bluuebunny/crossref_metadata_2025 huggingface dataset:
The Optimal Flow Rate for Antegrade Cerebral Perfusion During Deep Hypothermic Circulatory Arrest
Authors: Chen Yan , Liu Jinping , Ji Bingyang , Tang Yue , Wu Aili , Wang Shilei , Zhou Chun , Long Cun
Published: July 2012

The aim of this study is to compare cerebral protection using antegrade cerebral perfusion (ACP) with various flow rates during deep hypothermic circulatory arrest (DHCA) in a piglet model. Twenty‐three piglets were randomized to five groups: the control group (n = 3), DHCA group (n = 5), ACP25 group (n = 5), ACP50 group (n = 5), and ACP80 group (n = 5). Three control piglets did not undergo operations. Twenty piglets underwent cardiopulmonary bypass (CPB) and DHCA for 60 min at 20°C. ACP was conducted at 0, 25, 50, and 80 mL/kg/min in the DHCA, ACP25, ACP50, and ACP80 group, respectively. Serum S‐100B protein and neuron‐specific enolase were monitored, and brain tissues were assayed for the activities of caspase‐3 and stained for the evidence of apoptotic cellular injury. Rise in serum S‐100B level (post‐CPB—pre‐CPB) in the ACP50 group was significantly lower than that in the ACP80 group (P = 0.001). Caspase‐3 levels were significantly elevated in the ACP80 group compared with the ACP25 (P = 0.041) and ACP50 group (P = 0.01), while positive terminal deoxyneucleotidyl transferase‐mediated biotin‐dUTP nick end labeling reaction scores in the ACP80 group were significantly higher than those in the ACP25 (P = 0.043) and ACP50 group (P = 0.023). Cerebral protection effects of ACP at 25 and 50 mL/kg/min were superior to that of ACP at 80 mL/kg/min as determined by cerebral markers, immunology, and histology.
A Novel Design of Spiral Groove Bearing in a Hydrodynamically Levitated Centrifugal Rotary Blood Pump
Authors: Han Qing , Zou Jun , Ruan Xiaodong , Fu Xin , Yang Huayong
Published: July 2012

Good washout is very important in spiral groove bearing (SGB) designs when applied to blood pumps due to the micrometer scales of lubrication films and groove depths. To improve washout, flow rate or leakage through SGBs should be as large as possible. However, this special goal violates conventional SGB designs in which no leakage is desired as the leakage would decrease load‐carrying capacity significantly. So, a design concept is formed fulfilling the two goals of high load‐carrying capacity and large flow rate: let groove width decrease along flow path and the mating surface of the rotor rotate with a direction facilitating the flow through the grooves. Under this concept, a novel SGB is designed, contrary to conventional ones, with groove width decreasing with increasing spiral radius. This SGB is mounted on the motionless upper plate of our designed centrifugal blood pump, with the mating surface of rotor rotating with a direction facilitating the outward flow. To assess SGB designs, a characteristic plane is originally presented relating to pressure‐normalized load‐carrying capacity and flow rate. Comparisons between various kinds of SGB designs are made, and computational fluid dynamics (CFD) results are plotted in this characteristic plane from which load/flow performances can be directly read out. CFD and comparison results show that the new designs have superior load/flow characteristics. However, the impact of SGB designs upon hemolysis/thrombus formation is still to be verified according to the concept presented.
Progress on the Design and Development of the Continuous‐Flow Total Artificial Heart
Authors: Kobayashi Mariko , Horvath David J. , Mielke Nicole , Shiose Akira , Kuban Barry , Goodin Mark , Fukamachi Kiyotaka , Golding Leonard A.R.
Published: July 2012

Cleveland Clinic's continuous‐flow total artificial heart has one motor and one rotating assembly supported by a hydrodynamic bearing. The right hydraulic output is self regulated by passive axial movement of the rotating assembly to balance itself with the left output. The purpose of this article is to present progress in four areas of development: the automatic speed control system, self‐regulation to balance right/left inlet pressures and flows, hemolysis testing using calf blood, and coupled electromagnetics (EMAG) and computational fluid dynamics (CFD) analysis. The relationships between functions of motor power and speed, systemic flow, and systemic vascular resistance (SVR) were used for the sensorless speed control algorithm and demonstrated close correlations. Based on those empirical relationships, systemic flow and SVR were calculated in the system module and showed good correlation with measured pump flow and SVR. The automatic system adjusted the pump's speed to obtain the target flow in response to the calculated SVR. Atrial pressure difference (left minus right atrial pressure) was maintained within ±10 mm Hg for a wide range of SVR/pulmonary vascular resistance ratios, demonstrating a wide margin of self‐regulation under fixed‐speed mode and 25% sinusoidally modulated speed mode. Hemolysis test results indicated acceptable values (normalized index of hemolysis <0.01 mg/dL). The coupled EMAG/CFD model was validated for use in further device development.
The Practitioner Proposes a Treatment Change and the Patient Declines: What to do next?
Authors: Falzer Paul R. , Leventhal Howard L. , Peters Ellen , Fried Terri R. , Kerns Robert , Michalski Marion , Fraenkel Liana
Published: July 2012

Abstract Objective:  This study describes how pain practitioners can elicit the beliefs that are responsible for patients’ judgments against considering a treatment change and activate collaborative decision making.

Methods:  Beliefs of 139 chronic pain patients who are in treatment but continue to experience significant pain were reduced to 7 items about the significance of pain on the patient’s life. The items were aggregated into 4 decision models that predict which patients are actually considering a change in their current treatment.

Results: While only 34% of study participants were considering a treatment change overall, the percentage ranged from 20 to 70, depending on their ratings about current consequences of pain, emotional influence, and long‐term impact. Generalized linear model analysis confirmed that a simple additive model of these 3 beliefs is the best predictor.

Conclusion:  Initial opposition to a treatment change is a conditional judgment and subject to change as specific beliefs become incompatible with patients’ current conditions. These beliefs can be elicited through dialog by asking 3 questions.
Carotid IMT Variability (IMTV) and Its Validation in Symptomatic versus Asymptomatic Italian Population: Can This Be a Useful Index for Studying Symptomaticity?
Authors: Saba Luca , Meiburger Kristen M. , Molinari Filippo , Ledda Giuseppe , Anzidei Michele , Acharya U. Rajendra , Zeng Guang , Shafique Shoaib , Nicolaides Andrew , Suri Jasjit S.
Published: July 2012

The carotid intima‐media thickness (IMT) is a validated marker of cerebrovascular disease risk. This paper presents a new parameter, the IMT variability (IMTV), and compares it between symptomatic and asymptomatic patients taken from a cohort of Italian population. One hundred forty‐two patients were analyzed (age 59 ± 112 years, 59% males), 42 of these patients suffered from TIA or minor stroke. The lumen‐intima (LI) and media‐adventitia (MA) interfaces of the far wall were manually traced by a Reader. We also used a computer‐based automated system (called AutoEdge) to obtain the LI/MA interfaces. The LI/MA interfaces were used to measure the IMT and the IMTV along the distal wall of the common carotid artery. Wilcoxon and Pearson correlation analyses were performed. The agreement between the Reader's IMT and the AutoEdge IMT values was 98.7% for the symptomatic (0.83 ± 0.44 mm for Reader, 0.82 ± 0.35 mm for AutoEdge) and 94.9% for the asymptomatic patients (0.78 ± 0.45 mm for Reader, 0.74 ± 0.30 mm for AutoEdge). Correlation was 65% for symptomatic and 68% for asymptomatic patients, respectively. The IMT measured using AutoEdge was 1.2% lower compared to manual measurements in symptomatic population, while 5.12% lower in asymptomatic. The IMTV was 11% higher in symptomatic patients compared to asymptomatic when using manual delineations, 8% higher when using AutoEdge. There was no statistical difference between the manual and automated IMTV measurements (Wilcoxon signed rank, P > 0.7). We conclude that the IMT and IMTV values were very similar between Reader and AutoEdge software when studying symptomatic and asymptomatic patients in Italian population.
Echocardiography as a Simple Initial Tool to Assess Right Ventricular Dimensions in Patients with Repaired Tetralogy of Fallot before Undergoing Pulmonary Valve Replacement: Comparison with Cardiovascular Magnetic Resonance Imaging
Authors: Chaowalit Nithima , Durongpisitkul Kritvikrom , Krittayaphong Rungroj , Komoltri Chulaluck , Jakrapanichakul Decho , Phrudprisan Suteera
Published: July 2012

Objective: Accurate assessment of the right ventricle (RV) is essential in patients with repaired tetralogy of Fallot (TOF). We proposed a simple echocardiographic method to assess the RV dimensions and evaluated the relationship between linear echocardiographic measures of the RV and RV volumes obtained by cardiovascular magnetic resonance imaging (CMR). Methods: A total of 45 patients (27.4 ± 11.2 years; 40% male) with repaired TOF underwent CMR and echocardiography. Using echocardiography, RV dimensions were assessed from the parasternal short‐axis view using the longest RV internal diameter perpendicular to the mid‐interventricular septum. Significant RV dilatation was defined as an RV end‐diastolic volume index >160 mL/m2 on CMR. Results: There were significant correlations between RV dimensions determined by echocardiography and the pulmonary regurgitation fraction, RV size, and function determined by CMR. The cutoff values of echocardiographic RV outflow tract (RVOT), end‐systolic and end‐diastolic dimension indices, and the combination of RVOT and end‐diastolic dimension indices to determine significant RV dilatation were 19.0, 19.4, 24.5, and 45.2 mm/m2, respectively. The positive and negative predictive values for significant RV dilatation were 89.7% and 68.8% with RVOT diameter index ≥19.0 mm/m2, 85.0% and 52.4% with RV end‐systolic dimension index ≥19.4 mm/m2, 87.5% and 64.7% with RV end‐diastolic dimension index ≥24.5 mm/m2, and 92.3% and 80.0% with the combination of RVOT and end‐diastolic dimension indices ≥45.2 mm/m2, respectively. Conclusion: Echocardiography can be used to assess RV size in patients with repaired TOF with acceptable correlations with CMR as the reference standard.
Loss of Left Ventricular Torsion as the Predominant Mechanism of Left Ventricular Systolic Dysfunction in a Patient with Tubercular Cardiomyopathy
Authors: Bansal Manish , Mehrotra Rahul , Kasliwal Ravi R.
Published: July 2012

Pericarditis is the commonest form of cardiac involvement in tuberculosis whereas myocardial involvement is exceedingly rare. We hereby report a patient who presented with cardiac tuberculosis manifesting as predominantly right‐sided cardiomyopathy. In addition to being a very rare clinical presentation, this case provided an interesting insight into the left ventricular (LV) myocardial mechanics. The patient had nearly preserved contractile function of the LV myocardium (except for segmental abnormalities in circumferential strain) but had marked impairment of torsion resulting in LV systolic dysfunction. Such disproportionate loss of LV torsion leading to LV systolic dysfunction has not been previously described on echocardiography. These myocardial mechanical abnormalities almost completely recovered with adequate antitubercular treatment. Thus, this case proved to be a unique demonstration of the significant, independent role played by torsion in maintenance of normal LV systolic function.
Incremental Value of Live/Real Time Three‐Dimensional Echocardiography in the Diagnosis and Evaluation of Pericardial Cyst
Authors: Pandey Abhilasha , Daly David D. , Sudhakar Selvin , Nanda Navin C. , Singh Satinder P. , Gokhroo Rahul , Sadat Kamel , Dumaswala Bhavin , Dumaswala Komal , Patel Adilahmed
Published: July 2012

Pericardial cysts are rare anomalies of the pericardium that are usually asymptomatic and followed by two‐dimensional (2D) echocardiography. Here we report a large pericardial cyst that could not be measured accurately by 2D echocardiography but three‐dimensional (3D) echocardiography enabled measurements of the cyst that correlated well with computed tomography measurements. In addition, 3D echocardiography demonstrated the mono‐trabeculated nature of the cyst further suggesting the incremental value of 3D echocardiography in the evaluation of pericardial cysts. The cyst was subsequently resected surgically.
Mitral Leaflet Perforation: A Rare Complication of Mitral Annular Calcification
Authors: Rengifo‐Moreno Pablo , Movva Rajesh , Tulenko Thomas D. , Pressman Gregg S.
Published: July 2012

A 42‐year‐old dialysis patient presented with congestive heart failure. A large, calcified mass on the posterior mitral leaflet with an opposing anterior leaflet perforation, and a diastolic jet extending into the left ventricular outflow tract was noted on Doppler echocardiography. The patient underwent mechanical mitral valve replacement and surgical specimen confirmed these findings with no evidence of endocarditis.
Right Atrial Thrombus as a Complication of Supraventricular Tachycardia Ablation Resolved by Anticoagulation
Authors: Pagourelias Efstathios D. , Fragakis Nikolaos , Rossios Konstantinos , Avramidou Athanasia , Geleris Paraschos
Published: July 2012

We present the case of a 40‐year‐old man who was found on routine echocardiography to have a right atrioventricular thrombus, 24 hours after succesful supraventricular trachycardia ablation he had undergone. With the patient being asymptomatic, coumarin anticoagulants were started, leading to complete clot resolution two weeks later. In this case, we stress the importance of routine echocardiography to identify thrombotic complications after ablation and we describe the course of a large right atrioventricular thrombus which was successfully treated with Vit K antagonists.
Economic growth and restructuring in Canada's heartland and hinterland: From shift‐share to multifactor partitioning
Authors: Ray D. Michael , Lamarche R. H. , Beaudin Maurice
Published: July 2012

The geography of the Canadian economy has long been dominated by heartland‐hinterland contrasts, with manufacturing identified as the dominant function of most heartland cities in analyses of the 1961 and 1971 census data. However, the proportion of employment in manufacturing has been declining in the heartland provinces of Ontario and Quebec over the past fifty years and some geographers argue that the heartland‐hinterland dimension of the regional economy is being overridden by city‐regions that are integrated into global networks of production and trade. The heartland‐hinterland trends are examined using multifactor partitioning (MFP), an advanced shift‐share methodology, for the period of 2001–2006. This is the first intercensal period in which Canadian business has faced the full impact of the removal of North American tariff protection and the increased globalization of the Canadian economy. The data covers employment by eighteen industry sectors for the seventy‐three economic regions defined by Statistics Canada. MFP measures the region and industry‐mix effects, which are interpreted as in the traditional shift‐share model (though they are derived more accurately) and, in addition, an interaction effect. The results demonstrate that the broad heartland‐hinterland differences in the distribution of population and employment growth are increasing not decreasing and that the hinterland is in fact falling further behind the heartland in employment growth. However the Calgary‐Edmonton corridor and the Lower Mainland of British Columbia are emerging as a western heartland. The population size of cities does affect their rates of employment growth, but so too does their location: the growth of heartland cities is outpacing those in the hinterland. The Appendix provides the equations for two‐variable multifactor partitioning.
Insular dysfunction and descending pain inhibition in anorexia nervosa
Authors: Bär K.‐J. , Berger S. , Schwier C. , Wutzler U. , Beissner F.
Published: July 2012

Objective:  Reduced perception of pain is a well‐established phenomenon in patients with anorexia nervosa (AN). We tested the hypothesis that altered processing of pain within the insula might account for reduced perception of pain.

Method:  Heat pain thresholds were obtained in nineteen patients with AN and matched controls. Thereafter, a thermode was used to deliver thermal painful stimuli to the right arm during functional magnetic resonance imaging (fMRI) measurements. Stimuli were initiated for 10 s from a baseline resting temperature (32°C) to three different levels (37, 42, 45°C).

Results:  Significantly increased heat pain thresholds were observed in patients. A stronger activation during heat pain perception was found in the left posterior insula in controls. In contrast, higher levels of activity were shown in the ipsilateral pons in patients when compared to controls. In patients, we found a significant interrelation between the depression score (Beck depression inventory) and heat pain activations.

Conclusion:  We suggest that reduced activity in the left posterior insula might contribute to increased pain thresholds in patients, while increased activations in the right anterior insula and pons mirror augmented sympathetic modulation putatively related to amplification of adrenergic descending pain inhibition. In addition, pain thresholds and brain activations were influenced by disease‐inherent depressed mood.
Specificity of grouping behaviour: comparing colony sizes for the same seabird species in distant populations
Authors: Jovani Roger , Schielzeth Holger , Mavor Roddy , Oro Daniel
Published: July 2012

Animal collective patterns such as group size frequency distributions often show substantial intraspecific variation, suggesting low species‐specific consistency. Here, we dissect intraspecific vs interspecific components of colony size variation to estimate the repeatability (R) of colony size frequency distribution (CSFD) statistics for seabird species breeding in at least two out of four distant geographic areas of the Northern Hemisphere (21 species; 57 populations; 21 665 colonies; 9 326 479 breeding pairs). Colony sizes were highly variable both within and between species. We estimated the proportion of between‐species variation using the repeatability statistic. Colony size‐related statistics of CSFDs (e.g. geometric mean) showed high repeatabilities (R= 0.73–0.88), and shape‐related measures ranged from null (kurtosis), moderate (fit to a log‐normal distribution,R= 0.62) to highly repeatable (e.g. skewness,R= 0.74–0.87). We thus show that species collective patterns can be at the same time highly variable within species and a robust species‐specific trait that bridge ecological spatio‐temporal heterogeneities.
Finding food in a highly seasonal landscape: where and how pink footed geese Anser brachyrhynchus forage during the Arctic spring
Authors: Anderson Helen B. , Godfrey Thomas G. , Woodin Sarah J. , van der Wal René
Published: July 2012

Food accessibility and availability in the highly seasonal Arctic landscape can be restricted by snow cover and frozen substrate, particularly in early spring. Therefore, to determine how a long distance migratory herbivore forages in such a landscape, pink‐footed geese Anser brachyrhynchus at an early spring feeding area in Svalbard were studied. Birds arrived in mid May when extensive snow cover restricted habitat availability. Geese fed in all habitats, but the highest densities occurred in wet tundra. However, prolonged snow lie restricted access to wet areas compared to dry and mesic habitats. Above ground biomass was very low in all habitats; yet sizeable amounts occurred below ground. In line with this, the majority of birds (86%) grubbed for below ground plant storage organs such as stem bases and rhizomes. Wet habitat contained greater quantities of edible and lower amounts of inedible below ground material (ratio 1:0.3) than dry (ratio 1:9) or mesic (ratio 1:4) areas. Although foraging in wet habitat prevented geese from encountering high proportions of inedible plant parts, forage species characteristic of this habitat, such as Dupontia grasses and the rush Eriophorum scheuchzeri, were more difficult to extract than food plants typical of drier habitats such as the forb Bistorta vivipara. Hence, we suggest that wet areas are preferred by pink‐footed geese, but the prolonged snow lie there made it necessary to use less preferred but much more abundant drier habitats, which experienced earlier snowmelt and indeed accommodated more than half of all goose foraging recordings.
Are allergenic disperse dyes used for dyeing textiles?
Authors: Malinauskiene Laura , Zimerson Erik , Bruze Magnus , Ryberg Kristina , Isaksson Marléne
Published: July 2012

Background. There are no data showing that disperse dyes, used to patch test patients, are currently being used for dyeing synthetic garments. It is unknown whether disperse dyes, which are currently routinely patch tested, are in fact present in synthetic textiles on the market.

Objectives. To determine whether eight disperse dyes, hitherto most widely cited as allergenic, are still used in textiles that are sold in various countries.

Methods. Textiles from 13 countries in Europe, Asia and the United States were analysed. The procedure used for dye identification was thin‐layer chromatography. When there were matching spots from the textile extract and reference dye, high‐performance liquid chromatography was performed.

Results. Of 121 analysed items, three showed positive results for some of the investigated disperse dyes. Four dyes in these items could be detected and confirmed by the use of high‐performance liquid chromatography. A pair of light brown ladies' tights manufactured and purchased in Italy contained Disperse Yellow 3, Disperse Blue 124, and Disperse Blue 106, and a set of black bra and panties purchased in India contained Disperse Orange 1.

Conclusions. The eight disperse dyes that are most frequently incriminated in textile dye dermatitis are very rarely used in textiles nowadays.
Nickel, chromium and cobalt sensitization in a patch test population in north‐eastern Italy (1996–2010)
Authors: Rui Francesca , Bovenzi Massimo , Prodi Andrea , Belloni Fortina Anna , Romano Ilaria , Corradin Maria Teresa , Larese Filon Francesca
Published: July 2012

Background. Sensitization to nickel, cobalt and chromium is frequent in patch test populations. The prevalence is affected by geographical and socio‐cultural factors.

Objectives. To investigate the temporal trend of nickel, cobalt and chromium contact sensitization between 1996 and 2010 in north‐eastern Italy.

Patients/methods. Nineteen thousand and eighty‐eight patients (67.2% women and 32.8% men) with suspected allergic dermatitis underwent patch testing with the European baseline series. The associations between nickel, cobalt and chromium sensitization and patient age (in quintiles) and year of patch testing were investigated by means of multivariate logistic regression analysis.

Results. The prevalence of nickel sensitization decreased significantly among younger women (≤26 years), from 38.3% (1996–1998) to 31.9% (2002–2004), 28.3% (2005–2007) and 29.0% (2008–2010), whereas an increase was observed in the 36–45‐year and 46–58‐year age groups. The overall prevalence of chromium sensitization dropped from 10.2% (1996–1998) to 4.6% (2008–2010) among women, and from 11.3% (1996–1998) to 5.9% (2008–2010) among men. The prevalence of cobalt sensitization increased among younger men (≤26 years), from 2.7% (1996–1998) to 7.3% (1999–2001), 9.6% (2002–2004), and 6.6% (2005–2007).

Conclusions. Our study showed a decreasing trend of nickel sensitization (only among younger women) and of chromium sensitization in both sexes.
Quantitative expression analysis of the apoptosis‐related gene, BCL2L12, in head and neck squamous cell carcinoma
Authors: Geomela Panagiota‐Aikaterini , Kontos Christos K. , Yiotakis Ioannis , Scorilas Andreas
Published: July 2012

J Oral Pathol Med (2013)42: 154–161

Background:  BCL2L12 is a recently identified gene belonging to the BCL2 family, members of which are implicated in head and neck squamous cell carcinoma (HNSCC). We have recently shown that BCL2L12 mRNA expression is an unfavorable prognostic indicator in nasopharyngeal carcinoma (NPC) and that BCL2L12 can be regarded as a novel, useful tissue biomarker for the prediction of NPC patients’ short‐term relapse. The aim of this study was to analyze the mRNA expression of the novel apoptosis‐related gene BCL2L12 in patients with HNSCC.

Methods:  Total RNA was isolated from 53 malignant tumors originating in larynx, pharynx, tongue, buccal mucosa, parotid glands, and nasal cavity, as well as from 34 adjacent non‐cancerous tissue specimens, resected from patients with HNSCC. A highly sensitive real‐time PCR method for BCL2L12 mRNA quantification in head and neck tissues was developed using the SYBR® Green chemistry. After preparing cDNA by reverse transcription, relative quantification was performed using the comparative CT () method.

Results:  BCL2L12 mRNA levels were lower in laryngeal tumors of advanced tumor, node, metastasis (TNM) stage or bigger size and in well‐differentiated malignant tongue neoplasms, compared with early‐stage laryngeal tumors or poorly differentiated tongue tumors. Interestingly, the BCL2L12 expression showed significant discriminatory value, distinguishing efficiently patients with tongue squamous cell carcinoma (SCC) from non‐cancerous population.

Conclusions:  This is the first study examining the BCL2L12 mRNA expression in HNSCC. Our results suggest that BCL2L12 mRNA expression may serve as a potential prognostic biomarker in tongue and/or larynx SCC, which principally constitute the great majority of HNSCC cases worldwide.
Influence of surface charge of gold nanorods on skin penetration
Authors: Lee Onseok , Jeong Sang Hoon , Shin Won Ung , Lee Gunwoo , Oh Chilhwan , Son Sang Wook
Published: July 2012

Background/purpose

The skin plays an important role as a protective barrier against toxic environments and also is a route of drug administration. In spite of evidence for and interest in the skin penetration of nanoparticles, no study has examined the effect of nanoparticle surface charge on percutaneous absorption. In this study, we investigated the effect of surface charges of gold nanorods (GNs) on skin penetration.

Methods

Using transmission electron microscopy (TEM) and image analysis, we quantitatively measured the ability of GNs to penetrate the skin.

Results

Our results showed that the area density of the electron‐dense dots of GNs, which penetrated into the stratum corneum, significantly increased for negatively charged GNs compared to those with a positive charge (P < 0.01). To investigate the percutanoues absorption of charged GNs, in vitro skin permeation studies were carried out using a Franz‐type diffusion cell (FDC). The penetration of GNs through the skin was quantified by inductively coupled plasma mass spectrometry. Consistent with TEM observations, our penetration study using an FDC also revealed that negative particles were frequently detected in samples of receptor fluid at 48 h after exposure (P < 0.01).

Conclusion

Together our results showed that anionic GNs penetrate skin better than cationic GNs.
Termination of Isoform‐Selective Vps21/Rab5 Signaling at Endolysosomal Organelles by Msb3/Gyp3
Authors: Nickerson Daniel P. , Russell Matthew R. G. , Lo Shing‐Yeng , Chapin Hannah C. , Milnes Joshua M. , Merz Alexey J.
Published: July 2012

Traffic through endosomes and lysosomes is controlled by small G‐proteins of the Rab5 and Rab7 families. Like humans, Saccharomyces cerevisiae has three Rab5s (Vps21, Ypt52 and Ypt53) and one Rab7 (Ypt7). Here, we elucidate the functional roles and regulation of the yeast Rab5s. Using GFP‐tagged cargoes, a novel quantitative multivesicular body (MVB) sorting assay, and electron microscopy, we show that MVB biogenesis and thus MVB cargo sorting is severely impaired in vps21Δ ypt52Δ double mutants. Ypt53, the third Rab5 paralog, is hardly expressed during normal growth but its transcription is strongly induced by cellular stress through the calcineurin‐Crz1 pathway. The requirement for Rab5 activity in stress tolerance facilitated identification of Msb3/Gyp3 as the principal Rab5 GAP (GTPase accelerating protein). In vitro GAP assays verified that Vps21 is a preferred Gyp3 target. Moreover, we demonstrate that Gyp3 spatially restricts active Vps21 to intermediate endosomal compartments by preventing Vps21 accumulation on lysosomal vacuoles. Gyp3, therefore, operates as a compartmental insulator that helps to define the spatial domain of Vps21 signaling in the endolysosomal pathway.
Linkage analysis confirms heterogeneity of hereditary gingival fibromatosis
Authors: Nibali L , Medlar A , Stanescu H , Kleta R , Darbar U , Donos N
Published: July 2012

Objectives

Hereditary Gingival Fibromatosis (HGF) is a rare benign fibrous lesion of the gingival tissues presumably caused by single gene defects. The aim of this study was to identify the genetic defect leading to HGF in an extended pedigree.

Materials and Methods

We report the clinical features and genetic analysis of a family affected by HGF. A total of 17 subjects were assessed clinically and had blood samples taken for DNA extraction. Multipoint parametric linkage analysis was performed to identify the possible chromosomal location responsible for HGF in this family.

Results

Presence of severe HGF associated with tooth impaction was confirmed for seven members of this three‐generation family. Linkage analysis revealed that loci on chromosomes 7, 10, 13, 15, 16, 17, 19 and 20 were linked to this trait. Previously found mutations in the SOS1 and GINGF loci were therefore excluded by this analysis.

Conclusions

This study brings further evidence for genetic heterogeneity of HGF and points towards the existence of different, not‐yet‐identified genes linked to this condition.
The growth and osteoclastogenic effects of fibroblasts isolated from keratocystic odontogenic tumor
Authors: Wang H‐C , Li T‐J
Published: July 2012

Oral Diseases (2012)

Objectives:  To investigate the growth characteristics and effects on osteoclastogenesis in fibroblasts isolated from keratocystic odontogenic tumor (KCOT) fibrous capsule.

Materials and Methods:  Fibroblasts isolated from KCOT fibrous capsule and normal gingival mucosa were cultured in vitro. Their colony‐forming units and proliferative activity were investigated, and the osteoclastogenic effects were also observed by a co‐culture system with osteoclast precursor cell line Raw264.7. The mRNA of several genes related to bone resorption (IL‐6, VEGF, COX‐2, and M‐CSF) was analyzed by real‐time PCR.

Results:  Keratocystic odontogenic tumor fibroblasts developed fewer CFU and had longer population doubling time than gingival fibroblasts (P < 0.05). In contrast to gingival fibroblasts, KCOT fibroblasts expressed less IL‐6, COX‐2, and M‐CSF (P < 0.05); however, the Raw264.7 co‐cultured with KCOT fibroblasts developed more osteoclast‐like cells and expressed higher level of nfatc1 than that co‐cultured with gingival fibroblasts. Increased COX‐2 expression and VEGF expression were detected in KCOT fibroblasts and Raw264.7 co‐culture system (P < 0.05).

Conclusion:  Although KCOT fibroblasts showed lower level of cell proliferation than gingival fibroblasts, higher osteoclastogenic ability was detected when co‐cultured with Raw264.7. These results suggest that the cell–cell interaction in the co‐culture system, possibly by increasing COX‐2 and VEGF expression, may be responsible for the increased osteoclastogenic effects of KCOT fibroblasts.
“Smoking guns”: Hazards generated by laser and electrocautery smoke
Authors: Karsai Syrus , Däschlein Georg
Published: July 2012

The smoke generated by laser surgery and electrocautery may contain significant amounts of toxic, carcinogenic, and infectious gases and particles. Although there is little scientific data on the actual type and extent of the hazards related to exposure, considering the potential for irreversible health damage, safety measures should not be delayed. All potentially exposed persons (including patients, medical, and cleaning staff) should be acquainted with the possible health and occupational hazards related to smoke from electrocautery and laser surgery procedures.
Postnatal percentile growth charts for Indian appropriate for gestational age (AGA) very low birth weight babies
Authors: Kumar Sarath , Bhalla Anil Kumar , Mukhopadhyay Kanya , Narang Anil
Published: July 2012

Aims:  To develop postnatal percentile growth charts for Indian very low birth weight (VLBW) appropriate for gestational age (AGA) babies till 37 weeks post conceptional age (PCA).

Methods:  Prospective, mixed longitudinal study in 105 VLBW AGA (male 73 and female 32) babies weighing <1500 g and <34 weeks gestation born over 1 year. All were weighed daily until discharge and then weekly till 37 weeks of PCA. The percentile weight curves were computed in four categories : ≤28 weeks, 29–30, 31–32 and 33 weeks, and a total of seven percentile distributions (3rd, 10th, 25th, 50th, 75th, 90th& 97th) were generated. Entire data were subjected to Tanner’s 1951 method to compute mean and standard deviation for body weight. The arithmetic mean served the 50th percentile.

Results:  All babies at birth were <50th centile as per Lubchenco’s intrauterine growth chart. This pattern was more evident in higher gestation (31–32 and 33 weeks) than lower gestation (≤28 and 29–30 weeks). At 37 weeks PCA, all were <10th centile and the lowest was in ≤28 weeks gestation.

Conclusions:  Our babies are born smaller, and growth rate is slower than their western counterparts. Babies at lowest gestation had slowest postnatal growth. Hence, we need a separate growth chart for our babies.
Local plant species delimitation in a highly diverse Amazonian forest: do we all see the same species?
Authors: Gomes Ana C.S. , Andrade Ana , Barreto‐Silva Juan S. , Brenes‐Arguedas Tania , López Dairon C. , de Freitas Camila C. , Lang Carla , de Oliveira Alexandre A. , Pérez Alvaro J. , Perez Rolando , da Silva João B. , Silveira Alexandra M.F. , Vaz Marcel C. , Vendrami Juliana , Vicentini Alberto
Published: July 2012

Question

How reliable is the process of delimiting plant species by morphotyping sterile specimens from a highly diverse Amazonian forest plot?

Location

Biological Dynamics of Forest Fragments Project (BDFFP), Central Amazon, Manaus, Brazil.

Methods

A taxonomic exercise was conducted during a Center for Tropical Forest Science (CTFS) Taxonomy Workshop held in Manaus in April 2011, using specimens collected in a 25‐ha forest plot. The plant species from this plot had been previously delimited by morphotyping of ca. 80 000 sterile specimens, a process that resulted in the recognition of 115 cases (accounting for 38% of all trees) in which species delimitation was problematic. For the workshop, we selected a subsample of specimens for eight of these difficult cases (taxonomic groups/complexes) and asked 14 participants with different levels of botanical training to independently sort these specimens into morphospecies. We then compared the classifications made by all participants and explored correlations between botanical training and plant classification.

Results

The classification of specimens into morphospecies was highly variable among participants, except for one taxonomic group/complex, for which the median pair‐wise similarity was 95%. For the other seven taxonomic groups/complexes, median pair‐wise similarity values ranged from 52% to 67%. Training did not increase the similarity in the definition of morphospecies except for two taxonomic groups/complexes, for which there was higher congruence between the classifications made by participants with a high level of botanical training than in comparisons that included less‐experienced participants. The total number of morphospecies defined by participants was highly variable for all taxonomic groups/complexes, with the total number varying from 12 to 46 (a 383% difference).

Conclusions

Local plant species delimitation by morphotyping sterile specimens is prone to large uncertainties, and botanical training may not reduce them. We argue that uncertainty in species delimitation should be explicitly considered in plant biodiversity inventories as diversity estimates may be strongly affected by such uncertainties. We recommend that species delimitation and identification be treated as separate processes and that difficulties be explicitly recorded, so as to permit error estimates and the refinement of taxonomic data.
Partitioning the variation of woody plant β‐diversity in a landscape of secondary tropical dry forests across spatial scales
Authors: López‐Martínez J.O. , Hernández‐Stefanoni J.L. , Dupuy J.M. , Meave J.A.
Published: July 2012

Question

What is the relative importance of forest successional age, environmental heterogeneity, landscape structure and spatial structure of sampling sites on β‐diversity of tropical dry forests (TDF)? How do the magnitude of β‐diversity and the relative influence of factors, processes and mechanisms driving β‐diversity differ at different spatial grains? What are the effects of stand age on β‐diversity?

Location

Yucatán Peninsula, México.

Methods

Floristic composition was obtained from a hierarchical survey performed in 276 sites distributed across 23 sampling landscapes (SL) (12 sites per SL). Land‐cover classes were derived from the classification of multi‐spectral SPOT 5 satellite imagery. We calculated landscape metrics of patch type for each SL, and characterized local soil conditions for each sampling site. A principal coordinates of neighbour matrices (PCNM) analysis was performed to estimate spatial variables, and partial redundancy analysis was used to decompose variation into spatial, stand age and landscape structure components.

Results

The magnitude of β‐diversity varied with spatial scale (grain size), and was larger at the local than at the landscape grain. The magnitude of β‐diversity also decreased slightly but significantly with successional age. There were significant differences in species composition among vegetation classes. Environmental factors (local soil conditions, as well as landscape structure) and spatial structure both contributed to woody plant β‐diversity in our TDF landscape, but their relative importance was scale‐dependent. At the local grain size, both the environment (mainly soil conditions) and the spatial structure strongly affected β‐diversity, while at the landscape grain, environmental factors (variation in soil conditions, as well as landscape configuration) played a more prominent role.

Conclusions

The magnitude of β‐diversity decreased with increasing spatial grain and successional age, while the relative importance of mechanisms influencing β‐diversity was scale‐dependent: both niche partitioning and dispersal limitation affect β‐diversity at the local grain size, while niche partitioning prevails at the landscape grain.
The Incarnation and Jesus’ Apparent Limitation in Knowledge
Authors: Loke Andrew
Published: July 2012

One of the problems confronting the doctrine of the Incarnation concerns Jesus’ apparent limitation in knowledge. This paper assesses various constructive proposals by modern theologians and philosophers, focusing on three of the most widely discussed solutions, namely Ontological Kenoticism, Two Consciousnesses Model, and Divine Subconscious Model. I argue that despite recent work done on the first two, the difficulties of avoiding the implication that the Logos ceased to be divine (for the first) and the implication of Nestorianism (for the second) remain. I conclude that the most promising solution is to defend Functional Kenoticism and develop the Divine Subconscious Model.
SIRPα interacts with nephrin at the podocyte slit diaphragm
Authors: Kajiho Yuko , Harita Yutaka , Kurihara Hidetake , Horita Shigeru , Matsunaga Atsuko , Tsurumi Haruko , Kanda Shoichiro , Sugawara Noriko , Miura Kenichiro , Sekine Takashi , Hattori Seisuke , Hattori Motoshi , Igarashi Takashi
Published: July 2012

The slit diaphragm (SD) is an intercellular junction between renal glomerular epithelial cells (podocytes) that is essential for permselectivity in glomerular ultrafiltration. The SD components, nephrin and Neph1, assemble a signaling complex in a tyrosine phosphorylation dependent manner, and regulate the unique actin cytoskeleton of podocytes. Mutations in the NPHS1 gene that encodes nephrin cause congenital nephrotic syndrome (CNS), which is characterized by the loss of the SD and massive proteinuria. Recently, we have identified the expression of the transmembrane glycoprotein signal regulatory protein α (SIRPα) at the SD. In the present study, we analyzed the expression of SIRPα in developing kidneys, in kidneys from CNS patients and in proteinuric rat models. The possibility that SIRPα interacts with known SD proteins was also investigated. SIRPα was concentrated at the SD junction during the maturation of intercellular junctions. In the glomeruli of CNS patients carrying mutations in NPHS1, where SD formation is disrupted, the expression of SIRPα as well as Neph1 and nephrin was significantly decreased, indicating that SIRPα is closely associated with the nephrin complex. Indeed, SIRPα formed hetero‐oligomers with nephrin in cultured cells and in glomeruli. Furthermore, the cytoplasmic domain of SIRPα was highly phosphorylated in normal glomeruli, and its phosphorylation was dramatically decreased upon podocyte injury in vivo. Thus, SIRPα interacts with nephrin at the SD, and its phosphorylation is dynamically regulated in proteinuric states. Our data provide new molecular insights into the phosphorylation events triggered by podocyte injury.

Structured digital abstract

 Sirp‐alpha physically interacts with Nephrin by anti bait coimmunoprecipitation (View interaction)

 Sirp‐alpha physically interacts with Nephrin by anti tag coimmunoprecipitation (View interaction)
Production and characterization of scFvA33T1, an immunoRNase targeting colon cancer cells
Authors: Tomé‐Amat Jaime , Menéndez‐Méndez Aida , García‐Ortega Lucía , Batt Carl A. , Oñaderra Mercedes , Martínez‐del‐Pozo Álvaro , Gavilanes José G. , Lacadena Javier
Published: July 2012

Within the last 10 years, the use of different RNases as therapeutic agents for various diseases has been pursued. Furthermore, the advancements of recombinant technology have allowed the assembly of proteins with different functions. In this regard, immunoribonucleases (immunoRNases) stand out as some of the most promising therapeutic candidates given their enzymatic and non‐mutagenic character. Accordingly, the work reported here describes fusing RNase T1, one of the most studied members of the microbial RNase family, to the single‐chain variable fragment (scFv) of a monoclonal antibody that targets the glycoprotein A33 antigen (GPA33) from human colon cancer cells. A heterologous production system, which employs the yeast Pichia pastoris, has been optimized to produce this immunoRNase (scFvA33T1) with yields of ∼ 5–10 mg·L−1. The purified protein appears to be correctly folded as it retains its antigen specificity and ribonucleolytic activity. Finally, it also shows specific binding to, internalization into and toxicity against GPA33‐positive cell lines compared with the control, GPA33‐negative cells. Overall, it can be concluded that scFvA33T1 is a promising therapeutic fusion protein with the additional advantage that presumably it can be produced and purified in large amounts using an easily scalable yeast‐based system.
Lens epithelium‐derived growth factor deSumoylation by Sumo‐specific protease‐1 regulates its transcriptional activation of small heat shock protein and the cellular response
Authors: Ishihara Keiichi , Fatma Nigar , Bhargavan Biju , Chhunchha Bhavana , Kubo Eri , Dey Sanjib , Takamura Yoshihiro , Kumar Anil , Singh Dhirendra P.
Published: July 2012

Lens epithelium‐derived growth factor (LEDGF), a ubiquitously expressed nuclear protein, acts by interacting with DNA and protein and is involved in widely varying cellular functions. Despite its importance, the mechanism(s) that regulate naturally occurring LEDGF activity are unidentified. In the present study, we report that LEDGF is constitutively Sumoylated, and that the dynamical regulatory mechanism(s) (i.e. Sumoylation and deSumoylation) act as a molecular switch in modulating the DNA‐binding and transcriptional activity of LEDGF with the functional consequences. Using bioinformatics analysis coupled with in vitro and in vivo Sumoylation assays, we found that lysine (K) 364 of LEDGF was Sumoylated, repressing its transcriptional activity. Conversely, mutation of K364 to arginine (R) or deSumoylation by small ubiquitin‐like modifier (Sumo)‐specific protease‐1, a nuclear deSumoylase, enhanced the transactivation capacity of LEDGF and its cellular abundance. The enhancements were directly correlated with an increase in the DNA‐binding activity and small heat shock protein transcription of LEDGF, whereas the process was reversed in cells overexpressing Sumo1. Interestingly, cells expressing Sumoylation‐deficient pEGFP‐K364R protein showed increased cellular survival compared to wild‐type LEDGF protein. The findings provide insights into the regulation and regulatory functions of LEDGF in Sumoylation‐dependent transcriptional control that may be essential for modifying the physiology of cells to maintain cellular homeostasis. These studies also provide new evidence of the important role of post‐translational modification in controlling LEDGF function.

Structured digital abstract

 LEDGF and SUMO1 colocalize by fluorescence microscopy (View interaction)

 LEDGFphysically interacts with SUMO1 by anti bait coimmunoprecipitation (View Interaction: 1, 2, 3)
Structure and stability of a thermostable carboxylesterase from the thermoacidophilic archaeon Sulfolobus tokodaii
Authors: Angkawidjaja Clement , Koga Yuichi , Takano Kazufumi , Kanaya Shigenori
Published: July 2012

The hormone‐sensitive lipase (HSL) family is comprised of carboxylesterases and lipases with similarity to mammalian HSL. Thermophilic enzymes of this family have a high potential for use in biocatalysis. We prepared and crystallized a carboxylesterase of the HSL family from Sulfolobus tokodaii (Sto‐Est), and determined its structures in the presence and absence of an inhibitor. Sto‐Est forms a dimer in solution and the crystal structure suggests the presence of a stable biological dimer. We identified a residue close to the dimer interface, R267, which is conserved in archaeal enzymes of HSL family and is in close proximity to the same residue from the other monomer. Mutations of R267 to Glu, Gly and Lys were conducted and the resultant R267 mutants were characterized and crystallized. The structures of R267E, R267G and R267K are highly similar to that of Sto‐Est with only slight differences in atomic coordinates. The dimerized states of R267E and R267G are unstable under denaturing conditions or at high temperature, as shown by a urea‐induced dimer dissociation experiment and molecular dynamics simulation. R267E is the most unstable mutant protein, followed by R267G and R267K, as shown by the thermal denaturation curve and optimum temperature for activity. From the data, we discuss the importance of R267 in maintaining the dimer integrity of Sto‐Est.

Database

The atomic coordinates and structural factors have been deposited in the Protein Data Bank with accession numbers of PDB: 3AIK for noninhibited Sto‐Est, PDB: 3AIL for DEP‐bound, PDB: 3AIM for R267E, PDB: 3AIN for R267G, and PDB: 3AIO for R267K

Structured digital abstract

 Sto‐Es and Sto‐Es bind by comigration in gel electrophoresis (View Interaction: 1, 2)

 Sto‐Es and Sto‐Es bind by x‐ray crystallography (View interaction)