bluuebunny/crossref_metadata_2025 huggingface dataset:
Isolation and Clonal Assay of Adult Lung Epithelial Stem/Progenitor Cells
Authors: Bertoncello Ivan , McQualter Jonathan
Published: January 2011

Adult mouse lung epithelial stem/progenitor cells (EpiSPC) can be defined in vitro as epithelial colony‐forming units that are capable of self‐renewal, and which when co‐cultured with lung mesenchymal stromal cells (MSC) are able to give rise to differentiated progeny comprising mature lung epithelial cells. This unit describes a protocol for the prospective isolation and in vitro propagation and differentiation of adult mouse lung EpiSPC. The strategy used for selection of EpiSPC and MSC from adult mouse lung by enzymatic digestion and flow cytometry is based on the differential expression of CD45, CD31, Sca‐1, EpCAM, and CD24. The culture conditions required for the differentiation (co‐culture with MSC) and expansion (stromal‐free culture with FGF‐10 and HGF) of EpiSPC are described. Curr. Protoc. Stem Cell Biol. 16:2G.1.1‐2G.1.12. © 2011 by John Wiley & Sons, Inc.
Digit ratio (2D:4D) and rowing ergometer performance in males and females
Authors: Longman D. , Stock J.T. , Wells J.C.K.
Published: January 2011

Fetal and adult testosterone may be vital in the establishment and maintenance of sex‐dependent abilities associated with male physical competitiveness. It has been shown that digit ratio (2D:4D) is negatively associated with prenatal testosterone, and it is also negatively associated with ability in sports such as football, skiing, middle distance running, and endurance running, which are dependent upon an efficient cardiovascular system. The relationship between digit ratio and sports requiring high power (physical strength) output in addition to well‐developed cardiovascular systems has not been defined. This study investigated this association in male and female young adult rowers. Participants (77 male and 70 female) were student rowers encompassing a range of abilities from the University of Cambridge. Bilateral digit measurements were taken blind from each subject using Mitutoyo vernier calipers. Rowing performance over 2,000 m was assessed using the Concept 2 rowing ergometer. Significant negative correlations were observed between 2,000 m ergometer performance and male digit ratios, which persisted following adjustment for rowing experience and height. However, no such significant association was found in females despite a comparable sample size. Our data indicate that digit ratio is a predictor of ability in rowing, a sport which requires both cardiovascular efficiency and high power output, in males but not females. This in turn suggests that fetal testosterone exposure has long‐term effects on traits associated with physical power in males but not females, suggesting a sex‐difference in the capacity to respond to such exposures. Am J Phys Anthropol, 2011. © 2011 Wiley‐Liss, Inc.
The Narrow Niche hypothesis: Gray squirrels shed new light on primate origins
Authors: Orkin Joseph D. , Pontzer Herman
Published: January 2011

Current hypotheses for primate origins propose that nails and primate‐like grasping hands and feet were important early adaptations for feeding in fine branches. Comparative research in this area has focused on instances of convergence in extant animals, showing that species with primate‐like morphology feed predominantly from terminal branches. Little has been done to test whether animals without primate‐like morphology engage in similar behavior. We tested the fine‐branch niche hypothesis for primate origins by observing branch use in Eastern gray squirrels, Sciurus carolinensis, a species lacking primate grasping adaptations that has been understudied in the context of primate origins. We hypothesized that because gray squirrels lack primate‐like grasping adaptations, they would avoid feeding and foraging in terminal branches. Instantaneous focal animal sampling was used to examine the locomotor and postural behaviors used while feeding and foraging. Our results demonstrate habitual and effective usage of terminal branches by gray squirrels while feeding and foraging, primarily on tree seeds (e.g., oak, maple, and elm). Discriminant function analysis indicates that gray squirrels feed and forage like primates, unlike some other tree squirrel species. Given the absence of primate‐like features in gray squirrels, we suggest that although selection for fine‐branch foraging may be a necessary condition for primate origins, it is not sufficient. We propose an alternative model of primate origins. The Narrow Niche hypothesis suggests that the primate morphological suite evolved not only from selection pressure for fine branch use, but also from a lack of engagement in other activities. Am J Phys Anthropol, 2011. © 2011 Wiley‐Liss, Inc.
Brief communication: Y‐chromosome haplogroup analysis indicates that Chinese Tuvans share distinctive affinity with Siberian Tuvans
Authors: Chen Zheng , Zhang Yongke , Fan An , Zhang Yanan , Wu Yanping , Zhao Qianjun , Zhou Yong , Zhou Canlin , Bawudong M. , Mao Xinmin , Ma Yuehui , Yang Lingyun , Ding Yuanling , Wang Xueqin , Rao Shaoqi
Published: January 2011

Tuvans are mainly distributed in Siberia (the Republic of Tuva), Mongolia, and China. The genetic origin of Chinese Tuvans remains controversial. The Tuvans in China were classified as Mongolians in the early 1950s by the National Ethnic Affairs Commission of China, but they defined themselves as a separate group. To resolve this dispute and determine their genetic relationships with the peoples in Central Asia, we randomly selected 150 male subjects from the Tuvans in the Altai region of Xinjiang Uygur Autonomous Region in China. Fourteen Y chromosomal markers were genotyped using the RFLP method or direct sequencing. These haplogroup data were combined with public data for 15 populations in South Siberia and Central Asia. Tuvans in both China and the Republic of Tuva had the highest frequencies of haplogroups K‐M9 and Q‐M242. Principal component analysis demonstrated that the Tuvans in China were of a distinct cluster, separated from their neighbors, the Mongolians and Kazakhs, which finding was consistent with the Analysis of Molecular Variances. Further population tree analysis revealed that Tuvans were on a far‐separated cluster from their neighbors. Based on these results, we propose that the Tuvans (in both China and the Republic of Tuva) constitute a group distinct from Mongolians and from other Central Asia populations. However, the genetic results might be the consequence of some evolutionary forces like genetic drift and founder effect, and do not necessarily reflect their ultimate origin. Am J Phys Anthropol, 2011. © 2011 Wiley‐Liss, Inc.
Genetic structure of the paternal lineage of the Roma People
Authors: Pamjav Horolma , Zalán Andrea , Béres Judit , Nagy Melinda , Chang Yuet Meng
Published: January 2011

According to written sources, Roma (Romanies, Gypsies) arrived in the Balkans around 1,000 years ago from India and have subsequently spread through several parts of Europe. Genetic data, particularly from the Y chromosome, have supported this model, and can potentially refine it. We now provide an analysis of Y‐chromosomal markers from five Roma and two non‐Roma populations (N = 787) in order to investigate the genetic relatedness of the Roma population groups to one another, and to gain further understanding of their likely Indian origins, the genetic contribution of non‐Roma males to the Roma populations, and the early history of their splits and migrations in Europe. The two main sources of the Roma paternal gene pool were identified as South Asian and European. The reduced diversity and expansion of H1a‐M82 lineages in all Roma groups imply shared descent from a single paternal ancestor in the Indian subcontinent. The Roma paternal gene pool also contains a specific subset of E1b1b1a‐M78 and J2a2‐M67 lineages, implying admixture during early settlement in the Balkans and the subsequent influx into the Carpathian Basin. Additional admixture, evident in the low and moderate frequencies of typical European haplogroups I1‐M253, I2a‐P37.2, I2b‐M223, R1b1‐P25, and R1a1‐M198, has occurred in a more population‐specific manner. Am J Phys Anthropol, 2011. © 2011 Wiley‐Liss, Inc.
Periodontal disease in a Portuguese identified skeletal sample from the late nineteenth and early Twentieth Centuries
Authors: Wasterlain Sofia N. , Cunha Eugénia , Hillson Simon
Published: January 2011

Periodontal status was investigated in 600 adult dentitions belonging to the identified osteological collections curated at the University of Coimbra, Portugal. These collections date to a point temporally intermediate between the large epidemiological studies of the 20th century and archaeological collections that antedate the 19th century. The aim of this study is to compare periodontal data derived from contemporary samples with statistics compiled from epidemiological studies to determine if factors such as age‐at‐death, sex, and tooth type are essential or not to account for in future archaeological studies of periodontitis. Periodontal disease status was assessed based on the textural and architectural variations of the interdental septum and the extent of bone loss. Overall, the frequency of periodontitis within the Coimbra collections is 73.8%. Men were more susceptible to periodontal disease than women. Gingivitis was widespread in the younger age groups. Destructive periodontitis was observed early in adulthood, rising steadily with age. The most susceptible sites to periodontal breakdown were located in the posterior region of the upper jaw. Some variation in reported frequencies of periodontitis was found in epidemiological reports, which might result from variation in methods for identifying the pathology, differences in the age composition of the samples examined, variation in oral hygiene and/or diet, or some other factors. Regarding the pattern of distribution of periodontal disease, Coimbra results were similar to comparable modern epidemiological surveys, making clear the importance of considering sex, age, and oral distribution of periodontitis in future archaeological studies. Am J Phys Anthropol, 2011. © 2011 Wiley‐Liss, Inc.
Challenging views on the peopling history of East Asia: The story according to HLA markers
Authors: Di Da , Sanchez‐Mazas Alicia
Published: January 2011

The peopling of East Asia by the first modern humans is strongly debated from a genetic point of view. A north‐south genetic differentiation observed in this geographic area suggests different hypotheses on the origin of Northern East Asian (NEA) and Southern East Asian (SEA) populations. In this study, the highly polymorphic HLA markers were used to investigate East Asian genetic diversity. Our database covers a total of about 127,000 individuals belonging to 84 distinct Asian populations tested for HLA‐A, ‐B, ‐C, ‐DPB1, and/or ‐DRB1 alleles. Many Chinese populations are represented, which have been sampled in the last 30 years but rarely taken into account in international research due to their data published in Chinese. By using different statistical methods, we found a significant correlation between genetics and geography and relevant genetic clines in East Asia. Additionally, HLA alleles appear to be unevenly distributed: some alleles observed in NEA populations are widespread at the global level, while some alleles observed in SEA populations are virtually unique in Asia. The HLA genetic variation in East Asia is also characterized by a decrease of diversity from north to south, although a reverse pattern appears when one only focuses on alleles restricted to Asia. These results reflect a more complex migration history than that illustrated by the “southern‐origin” hypothesis, as genetic contribution of ancient human migrations through a northern route has probably been quite substantial. We thus suggest a new overlapping model where northward and southward opposite migrations occurring at different periods overlapped. Am J Phys Anthropol, 2011. © 2011 Wiley‐Liss, Inc.
Ring‐opening polymerization of trimethylenecarbonate by the bridged diphenoxo ytterbium (II) complex
Authors: Zhao B. , Hu X. L. , Lu C. R.
Published: January 2011

A novel ytterbium (II) complex 2 supporting by a bridged bisphenolate ligand H2LOC4H7 (L = C4H7OCH2N(CH2‐2‐OC6H2‐3,5‐Bu)2) with a tetrahydrofuran donor on side‐arm was synthesized in high yield and characterized by elementary analysis, IR, 1H‐NMR, and 13C‐NMR. Ring‐opening polymerization of 1,3‐trimethylenecarbonate (TMC) was carried out using complex 2 and a known complex [Me2NCH2CH2N(CH2‐2‐O‐3,5‐C6H2(But)2)2]Yb 1 as the initiators, respectively. It was found that both complexes 1 and 2 can alone initiate the ring‐opening polymerization of TMC, and complex 1 showed higher activity than complex 2. The activity of both complexes 1 and 2 was found to be higher than that of monodentate phenoxo ytterbium (II) complex (2,6‐Bu‐C6H3O)2Yb(THF)3. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2011
Quantitative Three‐Dimensional Analysis of Embryonic Chick Morphogenesis Via Microcomputed Tomography
Authors: Kim Jun Sup , Min Jouha , Recknagel Andrew K. , Riccio Mark , Butcher Jonathan T.
Published: January 2011

Micro‐computed tomographic imaging of a stage HH36 chick embryo. Signal intensity was pseudocolored to identify skeletal, vascular, and soft tissue components. See Kim et al., on page 1, in this issue.
In Situ Raman and Pulse Reaction Study on the Partial Oxidation of Methane to Synthesis Gas over a Pt/Al2O3 Catalyst
Authors: Wang Mei‐Liu , Zheng Hao‐Zhuan , Li Jian‐Mei , Weng Wei‐Zheng , Xia Wen‐Sheng , Huang Chuan‐Jing , Wan Hui‐Lin
Published: January 2011

Catalytic partial oxidation of methane (POM) to synthesis gas (syngas) over Pt/Al2O3 was investigated by in situ microprobe Raman and pulse reaction methods with attention focused on the mechanism of syngas formation in the oxidation zone (i.e., the catalyst zone in which O2 was still available in the reaction feed). It was found that the amount of platinum oxide in the catalyst under POM conditions was below the detection level of Raman spectroscopy. Raman bands of carbon species that originated from methane dissociation were detected at the entrance of the catalyst bed under working conditions. The results of the pulse reaction study on POM as well as steam and CO2 reforming of methane at 700 °C with a contact time of less than 1 ms over the catalyst suggest that pyrolysis of methane on reduced platinum sites followed by coupling of two surface hydrogen atoms to H2 and partial oxidation of surface carbon species to CO are the major reactions responsible for syngas formation in the oxidation zone. Under the experimental conditions, steam and CO2 reforming of methane play only a minor role in syngas formation in the same reaction zone. The contribution of the last two reactions increases with increasing contact time.
Facile One‐Step Catalytic Grafting of N‐Hydroxysuccinimidyl‐Ester‐Functionalized Methallylsilane onto Silica for Enzyme Immobilization
Authors: Jung Un‐Young , Park Jung‐Woo , Han Eun‐Hee , Kang Sin‐Gun , Lee Sera , Jun Chul‐Ho
Published: January 2011

A one‐step grafting method of NHS‐ester group is described for the immobilization of enzymes onto a silica surface at room temperature. Pure NHS‐ester functionalized methallylsilane was prepared as a grafting reagent and showed remarkable grafting efficiency with acid catalysts at room temperature. As a result, mesoporous silica balls bearing a covalently immobilized enzyme could be obtained with a high loading rate compared to conventional multistep grafting methods. This one‐step procedure offers the advantages of precise measurement of the high loading efficiency of the NHS‐ester group, and the exclusive formation of only the NHS‐ester group, which reduces the presence of unreacted functionalities.
Optical mapping of DNA: Single‐molecule‐based methods for mapping genomes
Authors: Neely Robert K. , Deen Jochem , Hofkens Johan
Published: January 2011

The technologies associated with DNA sequencing are rapidly evolving. Indeed, single‐molecule DNA sequencing strategies are cheaper and faster than ever before. Despite this progress, every sequencing platform to date relies on reading the genome in small, abstract fragments, typically of less than 1000 bases in length. The overarching aim of the optical map is to complement the information derived from DNA sequencing by providing long‐range context on which these short sequence reads can be built. This is typically done using an enzyme to target and modify at short DNA sequences of, say, six bases in length throughout the genome. By accurately placing these short pieces of sequence on long genomic DNA fragments, up to several millions of bases in length, a scaffold for sequence assembly can be obtained. This review focuses on three enzymatic approaches to optical mapping. Optical mapping was first developed using restriction enzymes to sequence‐specifically cleave DNA that is immobilized on a surface. More recently, nicking enzymes have found application in the sequence‐specific fluorescent labeling of DNA for optical mapping. Such covalent modification allows the DNA to be imaged in solution, and this, in combination with developing nanofluidic technologies, is enabling new high‐throughput approaches to mapping. And, finally, this review will discuss the recent development of mapping with subdiffraction‐limit precision using methyltransferase enzymes to label the DNA with an ultrahigh density. © 2011 Wiley Periodicals, Inc. Biopolymers 95: 298–311, 2011.
Neuronal Differentiation of C17.2 Neural Stem Cells Induced by a Natural Flavonoid, Baicalin
Authors: Li Ming , Tsang Kam‐Sze , Choi Sze‐Ting , Li Karen , Shaw Pang‐Chui , Lau Kwok‐Fai
Published: January 2011

Natural medicinal materials are a significant resource for the identification of compounds with specific biological properties. In this study, we employed multipotent C17.2 neural stem cells as a model for screening natural compounds that possess neural differentiation‐inducing properties. We show here for the first time that, out of the 67 compounds tested, the flavonoid baicalin is a potent differentiation‐inducing agent. Baicalin increased the number of cells bearing extended neurites and the expression levels of a number of neuronal markers. Importantly, baicalin promoted the expression of several key neurogenic transcriptional factors. Moreover, we demonstrated that baicalin enhanced the phosphorylation/activation of Erk1/2. Inhibition of Erk1/2 activation by the MEK inhibitor U0126 attenuated the neuronal differentiation‐inducing effect of baicalin. Taken together, our findings suggest that baicalin induces neuronal differentiation of C17.2 neural stem cells and that this is mediated by activation of Erk1/2. Our work lays the foundation for exploring baicalin for the promotion of neural regeneration after injury or disease.
Successful primary percutaneous coronary intervention in the first trimester of pregnancy
Authors: Babic Zdravko , Gabric Ivo Darko , Pintaric Hrvoje
Published: January 2011

A 28‐year‐old patient, medical nurse, in 10th week of her second pregnancy suffered ventricular fibrillation just after entering the waiting room of the emergency department. After she was successfully defibrillated, electrocardiography revealed a large acute anteroseptolateral ST elevation myocardial infarction. Urgent coronarography was done (premedication with 300 mg of aspirin and 600 mg of clopidogrel) with 90 min door‐to‐balloon time. Proximal left anterior descending occlusion was found, primary percutaneous coronary intervention was done using Amazonia CroCo 3.0/12 bare‐metal stent, and Thrombolysis in Myocardial Infarction III flow was achieved. During the procedure, the patient was wrapped in lead apron. Because of postresuscitational agitation, procedure was done in intravenous anesthesia. The revealed risk factors were smoking and hypercholesterolemia. PAI‐1 gene 4G/4G genotype and Apo E gene E2/E4 genotype were also found. Estimated X‐ray dosage that fetus received during the procedure was 0.45 mSv, which is less than the upper safe limit in pregnancy. All drugs given to our patient (clopidogrel, aspirin, ivabradine, bisoprolol, anesthetics, low‐molecular‐weight heparin, and unfractionated heparin) have B or C Food and Drug Administration Pregnancy Category. Fetal ultrasonography showed normal fetal growth, and, after consultation with our team, the patient decided to maintain the pregnancy. Before discharge echocardiography showed left ventricle of normal size with anteroseptolateral hypokinesia, small apical aneurysm, left ventricular ejection fraction of 40–45%, and diastolic dysfunction grade II, without pulmonary hypertension. At the 36th week of pregnancy, the patient was hospitalized and closely monitored; clopidogrel and aspirin were discontinued, and low‐molecular‐weight heparin was administered. She gave birth to a normal boy by vaginal delivery with epidural anesthesia and without any complication. © 2010 Wiley‐Liss, Inc.
Sustained long‐term benefit of patent foramen ovale closure on migraine
Authors: Trabattoni Daniela , Fabbiocchi Franco , Montorsi Piero , Galli Stefano , Teruzzi Giovanni , Grancini Luca , Gatto Pamela , Bartorelli Antonio L.
Published: January 2011

Objectives: This single‐center, observational, prospective study evaluated the impact of patent foramen ovale (PFO) closure on migraine attacks over time. Background: PFO closure may reduce the frequency and severity of migraine headaches in patients with significant right‐to‐left shunts. Methods: Between May 2000 and September 2009, 305 consecutive patients (mean age, 43 ± 12 years; 54.5% women) with a prior embolic cerebrovascular event underwent PFO closure with the Amplatzer PFO occluder for recurrence prevention. All patients had right‐to‐left shunts; the shunts were associated with migraine symptoms in 77 (25%), either alone (n = 64, 83%) or with aura (n = 13, 17%). Septal aneurysm was present in 15 (19.5%) migraine patients, and 43 (56%) had a previous transient brain ischemic attack. All migraine patients had a computed tomography scan or magnetic resonance imaging, indicating a previous brain ischemic lesion. All 305 patients underwent transthoracic echocardiography with clinical follow‐up at 24 hr, at 3, 6, and 12 months, and then yearly. Results: An acute migraine attack occurred 24–48 hr after PFO closure in 28 (36.4%) of 77 patients. There was a significant reduction (>50%) in the number and intensity of attacks in 46 (60.5%) of 77 patients at the 3‐month follow‐up. At the 12‐month follow‐up, migraine had ceased in 23 (46%) patients, and 20 (40%) had a reduction in the migraine recurrence rate and disabling symptoms. These results were maintained at follow‐up (mean, 28 ± 27 months). There was overall improvement in migraine in 89% of the treated patients. Conclusions: Percutaneous PFO closure in migraineurs may provide beneficial mid‐term and long‐term results, with significant reduction in the intensity and frequency of headache symptoms. © 2010 Wiley‐Liss, Inc.
Coronary obstruction following transcatheter aortic valve‐in‐valve implantation for failed surgical bioprostheses
Authors: Gurvitch Ronen , Cheung Anson , Bedogni Francesco , Webb John G.
Published: January 2011

Transcatheter aortic valve implantation (TAVI) for failed surgical bioprostheses, or “valve‐in‐valve” implantation, is a therapeutic option for high‐risk patients. While coronary occlusion during TAVI for native aortic stenosis has been described, in the setting of valve‐in‐valve implantation the bioprsthetic posts may be protective against this complication. We describe the first two cases of coronary occlusion following valve‐in‐valve therapy, both occurring during treatment of degenerated Mitroflow bioprostheses. Aortic root anatomy, coronary ostial position, and the specifics of the bioprosthetic valve type need to be considered in assessing and preventing this rare complication. © 2011 Wiley‐Liss, Inc.
Simultaneous hybrid revascularization by bilateral carotid stenting and coronary artery bypass grafting
Authors: Visconti Gabriella , Marino Luigi , Briguori Carlo
Published: January 2011

Management of patient with concomitant severe coronary and carotid artery disease is challenging. The combined or staged surgical revascularization is burdened by a high risk of morbidity and mortality. Carotid artery stenting (CAS) has been recently introduced as an alternative revascularization approach. We describe a case of simultaneous hybrid revascularization by CAS followed by immediate coronary artery bypass graft in a patient with a severe coronary artery disease and bilateral carotid artery stenosis. © 2013 Wiley Periodicals, Inc.
PFO and paradoxical embolism producing events other than stroke
Authors: Dao Catherine N. , Tobis Jonathan M.
Published: January 2011

Background: A patent foramen ovale (PFO) is a risk factor for cerebral events such as cryptogenic stroke, transient ischemic attacks, and migraine headaches. Far less commonly, PFO is associated with non‐cerebral, paradoxical systemic embolic events such as myocardial infarction (MI), renal infarct, and limb ischemia. This report details the incidence of systemic paradoxical emboli at our institution. Methods: 416 patients were referred for evaluation of PFO related conditions from 2001 to 2009. Clinical history and medical records of the patients were reviewed for incidence of cryptogenic stroke, transient ischemic attack (TIA), migraine headache, arterial desaturation, and noncerebral systemic embolism. Results: As the primary presenting symptom, 219 patients had a diagnosis of cryptogenic stroke, 38 patients had migraine headaches, and 80 patients had transient neurologic deficits consistent with a TIA or complex headache. Twelve patients (2.9% of the total population) presented with a presumptive diagnosis of systemic embolism. Eight of these patients had acute MI diagnosed by elevated cardiac biomarkers, electrocardiogram changes, and/or imaging evidence of a left ventricular wall motion abnormality, without evidence of obstructive coronary disease on angiography. Four patients had evidence of peripheral embolism to a systemic artery, including the popliteal artery, ophthalmic artery, and brachial artery. PFO closure was performed in 197 patients (47.4% of the total population), including eight patients in the systemic embolism group. All closure procedures were successful. Conclusion: Although most paradoxical emboli travel to the brain, noncerebral paradoxical embolism is also associated with PFO. In addition to embolism of thrombus, there may be paradoxical passage of vasoactive chemicals that induce intense coronary spasm and myocardial infarction. Diagnosis is often challenging, given the lack of definitive criteria and the need to exclude other potential etiologies. © 2011 Wiley‐Liss, Inc.
Radial access site inflammatory reaction to a recently available hydrophilic coated sheath
Authors: Swaminathan Rajesh V. , Wong S. Chiu
Published: January 2011

A sterile inflammatory reaction at the radial access site has been described in the literature as an adverse local reaction to Cook hydrophilic coated sheaths during transradial catheterization. To date, this reaction has not been observed with non‐Cook hydrophilic sheaths. Here, we describe two cases of such a reaction with Glidesheaths™ at our institution. © 2011 Wiley‐Liss, Inc.
Pulmonary perfusion scans following transcatheter patent ductus arteriosus closure using the Amplatzer devices
Authors: Kharouf Rami , Heitschmidt Mary , Hijazi Ziyad M.
Published: January 2011

Introduction: Obstruction to flow in the left pulmonary artery (LPA) is a well‐known complication after transcatheter device closure of patent ductus arteriosus (PDA). This complication has been studied for different devices using lung perfusion radionuclide scintigraphy (LPRS), but not for Amplatzer devices. This study was performed to evaluate the effect of such devices on lung perfusion using LPRS. Methods: This is a retrospective study that looked at all patients who had PDA closure using different Amplatzer devices at our center between July 1999 and January 2007. All patients underwent LPRS within 24 hr of the procedure. We compared LPRS with other hemodynamic data obtained by cardiac catheterization and echocardiography. Results are presented as mean ± SD or median and ranges. Results: A total of 70 patients had PDA closure using an Amplatzer device; median age was 1.8 years (4 months to 75 years) and median weight was 12 kg (5–112 Kg). Nine patients had associated cardiac anomalies. Sixty eight patients had available LPRS. The mean percent of left lung perfusion (LLP) was 42.7% (±6.7%). Excluding patients with pre‐existing LPA stenosis, 17% had abnormally decreased LLP. On hemodynamic measurements, 62 patients had available direct pressure measurements following PDA closure. None had significant increase. No correlation was found with echocardiographic data. Conclusion: PDA closure with Amplatzer family of devices is associated with a relatively significant risk of decreased perfusion to the left lung, mostly mild abnormalities. Comparison with catheterization and echocardiographic measurements showed lack of correlation with LPRS findings.© 2010 Wiley‐Liss, Inc.
Total aorto‐ostial chronic occlusion of the right coronary artery successfully recanalized via retrograde approach
Authors: Londoño Juan C. , Singh Vikas , O'Neill William W.
Published: January 2011

Chronic total occlusions remain a technical challenge for interventional cardiologists. This group of lesions carries a decreased rate of success and continues to be an important reason for surgical revascularization. Recently, retrograde percutaneous coronary intervention of total occlusions via epicardial and septal perforators was introduced as an alternative approach when a previous antegrade attempt has failed. We describe a unique case where retrograde approach was used as the initial recanalization technique in the absence of a right coronary ostium.© 2010 Wiley‐Liss, Inc.
Second‐Generation Iminoxylitol‐Based Pharmacological Chaperones for the Treatment of Gaucher Disease
Authors: Oulaïdi Farah , Front‐Deschamps Sophie , Gallienne Estelle , Lesellier Eric , Ikeda Kyoko , Asano Naoki , Compain Philippe , Martin Olivier R.
Published: January 2011

A series of O‐alkyl iminoxylitol derivatives was synthesized and evaluated as β‐glucocerebrosidase (GCase) inhibitors. This structure–activity study shows a dramatic influence of the position of the alkyl chain (α‐C1, O2, O3, or O4) on human GCase inhibition. Remarkably, 1,2‐shift of the alkyl chain from C1 to O2 was found to maintain high inhibitory potency toward GCase as well as chaperone activity at sub‐inhibitory concentration (10 nM). Removal of the stereogenic center at the pseudo‐anomeric position led to shorter and more practical synthetic sequences. 2‐O‐Alkyl iminoxylitol derivatives constitute a new promising class of leads for the treatment of Gaucher disease by means of pharmacological chaperone therapy.
2‐Amino‐3,4,5‐Trimethoxybenzophenones as Potent Tubulin Polymerization Inhibitors
Authors: Chuang Hsun‐Yueh , Chang Jang‐Yang , Lai Mei‐Jung , Kuo Ching‐Chuan , Lee Hsueh‐Yun , Hsieh Hsing‐Pang , Chen Ying‐Jen , Chen Li‐Tzong , Pan Wen‐Yu , Liou Jing‐Ping
Published: January 2011

A series of novel 2‐amino‐3,4,5‐trimethoxybenzophenone analogues exhibited excellent activity as tubulin polymerization inhibitors by targeting the colchicine binding site of microtubules. The lead compound 17 exhibited an IC50 value of 1.6 μM, similar to that of combretastatin A‐4 (IC50=1.9 μM). It also displayed remarkable anti‐proliferative activity, with IC50 values ranging from 7–16 nM against a variety of human cancer cell lines and one MDR(+) cancer cell line. SAR information indicated that the introduction of an amino group at the C2 position of benzophenone ring A and the C3’ position of benzophenone ring B play important roles in maximizing activity.
Thermodynamic Methods and Models to Study Flexible Metal–Organic Frameworks
Authors: Coudert François‐Xavier , Boutin Anne , Jeffroy Marie , Mellot‐Draznieks Caroline , Fuchs Alain H.
Published: January 2011

Much attention has recently been focused on a fascinating subclass of metal‐organic frameworks that behave in a remarkable stimuli‐responsive fashion. These soft porous crystals feature dynamic crystalline frameworks displaying reversible, large‐amplitude structural deformations under external physical constraints such as temperature, electric field or gas exposure. The number of reported syntheses of such materials is rapidly growing and they are promising for practical applications, such as gas capture, purification and fluid separation. Herein, we summarize the recently developed thermodynamic tools that can help understand the process of fluid adsorption and fluid mixture coadsorption in these flexible nanoporous materials. These tools, which include both molecular simulation methods and analytical models, can help rationalize experimental results and predict adsorption properties over a wide range of thermodynamic conditions. A particular focus is given on how these methods can guide the experimental exploration of a large number of materials and working conditions (temperature, pressure, composition) to help design efficient processes relying on fluid adsorption in soft porous crystals.
Extraordinarily Efficient Conduction in a Redox‐Active Ionic Liquid
Authors: Thorsmølle Verner K. , Rothenberger Guido , Topgaard Daniel , Brauer Jan C. , Kuang Dai‐Bin , Zakeeruddin Shaik M. , Lindman Björn , Grätzel Michael , Moser Jacques‐E.
Published: January 2011

Iodine added to iodide‐based ionic liquids leads to extraordinarily efficient charge transport, vastly exceeding that expected for such viscous systems. Using terahertz time‐domain spectroscopy, in conjunction with dc conductivity, diffusivity and viscosity measurements we unravel the conductivity pathways in 1‐methyl‐3‐propylimidazolium iodide melts. This study presents evidence of the Grotthuss mechanism as a significant contributor to the conductivity, and provides new insights into ion pairing processes as well as the formation of polyiodides. The terahertz and transport results are reunited in a model providing a quantitative description of the conduction by physical diffusion and the Grotthuss bond‐exchange process. These novel results are important for the fundamental understanding of conduction in molten salts and for applications where ionic liquids are used as charge‐transporting media such as in batteries and dye‐sensitized solar cells.
The emerging role of NO and IGF‐1 in early renal hypertrophy in STZ‐induced diabetic rats
Authors: Levin‐Iaina Nomy , Iaina Adrian , Raz Itamar
Published: January 2011

Background

Diabetic nephropathy (DN) is a major complication of diabetes mellitus, and the most common cause of end‐stage renal disease. DN is characterized by early hyperfiltration and renal hypertrophy, which are associated with increased renal insulin‐like growth factor‐1 (IGF‐1) levels. The relationship between IGF‐1 and nitric oxide (NO) in DN is not established. The aim of this study was to investigate the effects of NO system modulation on the IGF‐1‐mediated hypertrophy and hyperfiltration during the first week after diabetes induction.

Methods

Diabetes was induced in rats by streptozotocin (STZ) injection. Diabetic rats were treated with NO synthase inhibitor L‐NG‐nitroarginine methyl ester (L‐NAME). Various serum IGF‐binding proteins (IGFBPs) and renal IGFBP1 expression was evaluated. Urine and plasma NO2 + NO3 level analysis was also performed.

Results

STZ induced hyperglycaemia decreased plasma insulin levels and brought about a decrease in body weight. L‐NAME administration to diabetic rats significantly prevented renal hypertrophy and hyperfiltration. Serum IGFBP3, IGFBP4 and 30‐kDa IGFBP fraction were all significantly reduced in diabetic rats, compared with those in non‐diabetic control rats. However, the renal IGFBP1 mRNA expression in diabetic rats was significantly higher. These changes were accompanied by an increased in NO production. L‐NAME administration prevented the serum IGFBP decline, without significantly affecting the renal IGFBP1 mRNA expression.

Conclusions

We have shown that increased renal IGF‐1 and increased NO production during the very early stages of STZ‐induced DN are associated with renal hypertrophy and hyperfiltration in diabetic rats. Modulating the IGF‐1 availability to the kidney by nitric oxide synthase inhibition significantly reduced renal hypertrophy and hyperfiltration during the first week of STZ‐induced diabetes mellitus. Copyright © 2011 John Wiley & Sons, Ltd.
α4β2 nicotinic acetylcholine receptors in the early postnatal mouse superior cervical ganglion
Authors: Scholze Petra , Ciuraszkiewicz Anna , Groessl Florian , Orr‐Urtreger Avi , McIntosh J. Michael , Huck Sigismund
Published: January 2011

Heteropentameric nicotinic acetylcholine receptors (nAChR) mediate fast synaptic transmission in ganglia of the autonomic nervous system. It is undisputed that α3 and β4 are the predominant subunits in the superior cervical ganglion (SCG); however, reports on the presence of receptors that contain α4 have been controversial. Here, we have searched for the presence of α4‐containing nAChRs in the postnatal rat and mouse SCG. We now show by immunoprecipitation combined with radioligand binding that α4‐containing receptors constitute about 20% of hetero‐oligomeric nAChRs in postnatal Day 3 (P3) mice. However, already by P9, the level of α4 approaches zero. In contrast, the number of α4‐containing receptors is close to zero in the rat SCG at all times investigated. Deletion of the β2 subunit by using α5β2‐double knockout (KO) mice removes all α4‐containing receptors, suggesting that in the postnatal mouse SCG, α4 co‐assembles only with β2 but not with β4. α4β2 receptors are, on the other hand, up‐regulated in the SCG of P3 α5β4‐double KO mice, where they make up about 50% of receptors that bind [3H]‐epibatidine. Nonetheless, receptors on the surface of SCG neurons from α5β4‐double KO mice maintained for one to two days in culture comprise <10% of α4β2 and >90% of α3β2, as determined by patch clamp recordings with α4β2‐ and α3β2‐specific ligands. We propose that in the P3 SCG of wild type mice, α3β4 (±α5) represent about 62% of receptors, whereas 17% are α3β2β4, and 21% are α4β2 (±α5) receptors. © 2011 Wiley Periodicals, Inc. Develop Neurobiol 71: 390–399, 2011
Ly6C supports preferential homing of central memory CD8+ T cells into lymph nodes
Authors: Hänninen Arno , Maksimow Mikael , Alam Catharina , Morgan David J. , Jalkanen Sirpa
Published: January 2011

Ly6C is a murine cell‐surface antigen expressed by plasma cells, subsets of myeloid cells and many T cells, including memory T cells. We previously documented that Ly6C crosslinking induces LFA‐1 clustering on naïve CD8+ T cells. Here, we show that in vitro and in vivo differentiation of naïve CD8+ T cells into central (Tcm) but not effector (Tem) memory T cells enhances Ly6C expression, and its crosslinking induces strong LFA‐1 clustering on Tcm. Blocking Ly6C function inhibits in vivo Tcm homing to LNs as efficiently as blocking L‐selectin but it does not potentiate the inhibition provided by blocking either L‐selectin or LFA‐1 function. Thus, Ly6C, L‐selectin and LFA‐1 all appear to be part of a common homing pathway. In vitro, Ly6C crosslinking enhances Tcm adherence to ICAM‐1 in the presence of CCL21. In summary, Tcm homing involves Ly6C, in addition to L‐selectin and LFA‐1, and appears to potentiate firm adhesion of Tcm to ICAM‐1 in synergy with a chemokine. We propose that Ly6C augments Tcm compartmentalization into LNs during their homing.
A poxviral homolog of the Pellino protein inhibits Toll and Toll‐like receptor signalling
Authors: Griffin Bryan D. , Mellett Mark , Campos‐Torres Antonio , Kinsella Gemma K. , Wang Bingwei , Moynagh Paul N.
Published: January 2011

Toll‐like receptor (TLR) signalling pathways constitute an evolutionarily conserved component of the host immune response to pathogenic infection. Here, we describe the ability of a virally encoded form of the Pellino protein to inhibit Toll‐ and TLR‐mediated activation of downstream Rel family transcription factors. In addition to inhibiting drosomycin promoter activation by Spätzle in Drosophila melanogaster cells, viral Pellino attenuates the activation of NF‐κB by TLR signalling components and by the TLR4 ligand, LPS, in human cells. We propose that viral Pellino, like mammalian Pellinos, contains a forkhead‐associated domain but differs from the mammalian forms in that it lacks a complete and functional RING‐like domain. We produce a homology model and present experimental data to support this model by demonstrating that, like mammalian Pellinos, viral Pellino can interact with IRAK‐1 via its forkhead‐associated domain, whereas unlike its mammalian counterparts, it fails to post‐translationally modify IRAK‐1. Furthermore, we demonstrate that viral Pellino can functionally antagonise the activity of human Pellino3S. Thus, our findings identify potential immunoevasive capabilities possessed by a poxviral homolog of the Pellino protein and add growing evidence for a likely role for Pellino proteins in Toll and TLR signalling.
IFN‐α‐producing PDCA‐1+Siglec‐H− B cells mediate innate immune defense by activating NK cells
Authors: Bao Yan , Han Yanmei , Chen Zhubo , Xu Sheng , Cao Xuetao
Published: January 2011

B cells have multiple functions in adaptive immunity, including antibody production, antigen presentation and regulation of T‐cell responses. Recent evidences indicate that B cells have more subsets than previously thought and may have non‐classical functions, such as involvement in innate immunity and immune regulation; however, how B cells respond to microbial infection and elicit innate defense remain unclear. In this study, we identified a new subset of PDCA‐1+Siglec‐H−CD19+ B cells in mice during the early period of bacterial infection with Listeria monocytogenes. PDCA‐1+Siglec‐H−CD19+ B cells secreted large amounts of IFN‐α and thus facilitated IFN‐γ production and cytotoxicity function of natural killer (NK) cells via IFN‐α. B‐cell‐deficient Btk−/− mice were incapable of producing PDCA‐1+CD19+ B cells, and were more sensitive to L. monocytogenes infection. Adoptive transfer of PDCA‐1+CD19+ B cells to Btk−/− mice normalized their resistance to L. monocytogenes infection. Furthermore, we found that macrophages were essential for the inducible generation of PDCA‐1+Siglec‐H−CD19+ B cells via CD40‐CD40L ligation. Therefore, we have identified a new subset of PDCA‐1+Siglec‐H−CD19+ B cells, which enhances innate immune responses against bacterial infection by activating NK cells via secretion of IFN‐α.
Lymphotoxin‐β receptor‐independent development of intestinal IL‐22‐producing NKp46+ innate lymphoid cells
Authors: Satoh‐Takayama Naoko , Lesjean‐Pottier Sarah , Sawa Shinichiro , Vosshenrich Christian A. J. , Eberl Gérard , Di Santo James P.
Published: January 2011

The natural cytotoxicity receptor NKp46 is an activating receptor expressed by several distinct innate lymphoid cell (ILC) subsets, including NK cells, some γδ T cells and intestinal RORγt+IL‐22+ cells (NCR22 cells, IL‐22‐producing NKp46+ cell). NCR22 cells may play a role in mucosal barrier function through IL‐22‐mediated production of anti‐bacterial peptides from intestinal epithelial cells. Previous studies identified a predominant proportion of NCR22 cells in gut cryptopatches (CP), lymphoid structures that are strategically positioned to collect and integrate signals from luminal microbes; however, whether CP or other lymphoid structures condition NCR22 cell differentiation is not known. Programmed and inducible lymphoid tissue development requires cell‐surface‐expressed lymphotoxin (LT)α1β2 heterotrimers (provided by lymphoid tissue inducer (LTi) cells) to signal lymphotoxin‐β receptor (LTR)+ stromal cells. Here, we analyzed NCR22 cells in LTβR‐deficient Ncr1GFP/+ mice that lack organized secondary lymphoid tissues. We found that NCR22 cells develop in the absence of LTβR, become functionally competent and localize to the lamina propria under steady‐state conditions. Following infection of LTβR−/− mice with the Gram‐negative pathogen Citrobacter rodentium, IL‐22 production from NCR22 cells was not affected. These results indicate that organized lymphoid tissue structures are not critical for the generation of an intact and fully functional intestinal NCR22 cell compartment.
TET inducible expression of the α4β7‐integrin ligand MAdCAM‐1 on the blood–brain barrier does not influence the immunopathogenesis of experimental autoimmune encephalomyelitis
Authors: Döring Axinia , Pfeiffer Friederike , Meier Matthias , Dehouck Bénédicte , Tauber Silke , Deutsch Urban , Engelhardt Britta
Published: January 2011

Inhibiting the α4 subunit of the integrin heterodimers α4β1 and α4β7 with the mab natalizumab is an effective treatment of multiple sclerosis (MS). Which of the two α4 heterodimers is involved in disease pathogenesis has, however, remained controversial. Whereas the development of experimental autoimmune encephalomyelitis (EAE), an animal model of MS, is ameliorated in β7‐integrin‐deficient C57BL/6 mice, neutralizing antibodies against the β7‐integrin subunit or the α4β7‐integrin heterodimer fail to interfere with EAE pathogenesis in the SJL mouse. To facilitate α4β7‐integrin‐mediated immune‐cell trafficking across the blood–brain barrier (BBB), we established transgenic C57BL/6 mice with endothelial cell‐specific, inducible expression of the α4β7‐integrin ligand mucosal addressin cell adhesion molecule (MAdCAM)‐1 using the tetracycline (TET)‐OFF system. Although TET‐regulated MAdCAM‐1 induced α4β7‐integrin mediated interaction of α4β7+/α4β1− T cells with the BBB in vitro and in vivo, it failed to influence EAE pathogenesis in C57BL/6 mice. TET‐regulated MAdCAM‐1 on the BBB neither changed the localization of central nervous system (CNS) perivascular inflammatory cuffs nor did it enhance the percentage of α4β7‐integrin+ inflammatory cells within the CNS during EAE. In conclusion, our study demonstrates that ectopic expression of MAdCAM‐1 at the BBB does not increase α4β7‐integrin‐mediated immune cell trafficking into the CNS during MOGaa35–55‐induced EAE.
CX3CR1 defines functionally distinct intestinal mononuclear phagocyte subsets which maintain their respective functions during homeostatic and inflammatory conditions
Authors: Weber Benjamin , Saurer Leslie , Schenk Mirjam , Dickgreber Nina , Mueller Christoph
Published: January 2011

Intestinal mononuclear phagocytes (iMNP) are critically involved in mucosal immunity and tissue homeostasis. Two major non‐overlapping populations of iMNP have been identified in mice. CD103+ iMNP represent a migratory population capable of inducing tolerogenic responses, whereas CX3CR1+ iMNP are resident cells with disease‐promoting potential. CX3CR1+ iMNP can further be subdivided based on differential expression of CX3CR1. Using CX3CR1GFP/+×RAG2−/− mice, we demonstrate that CX3CR1hi and CX3CR1lo iMNP clearly differ with respect to their morphological and functional properties. Compared with CX3CR1hi iMNP, CX3CR1lo iMNP are polarised towards pro‐inflammatory responses already under homeostatic conditions. During a CD4+ T‐cell‐induced colitis, CX3CR1lo cells accumulate in the inflamed mucosa and upregulate the expression of pro‐inflammatory cytokines and triggering receptor expressed on myeloid cells‐1 (TREM‐1). In contrast, CX3CR1hi iMNP retain their non‐inflammatory profile even during intestinal inflammation. These findings identify two functionally distinct iMNP subsets based on differential expression of CX3CR1 and indicate an unanticipated stability of iMNP.