bluuebunny/crossref_metadata_2025_split huggingface dataset:
Kinetics Studies on the Inhibition Mechanism of Pancreatic α‐Amylase by Glycoconjugated 1H‐1,2,3‐Triazoles: A New Class of Inhibitors with Hypoglycemiant Activity
Authors: Senger Mario Roberto , Gomes Lucas da Costa Andrade , Ferreira Sabrina Baptista , Kaiser Carlos Roland , Ferreira Vitor Francisco , Silva Floriano Paes 
Published: June 2012

AbstractGlycoconjugated 1H‐1,2,3‐triazoles (GCTs) comprise a new class of glycosidase inhibitors that are under investigation as promising therapeutic agents for a variety of diseases, including type 2 diabetes mellitus. However, few kinetics studies have been performed to clarify the mode of inhibition of GCTs with their target glycosidases. Our group has previously shown that some methyl‐β‐D‐ribofuranosyl‐1H‐1,2,3‐triazoles that inhibit baker's yeast maltase were also able to reduce post‐prandial glucose levels in normal rats. We hypothesized that this hypoglycemiant activity was attributable to inhibition of mammalian α‐glucosidases involved in sugar metabolism, such as pancreatic α‐amylase. Hence, the aim of this work was to test a series of 26 GCTs on porcine pancreatic α‐amylase (PPA) and to characterize their inhibition mechanisms. Six GCTs, all ribofuranosyl‐derived GCTs, significantly inhibited PPA, with IC50 values in the middle to high micromolar range. Our results also demonstrated that ribofuranosyl‐derived GCTs are reversible, noncompetitive inhibitors when using 2‐chloro‐4‐nitrophenyl‐α‐D‐maltotrioside as a substrate. E/ES affinity ratios (α) ranged from 0.3 to 1.1, with the majority of ribofuranosyl‐derived GCTs preferentially forming stable ternary ESI complexes. Competition assays with acarbose showed that ribofuranosyl‐derived GCTs bind to PPA in a mutually exclusive fashion. The data presented here show that pancreatic α‐amylase is one of the possible molecular targets in the pharmacological activity of ribofuranosyl‐derived GCTs. Our results also provide important mechanistic insight that can be of major help to develop this new class of synthetic small molecules into more potent compounds with anti‐diabetic activity through rational drug design.
Transventricular balloon dilation and stenting of the RVOT in small infants with tetralogy of fallot with pulmonary atresia
Authors: Cools Bjorn , Boshoff Derize , Heying Ruth , Rega Filip , Meyns Bart , Gewillig Marc 
Published: June 2012

IntroductionThe management of small infants with tetralogy of Fallot (TOF) with pulmonary atresia (PA) and hypoplastic pulmonary arteries can be very challenging.MethodsIn three small infants (weight range 2,200–3,600 g, pulmonary trunk 2.0–3.2 mm), initial palliation consisted of sternotomy, transventricular puncture of the right ventricular outflow tract and atretic pulmonary valve, followed by balloon dilation (n = 1) or stent deployment (n = 2) from the right ventricle into the pulmonary trunk (stent diameter 5–6 mm, length 16 mm).ResultsThe procedure resulted in adequate palliation with good anterograde flow to the pulmonary arteries and near normal saturations in all three patients (>92%); there was no associated morbidity. Additional transvenous stenting was required in all patients because of progressive muscular infundibular stenosis after a median of 3 months. Two patients evolved to full repair at the age of 5 months and one patient with multiple hilar stenoses requires additional percutaneous procedures through the stented RV outflow tract.ConclusionTransventricular balloon dilation and stenting of the RVOT through medial sternotomy as initial palliation strategy appears a safe and well tolerated alternative treatment in small infants with TOF with PA and a hypoplastic pulmonary trunk. © 2013 Wiley Periodicals, Inc.
Mechanics of the foot Part 2: A coupled solid–fluid model to investigate blood transport in the pathologic foot
Authors: Mithraratne K. , Ho H. , Hunter P.J. , Fernandez J.W. 
Published: June 2012

SUMMARYA coupled computational model of the foot consisting of a three‐dimensional soft tissue continuum and a one‐dimensional (1D) transient blood flow network is presented in this article. The primary aim of the model is to investigate the blood flow in major arteries of the pathologic foot where the soft tissue stiffening occurs. It has been reported in the literature that there could be up to about five‐fold increase in the mechanical stiffness of the plantar soft tissues in pathologic (e.g. diabetic) feet compared with healthy ones. The increased stiffness results in higher tissue hydrostatic pressure within the plantar area of the foot when loaded. The hydrostatic pressure acts on the external surface of blood vessels and tend to reduce the flow cross‐section area and hence the blood supply. The soft tissue continuum model of the foot was modelled as a tricubic Hermite finite element mesh representing all the muscles, skin and fat of the foot and treated as incompressible with transversely isotropic properties. The details of the mechanical model of soft tissue are presented in the companion paper, Part 1. The deformed state of the soft tissue continuum because of the applied ground reaction force at three foot positions (heel‐strike, midstance and toe‐off) was obtained by solving the Cauchy equations based on the theory of finite elasticity using the Galerkin finite element method. The geometry of the main arterial network in the foot was represented using a 1D Hermite cubic finite element mesh. The flow model consists of 1D Navier–Stokes equations and a nonlinear constitutive equation to describe vessel radius–transmural pressure relation. The latter was defined as the difference between the fluid and soft tissue hydrostatic pressure. Transient flow governing equations were numerically solved using the two‐step Lax–Wendroff finite difference method. The geometry of both the soft tissue continuum and arterial network is anatomically‐based and was developed using the data derived from visible human images and magnetic resonance images of a healthy male volunteer. Simulation results reveal that a two‐fold increase in tissue stiffness leads to about 28% reduction in blood flow to the affected region.Copyright © 2012 John Wiley & Sons, Ltd.
Singlet Carbenes Derived from Ferrocene and Closely Related Sandwich Complexes
Authors: Siemeling Ulrich 
Published: June 2012

AbstractThis microreview describes the tremendous progress that has been made during the past decade in the area of ferrocene‐based singlet carbenes, the vast majority of which belong to the family of N‐heterocyclic carbenes (NHCs). The ferrocene motif is present in such NHCs either as a ferrocenyl (Fc) substituent or a 1,1′‐ferrocenediyl (fc) backbone. In terms of applications, the modification of popular ferrocene‐based chiral P ligands by following the phosphane‐NHC analogy has been an important guideline for much of the work directed towards catalysis. A particularly exciting development has occurred with NHCs that contain an fc backbone, since these compounds have proved to be capable of small‐molecule activation. The recent development of singlet carbenes that are not based on ferrocene but rather on related ruthenium sandwich complexes demonstrates the wide scope and highly dynamic nature of the field.
Electrophilic Cyclization of 2‐(2′,3′‐Allenyl)acetylacetates with Iodine Using Calcium Hydride as the Base
Authors: Wan Baoqiang , Jiang Xuefeng , Jia Guochen , Ma Shengming 
Published: June 2012

AbstractA facile and efficient protocol for the synthesis of 4,5‐dihydrofuran derivatives via iodine‐mediated cyclization of various 2‐(2′,3′‐allenyl)acetylacetates with CaH2 as the base has been developed. The yields range from moderate to good. The resulting products can be used for further elaboration by palladium‐catalyzed coupling reactions.
Enantioselective Synthesis of (R)‐Homoboroproline from (S)‐Proline Using a Borylation Approach
Authors: Georgiou Irene , Whiting Andrew 
Published: June 2012

Abstract(S)‐Proline was converted through a five‐step sequence into (R)‐homoboroproline hydrochloride in 29 % overall yield with 97 % ee The key step was the conversion of N‐Boc iodomethylpyrrolidine into the corresponding pinacol boronate ester by an efficient copper(I)‐catalyzed borylation reaction by using bispinacolatodiboron.
Carbon black nanoparticle intratracheal installation results in large and sustained changes in the expression of miR‐135b in mouse lung
Authors: Bourdon Julie A. , Saber Anne T. , Halappanavar Sabina , Jackson Petra A. , Wu Dongmei , Hougaard Karin S. , Jacobsen Nicklas R. , Williams Andrew , Vogel Ulla , Wallin Håkan , Yauk Carole L. 
Published: June 2012

AbstractMicroRNAs (miRNA) are important noncoding regulatory molecules that bind target messenger RNA (mRNA), primarily affecting their translation into protein. Because miRNAs can simultaneously target hundreds of mRNAs, subtle changes in their expression can elicit important cellular effects. Little is known about the role of miRNAs in pulmonary responses to inhaled particulate matter. We studied pulmonary global miRNA responses to Printex 90 carbon black nanoparticles in (1) nonpregnant C57BL/6 female mice instilled with vehicle or a single dose of 0.162 mg and euthanized 1, 3, and 28 days post‐exposure, and (2) C57BL/6Bom Tac dams instilled with vehicle or a cumulative dose of 0.268 mg (four separate instillations of vehicle or 0.067 mg Printex 90 during pregnancy) and euthanized at weaning (26–27 days postexposure). We measured similar expression profiles in both exposure scenarios, with marked increases in miR‐135b and subtle changes in miR‐21 and miR‐146b. All three miRNAs were confirmed in nonpregnant females by RT‐PCR, whereas only miR‐135b was confirmed in the dams. Target analysis revealed no concomitant changes in established and predicted targets of miR‐135b, miR‐21, or miR‐146b. Analysis of potentially perturbed pathways did not reveal changes that would suggest down‐stream miRNA effects. The reasons for the lack of association between miRNA and transcript profiles may be related to the complexity of miRNA function and fate, or to the possibility that targets may differ from those already established or predicted in silico. We hypothesize that changes in the expression of these miRNAs may be associated with resolution of pulmonary inflammation, but future work will be necessary to precisely identify specific targets of these miRNAs in lungs. Environ. Mol. Mutagen., 2012. © 2012 Wiley Periodicals, Inc.
ACB‐PCR measurement of H‐ras codon 61 CAA→CTA mutation provides an early indication of aristolochic acid I carcinogenic effect in tumor target tissues
Authors: Wang Yiying , Arlt Volker M. , Roufosse Candice A. , McKim Karen L. , Myers Meagan B. , Phillips David H. , Parsons Barbara L. 
Published: June 2012

AbstractAristolochic acid (AA) is a strong cytotoxic nephrotoxin and carcinogen, which induces forestomach and kidney tumors in mice and is associated with development of urothelial cancer in humans. This study sought to gain mechanistic insight into AAI‐induced carcinogenesis through analysis of a tumor‐relevant endpoint. Female Hupki mice were treated daily with 5 mg AAI/kg body weight by gavage for 3, 12, or 21 days. Histopathology and DNA adduct analysis confirmed kidney and forestomach as target tissues for AAI‐induced toxicity. H‐ras codon 61 CAA→CTA mutations were measured in mouse kidney and forestomach, as well as liver and glandular stomach (nontarget organs) by allele‐specific competitive blocker‐PCR (ACB‐PCR), because A→T transversion is the predominant mutation induced by AA and this particular mutation was found previously in AA‐induced rodent forestomach tumors. Treatment‐related differences were observed, with the H‐ras mutant fraction (MF) of mouse kidney and forestomach exposed to 5 mg AAI/kg body weight for 21 days significantly higher than that of vehicle‐treated controls (Fisher's exact test, P < 0.05). Statistically significant correlations between dA‐AAI adduct levels (measured previously in the same animals) and induced H‐ras MFs were evident in forestomach of mice treated for 21 days (linear regression, P < 0.05). The significant increase in H‐ras MF in kidney and forestomach, along with the correlation between DNA adducts, histopathology, and oncogene mutation, provide definitive evidence that AA induces tumors through a directly mutagenic mode of action. Thus, measurement of tumor‐associated mutations is a useful tool for elucidating the mechanisms underlying the tissuespecificity of carcinogenesis. Environ. Mol. Mutagen. 2012. © 2012 Wiley Periodicals, Inc.
Ubiquitylation in immune disorders and cancer: from molecular mechanisms to therapeutic implications
Authors: Fulda Simone , Rajalingam Krishnaraj , Dikic Ivan 
Published: June 2012

AbstractConjugation of ubiquitin to proteins (ubiquitylation) has emerged to be one of the most crucial post‐translational modifications controlling virtually all cellular processes. What was once regarded as a mere signal for protein degradation has turned out to be a major regulator of molecular signalling networks. Deregulation of ubiquitin signalling is closely associated with various human pathologies. Here, we summarize the current knowledge of ubiquitin signalling in immune deficiencies and cancer as well as the available therapeutic strategies targeting the ubiquitin system in combating these pathogenic conditions.
Loss of stromal androgen receptor leads to suppressed prostate tumourigenesis via modulation of pro‐inflammatory cytokines/chemokines
Authors: Lai Kuo‐Pao , Yamashita Shinichi , Huang Chiung‐Kuei , Yeh Shuyuan , Chang Chawnshang 
Published: June 2012

AbstractStromal–epithelial interaction is crucial to mediate normal prostate and prostate cancer (PCa) development. The indispensable roles of mesenchymal/stromal androgen receptor (AR) for the prostate organogenesis have been demonstrated by using tissue recombination from wild‐type and testicular feminized mice. However, the stromal AR functions in the tumour microenvironment and the underlying mechanisms governing the interactions between the epithelium and stroma are not completely understood. Here, we have established the first animal model with AR deletion in stromal fibromuscular cells (dARKO, AR knockout in fibroblasts and smooth muscle cells) in the Pten+/− mouse model that can spontaneously develop prostatic intraepithelial neoplasia (PIN). We found that loss of stromal fibromuscular AR led to suppression of PIN lesion development with alleviation of epithelium proliferation and tumour‐promoting microenvironments, including extracellular matrix (ECM) remodelling, immune cell infiltration and neovasculature formation due, in part, to the modulation of pro‐inflammatory cytokines/chemokines. Finally, targeting stromal fibromuscular AR with the AR degradation enhancer, ASC‐J9®, resulted in the reduction of PIN development/progression, which might provide a new approach to suppress PIN development.
Arctic rockwall retreat rates estimated using laboratory‐calibrated ERT measurements of talus cones in Longyeardalen, Svalbard
Authors: Siewert Matthias Benjamin , Krautblatter Michael , Christiansen Hanne Hvidtfeldt , Eckerstorfer Markus 
Published: June 2012

ABSTRACTHolocene rockwall retreat rates quantify integral values of rock slope erosion and talus cone evolution. Here we investigate Holocene rockwall retreat of exposed arctic sandstone cliffs in Longyeardalen, central Svalbard and apply laboratory‐calibrated electrical resistivity tomography (ERT) to determine talus sediment thickness. Temperature–resistivity functions of two sandstone samples are measured in the laboratory and compared with borehole temperatures from the talus slope. The resistivity of the higher and lower‐porosity sandstone at relevant borehole permafrost temperatures defines a threshold range that accounts for the lithological variability of the dominant bedrock and debris material. This helps to estimate the depth of the transition from higher resistivities of ice‐rich debris to lower resistivities of frozen bedrock in the six ERT transects. The depth of the debris–bedrock transition in ERT profiles is confirmed by a pronounced apparent resistivity gradient in the raw data plotted versus depth of investigation. High‐resolution LiDAR‐scanning and ERT subsurface information were collated in a GIS to interpolate the bedrock surface and to calculate the sediment volume of the talus cones. The resulting volumes were referenced to source areas to calculate rockwall retreat rates. The rock mass strength was estimated for the source areas. The integral rockwall retreat rates range from 0.33 to 1.96 mm yr–1, and are among the highest rockwall retreat rates measured in arctic environments, presumably modulated by harsh environmental forcing on a porous sandstone rock cliff with a comparatively low rock mass strength. Here, we show the potential of laboratory‐calibrated ERT to provide accurate estimates of rockwall retreat rates even in ice‐rich permafrost talus slopes. Copyright © 2012 John Wiley & Sons, Ltd.
In vitro apoptotic effects of methanol extracts of Dianthus chinensis and Acalypha australis L. targeting specificity protein 1 in human oral cancer cells
Authors: Shin Ji‐Ae , Kim Jae‐Jin , Choi Eun‐Sun , Shim Jung‐Hyun , Ryu Mi Heon , Kwon Ki Han , Park Hee‐Min , Seo Jin‐Young , Lee Soo‐Yeon , Lim Do‐Won , Cho Nam‐Pyo , Cho Sung‐Dae 
Published: June 2012

AbstractBackgroundThe aims of this study were to evaluate the apoptotic activities and molecular mechanisms of methanol extracts of Dianthus chinensis (MEDC) and Acalypha australis L. (MEAL) in human oral cancer cells.MethodsThe apoptotic effects and related molecular mechanisms of MEDC and MEAL on oral cancer cells were evaluated using MTS assay, DAPI staining, immunostaining, Western blotting, and reverse transcriptase–polymerase chain reaction.ResultsSp1 was overexpressed in oral tumor tissues compared with normal oral mucosa. Downregulation of Sp1 inhibited the growth of SCC‐15 and YD‐15 oral cancer cells. MEDC and MEAL inhibited cell growth and induced apoptosis in both cell lines by decreasing the expression of Sp1. In addition, treatment of cells with MEDC and MEAL decreased Mcl‐1 expression, which is a downstream target of Sp1.ConclusionOur results indicate that MEDC and MEAL are bioactive natural products that can potentially induce apoptosis of tumor cells that overexpress the Sp1 protein. © 2012 Wiley Periodicals, Inc. Head Neck, 2013
The Role of Personal Loss in the Caregiving Experiences of Well Siblings of Adults With Serious Mental Illness
Authors: Leith Jaclyn E. , Stein Catherine H. 
Published: June 2012

ObjectiveThe present study examined the role of personal loss due to mental illness and meaning‐related coping strategies on reports of caregiving among well siblings of adults with serious mental illness.MethodA sample of 103 well siblings of adults with serious mental illness completed an online survey. Participants were recruited through websites related to mental illness and through contact with leaders of family support groups.ResultsPersonal loss, not meaning‐related coping, was the strongest predictor of current caregiving among well siblings. Well siblings’ age, support group affiliation, and perceived level of sibling dependence also contributed to variation in reports of current caregiving.ConclusionPersonal loss has powerful implications for research and interventions focused on sibling involvement in caregiving for adults with mental illness.
An Open Trial of Motivational Interviewing to Address Suicidal Ideation With Hospitalized Veterans
Authors: Britton Peter C. , Conner Kenneth R. , Maisto Stephen A. 
Published: June 2012

Objective:The purpose of this open trial was to test the acceptability of motivational interviewing to address suicidal ideation (MI‐SI) for psychiatrically hospitalized veterans with suicidal ideation, estimate its pre‐post effect size on the severity of suicidal ideation, and examine the rate of treatment engagement after discharge.Methods:Participants received a screening assessment, baseline assessment, one or two MI‐SI sessions, posttreatment assessment, and 60‐day follow‐up assessment. Thirteen veterans were enrolled, 9 (70%) completed both MI‐SI sessions and the posttreatment assessment, and 11 (85%) completed the follow‐up assessment.Results:Participants found MI‐SI to be acceptable. They experienced large reductions in the severity of suicidal ideation at posttreatment and follow‐up. In the 2 months following discharge, 73% of participants completed two or more mental health or substance abuse treatment sessions each month.Conclusions:These preliminary findings suggest that MI‐SI has potential to reduce risk for suicide in psychiatrically hospitalized veterans and that a more rigorous trial is needed. © 2012Wiley Periodicals, Inc. J. Clin. Psychol. 00:1‐11, 2012.
Unraveling the Influences of Soft‐Tissue Flipper Development on Skeletal Variation Using an Extinct Taxon
Authors: Maxwell Erin E. 
Published: June 2012

ABSTRACTAdaptation to an aquatic habitat results in dramatic changes in tetrapod limb morphology as limbs take on the roles of propulsion and steering and lose their weight‐bearing function. Changes include enclosure of the limb in a soft‐tissue flipper and proportional lengthening of the distal limb, often accomplished through the addition of skeletal elements (hyperphalangy). The flipper structure itself and changes to the developmental architecture permitting hyperphalangy are hypothesized to increase observed limb variation, based on a cetacean model. These hypotheses are examined in the ichthyosaurs Stenopterygius and Mixosaurus. Hyperphalangy combined with high levels of variation in phalangeal counts were observed in both genera. The amount of variation was not proportional to the number of phalanges in a digit, but was related to functional digit length. In addition, qualitative variants were catalogued in both genera. Polyphalangy, phalangeal fusion, and additional ossifications in the zeugopodial row were not observed in Mixosaurus, but were common in Stenopterygius, even though both genera exhibited a similar degree of hyperphalangy. These results suggest that while the flipper structure and processes resulting in hyperphalangy may increase observed variation in phalangeal counts, these factors are unlikely to be causing high levels of qualitative variation in ichthyosaurs. Patterns of variation in ichthyosaur limbs, and thus variability, are unique to species but can change over evolutionary time. J. Exp. Zool. (Mol. Dev. Evol.) 318B:545–554, 2012. © 2012 Wiley Periodicals, Inc.
What happens when you trust your supervisor? Mediators of individual performance in trust relationships
Authors: Li Alex Ning , Tan Hwee Hoon 
Published: June 2012

SummaryTo understand how trust in supervisor translates into individual job performance, we hypothesize that trust in supervisor facilitates positive psychological conditions of meaningfulness, safety, and availability, which in turn predict individual job performance. We assert that each of the three mediating paths in our model represents a distinct mechanism by which trust in supervisor contributes to individual job performance. We test our hypotheses with 206 supervisor–subordinate dyads and find that trust in supervisor contributes to job performance through psychological availability and psychological safety but not psychological meaningfulness. By examining three different psychological mechanisms within the same frame, we provide a test that compares and contrasts the uniqueness of the three pathways. Our findings suggest practical ways for managers to build trust with subordinates and guidance for the design of productive work conditions. Copyright © 2012 John Wiley & Sons, Ltd.