-Gen hinausgeht. Ein homozygotes Auftreten letzterer führt zu pränataler Letalität.Für die vorliegende Arbeit wurden zahlreiche in der Literatur verfügbare Daten zur SMA Typ I-III zusammengetragen und in ihrer Abhängigkeit in einem genetischen Modell zusammengefasst. So war es möglich, fehlende Parameter zu schätzen, um genauere Aussagen über Genotypen machen zu können. Die einzelnen Allelfrequenzen konnten wie folgt geschätzt werden:Normalallel b (1 SMN1-Kopie): ≈ 0,9527; Normalallel c (2 SMN1-Kopien): ≈ 0,0362; einfache Deletion a (0 SMN1-Kopien): ≈ 0,0104; Punktmutation d (1 SMN1-Kopie): ≈ 0,0003; große Deletion g (0 SMN1-Kopien): ≈ 0,0004. Die Genhäufigkeit beträgt etwa 1:90 mit einer Heterozygtenfrequenz von 1:46.
Schwangerschaftsverlauf und geburtshilfliche Risiken bei 178 Frauen mit hereditären neuromuskulären Erkrankungen
Authors: Awater C. , Zerres K. , Rudnik-Schöneborn S. 
Published: October 2013

Zusammenfassung

Hintergrund
Informationen zu Schwangerschaft und Entbindung bei Frauen mit hereditären neuromuskulären Erkrankungen (NMD) sind aufgrund der Seltenheit meist auf kleine Fallserien und Kasuistiken beschränkt.

Ziel der Arbeit
Die Frage, ob erhöhte geburtshilfliche Risiken und eine mögliche Beeinflussung des Krankheitsverlaufes bestehen, ist auch für die genetische Beratung von großer Bedeutung und soll in der vorliegenden Studie untersucht werden.

Methode
Die Schwangerschaftsverläufe von Frauen mit myotoner Dystrophie Typ 1 (DM1) und Typ 2 (DM2), Charcot-Marie-Tooth-Neuropathie (CMT), proximaler spinaler Muskelatrophie (SMA), Gliedergürtelmuskeldystrophie (LGMD), fazioskapulohumeraler Muskeldystrophie (FSHD) und kongenitaler Myopathie (CM) wurden retrospektiv untersucht. Es wurden 380 Schwangerschaften mit 315 Neugeborenen von 178 Patientinnen dokumentiert.

Ergebnisse und Schlussfolgerung
Die Fehlgeburtenrate war im Normbereich. Frühgeburten, vaginale Operation und Kaiserschnitte stellten v. a. bei DM1 und SMA wichtige Komplikationen dar, während fetale Lageanomalien gehäuft bei DM1, LGMD und rollstuhlpflichtigen Patientinnen auftraten. Abgesehen von DM1-Geburten mit kongenitaler Form war der Gesundheitszustand der Neugeborenen gut. Eine erhebliche Verschlechterung während der Schwangerschaft gaben insbesondere Frauen mit LGMD an.
Prolonged maternal separation disturbs the serotonergic system during early brain development
Authors: Ohta Ken‐ichi , Miki Takanori , Warita Katsuhiko , Suzuki Shingo , Kusaka Takashi , Yakura Tomiko , Liu Jun‐Qian , Tamai Motoki , Takeuchi Yoshiki 
Published: October 2013

AbstractEarly life stress interrupts brain development through the disturbance of various neurotransmitter and neurotrophic factor activities, but the details remain unclear. In the current study, we focused on the serotonergic system, which plays a critical role in brain development, and examined the time‐dependent influence of prolonged maternal separation on male Sprague‐Dawley rats. The rats were separated from their dams for 3 h twice‐daily during postnatal days (PDs) 2–20. The influence of prolonged maternal separation was analyzed on PDs 7, 14, 21, and 28 using HPLC to assess concentrations of serotonin and 5‐hydroxyindoleacetic acid and using real‐time RT‐PCR to measure mRNA expression of the serotonin 1A and 2A receptors in various brain regions. HPLC revealed imbalance between serotonin and 5‐hydroxyindoleacetic acid in midbrain raphe nuclei, the amygdala, the hippocampus, and the medial prefrontal cortex (mPFC) on PDs 7 and 14. Furthermore, real‐time RT‐PCR showed attenuation of mRNA expression of the serotonin 1A receptor in the hippocampus and the mPFC and of the serotonin 2A receptor only in the mPFC on PDs 7 and 14. The observed alterations returned to control levels after maternal separation ended. These findings suggest that the early life stress of prolonged maternal separation disturbs the serotonergic system during a crucial period of brain development, which might in part be responsible for emotional abnormalities later in life.
EVIDENCE OF EVIDENCE IS EVIDENCE UNDER SCREENING-OFF
Authors: Roche William 
Published: October 2013

AbstractAn important question in the current debate on the epistemic significance of peer disagreement is whether evidence of evidence is evidence. Fitelson argues (persuasively in my view) that, at least on some renderings of the thesis that evidence of evidence is evidence, there are cases where evidence of evidence isnotevidence. I introduce a ‘screening-off’ condition and show that under this condition evidence of evidenceisevidence.