bluuebunny/crossref_metadata_2025 huggingface dataset:
A critical role of TRAIL expressed on cotransplanted hepatic stellate cells in prevention of islet allograft rejection
Authors: Yang Horng‐Ren , Hsieh Ching‐Chuan , Wang Lianfu , Fung John J. , Lu Lina , Qian Shiguang
Published: September 2009

Hepatic stellate cells (HSCs) have demonstrated a strong T‐cell inhibitory activity. In a mouse islet transplantation model, cotransplanted HSCs can protect islet allografts from rejection. The involved mechanism is not fully understood. We showed in this study that expression of tumor necrosis factor‐related apoptosis‐inducing ligand (TRAIL), an important apoptosis‐inducing ligand, on HSCs was crucial in protection of islet allografts, since HSCs derived from TRAIL knockout mice demonstrated less inhibitory activity towards T‐cell proliferative responses, and substantially lost their capacity in protecting cotransplanted islet allografts from rejection, suggesting that TRAIL‐mediated T cell apoptotic death is important in HSC‐delivered immune regulation activity. © 2009 Wiley‐Liss, Inc. Microsurgery 2010.
Use of the descending branch of lateral circumflex femoral artery as a recipient pedicle for coverage of a knee defect with free flap: Anatomical and clinical study
Authors: Kim Jun Sik , Lee Hyung Suk , Jang Pal Young , Choi Tae Hyun , Lee Kyung Suk , Kim Nam Gyun
Published: September 2009

Background:

With recent advances in free tissue transfer, soft tissue defects involving the knee can be covered perfectly utilizing various free flaps. Yet the success of this operation depends on a secure nontraumatic recipient pedicle around the knee area. The purpose of this study is to introduce the descending branch (DB) of the lateral circumflex femoral artery (LCFA) as a new recipient pedicle for knee defect coverage.

Methods:

Through autopsies of eight cadavers and a total of 11 extremities involving the area 10‐ and 15‐cm above the upper margin of the patella, the number and sizes of the artery and vein of the descending branch of the lateral circumflex femoral artery were investigated. In a clinical setting, two cases of soft tissue defects in the area of the knee were reconstructed utilizing the DB of the LCFA with an anterolateral thigh perforator (ALTP) free flap on the ipsilateral side.

Results:

Anatomical: The descending branches of the lateral circumflex femoral vessels measuring 10‐ and 15‐cm above the lateral aspect of the patella numbered 1 artery and about 1.5 veins. The diameters of these vessels ranged from 1.0 to 2.0 mm (1.4 ± 0.4 mm) for the artery at 10‐cm site and 1.0 to 3.0 mm (1.9 ± 0.5 mm) at the 15‐cm site and 0.8 to 2.0 mm (1.2 ± 0.4 mm) for the vein at the 10‐cm site and 1.0 to 3.0 mm (1.9 ± 0.5 mm) at the 15‐cm site. Under clinical conditions, the two case flaps survived well without major complications. The clinical follow‐up period was from 12 to 14 months (mean: 13 months).

Conclusions:

The advantage in using this recipient pedicle lies not only in its superficial aspect but also in the protection offered by the surrounding muscle. Thus the defect could be reconstructed efficiently without stress upon the surgeon; if the ALTP flap of the ipsilateral side was used, the defect could be reconstructed efficiently within the same surgical field. © 2009 Wiley‐Liss, Inc. Microsurgery 2010.
Autism in children and adolescents with cancer
Authors: Blatt Julie , Deal Allison M. , Mesibov Gary
Published: September 2009

Background

The causes of autistic disorders (AD) are not known. Abnormalities of tumor suppressor genes have suggested that these genes may be important to the development of autism in some cases, and result in an increased risk of developing cancer or other neoplasms. We explore possible associations between AD and childhood cancer.

Procedure

We reviewed our institutional pediatric cancer database for all new cancer diagnoses 1997–2007. Medical records from patients older than 2 years at last visit were reviewed for a diagnosis of AD. The prevalence of AD was estimated for neoplasms overall and for specific tumor types, and compared with that in the general pediatric population.

Results

Of 702 eligible patients, 7 (1%; 95% CI: (0.4%, 2.04%)) were labeled as AD, not different than the prevalence of AD in North Carolina's general population (0.65%, P = 0.35). Cancer diagnoses for these 7 children were acute lymphoblastic leukemia (n = 1), acute nonlymphocytic leukemia (n = 2), non‐Hodgkin lymphoma (n = 1), Hodgkin Disease (n = 1), brain tumor (n = 1), osteogenic sarcoma (n = 1).

Conclusions

These data do not suggest that there is a high concordance between AD and childhood cancer. However, studies of large rigorously characterized AD cohorts will be needed to definitively address this issue. Pediatr Blood Cancer 2010; 54:144–147. © 2009 Wiley‐Liss, Inc.
Clinical and molecular characterization of S1118F‐CFTR
Authors: Penmatsa Himabindu , Frederick Carla A. , Nekkalapu Sunitha , Conoley Veronica G. , Zhang Weiqiang , Li Chunying , Kappes John , Stokes Dennis C. , Naren Anjaparavanda P.
Published: September 2009

Background

Cystic fibrosis is a lethal autosomal recessive disorder usually associated with lung disease, pancreatic insufficiency and high sweat chloride levels.

Clinical Case

A patient admitted to Le Bonheur Children's Medical Center (LBCMC, Memphis, TN) showed symptoms of meconium ileus which required exploratory laparotomy, bowel resection and ileostomy. Genotyping showed ΔF508/I1027T on one chromosome and S1118F on the other. Sweat testing on three different occasions gave negative and intermediate results (22.7, 24.6 mmol/L; 55.1, 58.6 mmol/L and 55.1, 58 mmol/L) and pancreatic elastase testing showed normal levels.

Objective

To characterize S1118F‐CFTR mutation at a molecular level to help understand the associated CF‐phenotype.

Methods

Molecular characterization of S1118F‐CFTR mutant was studied in HEK‐293 cells at 37°C. Various biochemical methods such as Western blotting, real‐time PCR, Pulse chase labeling and iodide efflux assay were employed.

Results

S1118F‐CFTR makes less than 10–15% of mature CFTR (band C) compared to WT‐CFTR. The mRNA levels of S1118F‐CFTR and WT‐CFTR are comparable. S1118F‐CFTR is functional but shows about 10–15% of WT‐CFTR activity. S1118F‐CFTR shows impaired maturation and CF‐correctors can increase the amount of mature and functional CFTR by three‐ to fourfold.

Conclusion

S1118F‐CFTR shows impaired maturation and an individual with S1118F‐CFTR paired with ΔF508‐CFTR exhibits atypical CF symptoms with intermediate sweat chloride level and meconium ileus despite documented pancreatic sufficiency. Pediatr Pulmonol. 2009; 44:1003–1009. ©2009 Wiley‐Liss, Inc.
Hydrogen bond of radicals: Interaction of HNO with HCO, HNO, and HOO
Authors: Yang Yong , Liu Ying
Published: September 2009

Ab initio quantum mechanics methods are employed to investigate hydrogen bonding interactions between HNO and HCO, HOO radicals, and closed‐shell HNO. The systems were calculated at MP2/6‐311++G (2d, 2p) level and G2MP2 level. The topological and NBO analysis were investigated the origin of hydrogen bonds red‐ or blue‐shifts. In addition, the comparisons were performed between HNO‐opened‐shell radical (HCO, HOO) complexes and HNO‐corresponding closed‐shell molecule (H2CO, HOOH) complexes. It is found that the stabilities of complexes increase from HNO‐HCO to HNO‐HOO. There are blue‐shifts of NH, CH stretching vibrational frequencies and a red‐shift of OH stretching vibrational frequency in the complexes. Rehybridization and electron density redistribution contribute to the blue‐shifts of CH and NH stretching vibrational frequencies. Compared with the closed‐shell H2CO, HCO is weaker proton donor and weaker proton acceptor. For the HOO, it is stronger proton donor and weaker proton acceptor than the HOOH is. © 2009 Wiley Periodicals, Inc. Int J Quantum Chem, 2010
Geometrical structures, electronic states, and stability of NinAl clusters
Authors: Wen Jun‐Qing , Jiang Zhen‐Yi , Li Jun‐Qian , Cao Li‐Ke , Chu San‐Yan
Published: September 2009

Density‐functional with generalized gradient approximation (GGA) for the exchange‐correlation potential has been used to calculate the energetically global‐minimum geometries and electronic states of NinAl (n = 2–8) neutral clusters. Our calculations predict the existence of a number of previously unknown isomers. All structures may be derived from a substitution of a Ni atom at marginal positions by an Al atom in the Nin+1 cluster. Aluminum atom remains on the surface of the geometrical configurations. Moreover, these species prefer to adopt three‐dimensional (3D) spacial forms at the smaller number of nickel atoms compared with the pure Nin+1 (n ≥ 3) configuration. Atomization energies per atom for NinAl (n = 2–8) have the same trend as the binding energies per atom for Nin (n = 3–9). The stabilization energies reveal that Ni5Al is the relatively most stable in this series. In comparison with the magnetic moment of pure metal nickel (0.6 μB), the average magnetic moment of Ni atom increases in NiAl clusters except the Ni3Al. Moreover, except the case of Ni5Al, Ni average magnetic moment decreases when alloyed with Al atoms than that in pure Ni clusters, which originate the effective charge transferring from Al to Ni atoms. © 2009 Wiley Periodicals, Inc. Int J Quantum Chem, 2010
Transfer of electron density as a result of hydrogen bond formation— A case of charged complexes
Authors: Sadlej‐Sosnowska N.
Published: September 2009

Previous investigation of transfer of electron density accompanying hydrogen bond formation has been extended to complexes between positively charged donors and neutral acceptors, as well as to the complexes between a neutral donor and a negatively charged acceptor molecules. The amount of transferred electron density from acceptor to donor for the charged complexes may be adequately described by the same exponential dependence on the equilibrium distance between the hydrogen atom and the nearest atom of the acceptor molecule as it was found for neutral complexes. Relation of the H‐bond energy to electron density at the H‐bond critical point was dependent on the sign of Laplacian of the electron density. © 2009 Wiley Periodicals, Inc. Int J Quantum Chem, 2010
Density functional study on electronic structures and reactivity in methyl‐substituted chelates used in organic light‐emitting diodes
Authors: Núñez‐Zarur Francisco , Arguello Eduardo , Vivas‐Reyes Ricardo
Published: September 2009

The electronic structure and reactivity trends of a set of tris‐(n‐methyl‐8‐quinolinolato) metal (III) (n = 0, 3, 4, 5; metal = Al+3, Ga+3) used as electron‐transport layer in organic light‐emitting diodes were studied and compared. All geometries were optimized at B3LYP/6‐31G(d,p) level of theory. The geometries of the ground state (S0) of unsubstituted molecules AlQ3 and GaQ3 were found to be slightly affected by the methyl group, which is in agreement with previous works. Methyl‐derivatives conserve largely the electronic structures of AlQ3 and GaQ3. The energies of the frontier orbitals highest occupied and lowest unoccupied molecular orbital are raised by the electron‐releasing effect of methyl group. Molecular orbital contribution analysis reveals that the orbital population is essentially the same for both MQ3 and their derivatives. Analyses of the ionization potential and electron affinity showed that MQ3 tend to be better hole‐blockers than methylated analogues and 5Me‐MQ3 have higher hole‐injection capability than the other methyl‐substituted derivatives. The global reactivity analysis showed that the electrophilicity index can be an indicator of electron‐injection capability in these complexes. Local reactivity analysis showed that atomic sites that are prone to nucleophilic/electrophilic attack are atoms C‐4 in L3/C‐5 in L1. © 2009 Wiley Periodicals, Inc. Int J Quantum Chem, 2010
Yap4 PKA‐ and GSK3‐dependent phosphorylation affects its stability but not its nuclear localization
Authors: Pereira Jorge , Pimentel Catarina , Amaral Catarina , Menezes Regina A. , Rodrigues‐Pousada Claudina
Published: September 2009

Yap4 is a nuclear‐resident transcription factor induced in Saccharomyces cerevisiae when exposed to several stress conditions, which include mild hyperosmotic and oxidative stress, temperature shift or metal exposure. This protein is also phosphorylated. Here we report that this modification is driven by PKA and GSK3. In order to ascertain whether Yap4 is directly or indirectly phosphorylated by PKA, we searched for stress and PKA‐related kinases that could phosphorylate Yap4. We show that phosphorylation is independent of the kinases Rim15, Yak1, Sch9, Slt2, Ste20 and Ptk2. In addition, we showed that Yap4 phosphorylation is also abrogated in the triple GSK3 mutant mck1 rim11 yol128c. Furthermore, our data reveal that Yap4 nuclear localization is independent of its phosphorylation state. This protein has several putative phosphorylation sites, but only the mutation of residues T192 and S196 impairs its phosphorylation under different stress conditions. The ability of the non‐phosphorylated forms of Yap4 to partially rescue the hog1 severe sensitivity phenotype is not affected, suggesting that Yap4 activity is maintained in the absence of phosphorylation. However, this modification seems to be required for stability of the protein, as the non‐phosphorylated form has a shorter half‐life than the phosphorylated one. Copyright © 2009 John Wiley & Sons, Ltd.
RRD1, a component of the TORC1 signalling pathway, affects anaesthetic response in Saccharomyces cerevisiae
Authors: Palmer Laura K. , Baptiste Beverly A. , Fester John C. , Perkins Justin C. , Keil Ralph L.
Published: September 2009

The molecular mechanisms of action of volatile anaesthetics remain unknown despite clinical use for over 150 years. While many effects of these agents have been characterized, clear insight into how these effects relate to the physiological state of anaesthesia has not been established. Volatile anaesthetics arrest cell division in Saccharomyces cerevisiae in a manner that parallels the anaesthetic actions of these drugs in mammals. To gain additional insight into the cellular activities of these drugs, we isolated genes that, when present on multi‐copy plasmids, render S. cerevisiae resistant to the volatile anaesthetic isoflurane. One of these genes, RRD1, encodes a subunit of the Tap42p–Sit4p–Rrd1p phosphatase complex that functions in the target of rapamycin complex 1 (TORC1) signalling pathway. In addition, we show that mutations in two other genes encoding components of the TORC1 pathway, GLN3 and URE2, also affect yeast anaesthetic response. These findings suggest that TORC1‐mediated signalling is involved in cellular response to volatile anaesthetics in S. cerevisiae. Copyright © 2009 John Wiley & Sons, Ltd.
How Do We Predict the Clinically Relevant Pancreatic Fistula After Pancreaticoduodenectomy?—An Analysis in 244 Consecutive Patients
Authors: Kawai Manabu , Tani Masaji , Hirono Seiko , Ina Shinomi , Miyazawa Motoki , Yamaue Hiroki
Published: September 2009

Background

The most important problem in pancreatic fistula is whether one can distinguish clinical pancreatic fistula, grade B + C fistula by the International Study Group on Pancreatic Fistula (ISGPF), from transient pancreatic fistula (grade A), in the early period after pancreaticoduodenectomy (PD). It remains unclear what predictive risk factors can precisely predict which clinical relevant or transient pancreatic fistula when diagnosed pancreatic fistula on POD3 by ISGPF criteria.

Methods

We analyzed the predictive factors of clinical pancreatic fistula by logistic regression analysis in 244 consecutive patients who underwent PD. Pancreatic fistula was classified into three categories by ISGPF.

Results

The rate of pancreatic fistula was 69 of 244 consecutive patients (28%) who underwent PD. Of these, 47 (19%) had grade A by ISGPF criteria, 17 patients (7.0%) had grade B, and five patients (2.0%) had grade C. The independent risk factor of incidence of pancreatic fistula is soft pancreatic parenchyma. However, soft pancreatic parenchyma did not predict underlying clinically relevant pancreatic fistula. The independent predictive factors of clinically relevant pancreatic fistula were serum albumin level ≤3.0 g/dl on postoperative day (POD) 4 and leukocyte counts >9,800 mm−3 on POD 4. Positive predictive value of the combination of two predictive factors for clinical relevant pancreatic fistula was 88%.

Conclusions

The combination of two factors on POD4, serum albumin level ≤3.0 g/dl and leukocyte counts >9,800 mm−3, is predictive of clinical relevant pancreatic fistula when diagnosed pancreatic fistula on POD 3 by ISGPF criteria.
The FAS gene, brain volume, and disease progression in Alzheimer's disease
Authors: Erten‐Lyons Deniz , Jacobson Anne , Kramer Patricia , Grupe Andrew , Kaye Jeffrey
Published: September 2009

Objective

We sought to identify single‐nucleotide polymorphisms (SNPs) associated with Alzheimer's disease (AD) progression and brain volume.

Methods

Ninety‐seven SNPs were genotyped in 243 subjects from a longitudinal study of healthy aging. Subjects who received a diagnosis of cognitive impairment (CI) at any study visit (before their most recent visit) and had DNA in the study's DNA bank were included. Progression of AD was defined as the duration from onset of CI to diagnosis of AD. Association of each of the 97 SNPs with AD progression was tested via Cox model. Those SNPs meeting a criterion of nominal significance (P < 0.05) for association with AD progression were reassessed to account for multiple testing by repeating the marker selection process in 10,000 random permutations. Next, the association between the one SNP that survived the multiple‐testing adjustment and brain volume was determined by multiple regression analysis in a subgroup of subjects for whom magnetic‐resonance imaging (MRI)‐derived brain‐volume data were available. Brain volumes were adjusted for age at MRI, gender, and time from MRI to onset of CI.

Results

The minor allele of rs1468063 in the FAS gene, which is member 6 of the tumor necrosis factor receptor superfamily, was significantly associated with faster AD progression after adjustment for multiple testing (Ppermutation = 0.049). The same allele in rs1468063 was associated with smaller brain volumes and larger ventricular volumes (P = 0.02 and 0.04, respectively).

Conclusions

The FAS gene, which plays a role in apoptosis, may be associated with AD by modulating the apoptosis and neuronal loss secondary to AD neuropathology.
Short-term effects of replacing milk with cola beverages on insulin-like growth factor-I and insulin–glucose metabolism: a 10 d interventional study in young men
Authors: Hoppe Camilla , Kristensen Mette , Boiesen Marlene , Kudsk Jane , Fleischer Michaelsen Kim , Mølgaard Christian
Published: September 2009

In the Western world, a trend towards increased consumption of carbonated soft drinks combined with a decreasing intake of milk is observed. This may affect circulating insulin-like growth factor I (IGF-I) and fasting insulin, as seen in pre-pubertal children. The present study was designed to reflect the trend of replacing milk with carbonated beverages in young men and to study the effects of this replacement on IGF-I, IGF-binding protein 3 (IGFBP-3), IGF-I:IGFBP-3 and glucose–insulin metabolism. A randomised, controlled crossover intervention study, in which eleven men aged 22–29 years were given a low-Ca diet in two 10 d periods with 10 d washout in between. In one period, they drank 2·5 litres of Coca Cola® per day and the other period 2·5 litres of semi-skimmed milk. Serum IGF-I, IGFBP-3 (RIA), insulin (fluoro immunoassay) and glucose (Cobas) were determined at baseline and end point of each intervention period. Insulin resistance and β-cell function were calculated with the homeostasis model assessment. A decrease in serum IGF-I was observed in the cola period compared with the milk period (P < 0·05). No effects of treatment were observed on IGFBP-3, IGF-I:IGFBP-3, insulin, glucose, insulin resistance or β-cell function. The present study demonstrates that high intake of cola over a 10 d period decreases total IGF-I compared with a high intake of milk, with no effect on glucose–insulin metabolism in adult men. It is unknown whether this is a transient phenomenon or whether it has long-term consequences.
The relationship between birth weight and insulin resistance in childhood
Authors: Lemos Jesuana O. , Rondó Patricia H. C. , Pereira Joilane A. , Oliveira Renata G. , Freire Maria B. S. , Sonsin Patricia B.
Published: September 2009

Chronic diseases that are typical of adulthood may originate in intra-uterine life through inadequate fetal development. The present epidemiological cohort study of 506 healthy children aged 5–8 years evaluated the relationship between birth weight and insulin resistance in an age group that has been assessed in few similar studies. Insulin concentration was determined by chemiluminescence and insulin resistance by the homeostasis model assessment (HOMA). Blood glucose, total cholesterol and fractions (LDL cholesterol and HDL cholesterol) and TAG concentrations were determined by automated enzymatic methods. Linear regression analysis investigated the relationship between birth weight (assessed as a continuous variable and in three categories: small for gestational age, SGA; adequate for gestational age and large for gestational age) and the HOMA index, using backward stepwise selection and biological models to explain the causal pathway of the relationship. There were negative associations between birth weight (P < 0·001), SGA (P = 0·027) and the HOMA index, and a positive association between waist circumference (P < 0·001) and the HOMA index. Considering the significant associations between birth weight and waist circumference (P < 0·001) and waist circumference and insulin resistance (P < 0·001), we can probably suspect that lower birth weight is a common cause of higher waist circumference and insulin resistance. In summary, the results of the present study showed increased insulin resistance in apparently healthy, young children, who had lower weight at birth and higher measurements of waist circumference. There is a need to develop public health policies that adopt preventive measures to promote adequate maternal-fetal and child development and enable early diagnosis of metabolic abnormalities.
Genetic relationships among napiergrass (Pennisetum purpureum Schum.) nursery accessions using AFLP markers
Authors: Harris Karen , Anderson William , Malik Ravindra
Published: September 2009

Pennisetum purpureum Schum. (napiergrass) is a perennial grass used for forage especially in South America and Africa. Over the last 30 years, a USDA–ARS nursery containing accessions collected from all over the world has been established in Tifton, Georgia. The study reported here was conducted to assess the molecular genetic variation and genetic relatedness among 89 accessions from the Tifton nursery using amplified fragment length polymorphism markers, morphological data and ploidy level. Using 218 polymorphic markers from eight selective primer combinations, the 89 accessions were clustered into five groups using a principal components analysis and a dendrogram based on Dice similarity estimates and unweighted pair group method with arithmetic average clustering. These five groups include three groups collected from Kenya, a group from Puerto Rico, and accessions derived from the cultivar Merkeron. This research provides the first molecular characterization of the Tifton nursery, displays the relationships between accessions, and provides potential heterotic groups for napiergrass and pearl millet (Pennisetum glaucum (L.) R. Br.) breeding improvement.
Scaling of seismicity induced by nonlinear fluid‐rock interaction
Authors: Shapiro S. A. , Dinske C.
Published: September 2009

Fluid injections into geothermal systems sometimes can produce significant seismic events with magnitudes of up to 4. However, in the case of hydraulic fracturing of hydrocarbon reservoirs, such events occur extremely seldom. In the last case, in contrast to the former one, the structure of rocks is being actively destroyed (e.g., opening of tensile fractures) and the fluid‐rock interaction is strongly nonlinear (e.g., a strong increase of permeability). What is the role of this nonlinearity? We consider nonlinear pore pressure diffusion to explain features of seismicity. We formulate seismicity triggering front. Its propagation is sensitive to a grade of nonlinearity, to spatial dimension of diffusion, and to the injection rate. We show that a probability of an event with a magnitude larger than a given one increases proportionally to the injected mass. An increase of this probability with time is insensitive to the nonlinearity. We compare different borehole experiments. In some cases the injection produces clearly nonlinear impact on rocks. In others this impact is approximately linear. We find a well agreement with our theory. We observe an insensitivity of temporal increments of magnitude probability to the grade of nonlinearity. These increments are controlled by injection‐rate increments. In contrast, nonlinear fluid‐rock interactions are characterized by a strong dominance of small earthquakes. Defects activated by a nonlinear diffusion possibly obey Gutenberg‐Richter statistics with anomalous high b values. In the case of a linear diffusion, magnitude distributions of events are probably inherited from pre‐existing fracture systems.
An approach to estimate global biomass burning emissions of organic and black carbon from MODIS fire radiative power
Authors: Vermote Eric , Ellicott Evan , Dubovik Oleg , Lapyonok Tatyana , Chin Mian , Giglio Louis , Roberts Gareth J.
Published: September 2009

Biomass burning is the main global source of fine primary carbonaceous aerosols in the form of organic carbon (OC) and black carbon (BC). We present an approach to estimate biomass burning aerosol emissions based on the measurement of radiative energy released during combustion. We make use of both Aqua and Terra MODIS observations to estimate the fire radiative energy using a simple model to parameterize the fire diurnal cycle based on the long‐term ratio between Terra and Aqua MODIS FRP. The parameterization is developed using cases of frequent (up to 12 times daily) MODIS observations, geostationary data from SEVIRI, and precessing observations from TRMM VIRS. FRE‐based emission coefficients for the organic and black carbon (OCBC) component of fine mode aerosols are computed from multiple regions encompassing grassland/savanna, tropical forest, and extratropical forest biomes using OCBC emission estimates derived from the MODIS fine mode aerosol product and an inverse aerosol transport model. The values of emission coefficients for OCBC retrieved were 2.7 ± 0.3 g/MJ for grassland/savanna, 8.6 ± 0.8 g/MJ for tropical forest, and 14.4 ± 0.8 g/MJ for extratropical forest. The FRE monthly data are then used to estimate OCBC emissions from biomass burning on a global basis. For 2001 to 2007, our annual estimates are comparable to previously published values. According to our estimate, the OCBC emissions are the largest for 2003 (18.8 Tg), roughly 20% above average and primarily driven by wildland fires in the Lake Baikal region (Russia).
Improved estimates of forest vegetation structure and biomass with a LiDAR‐optimized sampling design
Authors: Hawbaker Todd J. , Keuler Nicholas S. , Lesak Adrian A. , Gobakken Terje , Contrucci Kirk , Radeloff Volker C.
Published: September 2009

LiDAR data are increasingly available from both airborne and spaceborne missions to map elevation and vegetation structure. Additionally, global coverage may soon become available with NASA's planned DESDynI sensor. However, substantial challenges remain to using the growing body of LiDAR data. First, the large volumes of data generated by LiDAR sensors require efficient processing methods. Second, efficient sampling methods are needed to collect the field data used to relate LiDAR data with vegetation structure. In this paper, we used low‐density LiDAR data, summarized within pixels of a regular grid, to estimate forest structure and biomass across a 53,600 ha study area in northeastern Wisconsin. Additionally, we compared the predictive ability of models constructed from a random sample to a sample stratified using mean and standard deviation of LiDAR heights. Our models explained between 65 to 88% of the variability in DBH, basal area, tree height, and biomass. Prediction errors from models constructed using a random sample were up to 68% larger than those from the models built with a stratified sample. The stratified sample included a greater range of variability than the random sample. Thus, applying the random sample model to the entire population violated a tenet of regression analysis; namely, that models should not be used to extrapolate beyond the range of data from which they were constructed. Our results highlight that LiDAR data integrated with field data sampling designs can provide broad‐scale assessments of vegetation structure and biomass, i.e., information crucial for carbon and biodiversity science.
Silencing of the mitochondrial NADH shuttle component aspartate–glutamate carrier AGC1/Aralar1 in INS-1E cells and rat islets
Authors: Casimir Marina , Rubi Blanca , Frigerio Francesca , Chaffard Gaelle , Maechler Pierre
Published: September 2009

Transfer of reducing equivalents between cytosolic compartments and the mitochondrial matrix is mediated by NADH shuttles. Among these, the malate–aspartate shuttle has been proposed to play a major role in β-cells for the control of glucose-stimulated insulin secretion. AGC1 or Aralar1 (aspartate–glutamate carrier 1) is a key component of the malate–aspartate shuttle. Overexpression of AGC1 increases the capacity of the malate–aspartate shuttle, resulting in enhanced metabolism–secretion coupling, both in INS-1E cells and rat islets. In the present study, knockdown of AGC1 was achieved in the same β-cell models, using adenovirus-mediated delivery of shRNA (small-hairpin RNA). Compared with control INS-1E cells, down-regulation of AGC1 blunted NADH formation (−57%; P<0.05), increased lactate production (+16%; P<0.001) and inhibited glucose oxidation (−22%; P<0.01). This correlated with a reduced secretory response at 15 mM glucose (−25%; P<0.05), while insulin release was unchanged at intermediate 7.5 mM and basal 2.5 mM glucose. In isolated rat islets, efficient AGC1 knockdown did not alter insulin exocytosis evoked by 16.7 mM glucose. However, 4 mM amino-oxyacetate, commonly used to block transaminases of the malate–aspartate shuttle, inhibited glucose-stimulated insulin secretion to similar extents in INS-1E cells (−66%; P<0.01) and rat islets (−56%; P<0.01). These results show that down-regulation of the key component of the malate–aspartate shuttle AGC1 reduced glucose-induced oxidative metabolism and insulin secretion in INS-1E cells, whereas similar AGC1 knockdown in rat islets did not affect their secretory response.
IRAK1-independent pathways required for the interleukin-1-stimulated activation of the Tpl2 catalytic subunit and its dissociation from ABIN2
Authors: Handoyo Hosea , Stafford Margaret J. , McManus Eamon , Baltzis Dionissios , Peggie Mark , Cohen Philip
Published: September 2009

The protein kinase Tpl2 (tumour progression locus 2) is activated by LPS (lipopolysaccharide), TNFα (tumour necrosis factor α) and IL (interleukin)-1. Activation of the native Tpl2 complex by these agonists requires the IKKβ {IκB [inhibitor of NF-κB (nuclear factor κB)] kinase β}-catalysed phosphorylation of the p105/NF-κB1 subunit and is accompanied by the release of the catalytic subunit from both p105/NF-κB1 and another subunit ABIN2 (A20-binding inhibitor of NF-κB 2). In the present study we report that IL-1 activates the transfected Tpl2 catalytic subunit in an HEK (human embryonic kidney)-293 cell line that stably expresses the IL-1R (IL-1 receptor), but does not express the protein kinase IRAK1 (IL-1R-associated kinase). In these cells IL-1 does not activate IKKβ or induce the phosphorylation of p105/NF-κB1, and nor does the IKKβ inhibitor PS1145 prevent the IL-1-induced activation of transfected Tpl2. However, the IL-1-stimulated activation of transfected Tpl2 in IRAK1-null cells or activation of the endogenous Tpl2 complex in IRAK1-expressing cells is suppressed by the protein kinase inhibitor PP2 by a mechanism that does not involve inhibition of Src family protein tyrosine kinases. The IL-1-stimulated activation of transfected Tpl2 is accompanied by its phosphorylation at Thr290 and Ser400 and by enhanced phosphorylation of Ser62, which we demonstrate are autophosphorylation events catalysed by Tpl2 itself. We further show that IL-1 triggers the dissociation of Tpl2 from co-transfected ABIN2 in IRAK1-null IL-1R cells, which is not suppressed by PP2 or by the inhibition of Tpl2 or IKKβ. These studies identify two new signalling events involved in activation of the native Tpl2 complex by IL-1. First, the IRAK1-, IKKβ- and PP2-independent dissociation of Tpl2 from ABIN2; secondly, the IRAK1- and IKKβ-independent, but PP2-sensitive, activation of the Tpl2 catalytic subunit.
Lipid rafts as functional heterogeneity in cell membranes
Authors: Lingwood Daniel , Kaiser Hermann-Josef , Levental Ilya , Simons Kai
Published: September 2009

Biological membranes are not structurally passive solvents of amphipathic proteins and lipids. Rather, it appears their constituents have evolved intrinsic characteristics that make homogeneous distribution of components unlikely. As a case in point, the concept of lipid rafts has received considerable attention from biologists and biophysicists since the formalization of the hypothesis more than 10 years ago. Today, it is clear that sphingolipid and cholesterol can self-associate into micron-scaled phases in model membranes and that these lipids are involved in the formation of highly dynamic nanoscale heterogeneity in the plasma membrane of living cells. However, it remains unclear whether these entities are manifestations of the same principle. A powerful means by which the molecular organization of rafts can be assessed is through analysis of their functionalized condition. Raft heterogeneity can be activated to coalesce and laterally reorganize/stabilize bioactivity in cell membranes. Evaluation of this property suggests that functional raft heterogeneity arises through principles of lipid-driven phase segregation coupled to additional chemical specificities, probably involving proteins.
Dividing the goods: co-ordination of chromosome biorientation and mitotic checkpoint signalling by mitotic kinases
Authors: Kops Geert J.P.L.
Published: September 2009

Error-free chromosome segregation during cell division relies on chromosome biorientation and mitotic checkpoint activity. A group of unrelated kinases controls various aspects of both processes. The present short review outlines our current understanding of the roles of these kinases in maintaining chromosomal stability.
The assembly of lipid droplets and its relation to cellular insulin sensitivity
Authors: Boström Pontus , Andersson Linda , Li Lu , Perkins Rosie , Højlund Kurt , Borén Jan , Olofsson Sven-Olof
Published: September 2009

The assembly of lipid droplets is dependent on PtdIns(4,5)P2 that activates PLD1 (phospholipase D1), which is important for the assembly process. ERK2 (extracellular-signal-regulated kinase 2) phosphorylates the motor protein dynein and sorts it to lipid droplets, allowing them to be transported on microtubules. Lipid droplets grow in size by fusion, which is dependent on dynein and the transfer on microtubules, and is catalysed by the SNARE (soluble N-ethylmaleimide-sensitive fusion protein-attachment protein receptor) proteins SNAP-23 (23 kDa synaptosome-associated protein), syntaxin-5 and VAMP-4 (vesicle-associated protein 4). SNAP-23 is also involved in the insulin-dependent translocation of the glucose transporter GLUT4 to the plasma membrane. Fatty acids induce a missorting of SNAP-23, from the plasma membrane to the interior of the cell, resulting in cellular insulin resistance that can be overcome by increasing the levels of SNAP-23. The same missorting of SNAP-23 occurs in vivo in skeletal-muscle biopsies from patients with T2D (Type 2 diabetes). Moreover, there was a linear relation between the amount of SNAP-23 in the plasma membrane from human skeletal-muscles biopsies and the systemic insulin-sensitivity. Syntaxin-5 is low in T2D patients, which leads to a decrease in the insulin-dependent phosphorylation of Akt (also known as protein kinase B). Thus both SNAP-23 and syntaxin-5 are highly involved in the development of insulin resistance.
Hepatitis C virus: viral proteins on the move
Authors: McLauchlan John
Published: September 2009

There is now increasing evidence that LDs (lipid droplets) play a central role in the production of infectious HCV (hepatitis C virus) and participate in virus assembly. Two viral proteins, namely core, which forms the capsid, and NS5A (non-structural 5A protein), a component of complexes engaged in viral RNA synthesis, are detected at LD surfaces in infected cells. Interactions between the two proteins may be critical for anchoring RNA replication sites to droplets for initiating virus assembly. The requirements for targeting of core in particular has received considerable attention since the nature of its interaction with LDs could play a key role in determining the efficiency of virion production. As well as attaching to droplets, core is able to alter their intracellular distribution and direct them towards the microtubule organizing centre. Inhibitors that disrupt microtubules block this redistribution by core and there is a concomitant decrease in virus production. Therefore altered dynamics of LDs may contribute to HCV assembly and release. The purpose of targeting LDs by HCV may be linked to their contribution to the formation of VLDLs (very-low-density lipoproteins) in hepatocytes since virus circulating in infected patients is associated with lipoprotein. Thus HCV may utilize the role played by LDs in the formation of lipoprotein particles as part of its life cycle and access this pathway by direct interaction of viral components with these intracellular storage organelles.
Microsignalosomes: spatially resolved receptor signalling
Authors: Treanor Bebhinn , Harwood Naomi E. , Batista Facundo D.
Published: September 2009

B-cells are a critical component of the adaptive immune system. As such, B-cells survey the body and mount appropriate protective responses to pathogen-derived antigens, resulting in the production of specific antibodies and induction of immunological memory. Given the effectiveness of these responses in selectively eliminating pathogenic infections, it is clear that the processes underlying antigen-induced B-cell activation must be highly regulated. Somewhat surprisingly given the specialized function of these immune cells, the BCR (B-cell receptor) functions similarly to receptors of the tyrosine kinase family that are commonplace in biology, as BCR ligation with antigen leads to B-cell proliferation and differentiation. In the Lymphocyte Interaction Laboratory, we are particularly interested in characterizing the very early molecular events underlying B-cell activation using a combination of cutting-edge high-resolution and in vivo imaging techniques.
The delivery of endocytosed cargo to lysosomes
Authors: Luzio J. Paul , Parkinson Michael D.J. , Gray Sally R. , Bright Nicholas A.
Published: September 2009

In mammalian cells, endocytosed cargo that is internalized through clathrin-coated pits/vesicles passes through early endosomes and then to late endosomes, before delivery to lysosomes for degradation by proteases. Late endosomes are MVBs (multivesicular bodies) with ubiquitinated membrane proteins destined for lysosomal degradation being sorted into their luminal vesicles by the ESCRT (endosomal sorting complex required for transport) machinery. Cargo is delivered from late endosomes to lysosomes by kissing and direct fusion. These processes have been studied in live cell experiments and a cell-free system. Late endosome–lysosome fusion is preceded by tethering that probably requires mammalian orthologues of the yeast HOPS (homotypic fusion and vacuole protein sorting) complex. Heterotypic late endosome–lysosome membrane fusion is mediated by a trans-SNARE (soluble N-ethylmaleimide-sensitive factor-attachment protein receptor) complex comprising Syntaxin7, Vti1b, Syntaxin8 and VAMP7 (vesicle-associated membrane protein 7). This differs from the trans-SNARE complex required for homotypic late endosome fusion in which VAMP8 replaces VAMP7. VAMP7 is also required for lysosome fusion with the plasma membrane and its retrieval from the plasma membrane to lysosomes is mediated by its folded N-terminal longin domain. Co-ordinated interaction of the ESCRT, HOPS and SNARE complexes is required for cargo delivery to lysosomes.
Dissecting dynamin's role in clathrin-mediated endocytosis
Authors: Mettlen Marcel , Pucadyil Thomas , Ramachandran Rajesh , Schmid Sandra L.
Published: September 2009

The GTPase dynamin is essential for CME (clathrin-mediated endocytosis), but its exact function and mechanism of action have been controversial. Here, we review findings that have led to the current models for dynamin function, either as a mechanochemical enzyme driving membrane fission or as a regulatory GTPase monitoring rate-limiting steps in CME. However, these models are not mutually exclusive and subsequent studies have provided evidence for both dynamin functions. Recent evidence derived from divergent in vivo and in vitro approaches suggests that dynamin plays a dual role in CME, functioning at early stages as a fidelity monitor to regulate clathrin-coated pit maturation and at later stages to directly catalyse membrane fission and clathrin-coated vesicle formation.
Rab7 and the CMT2B disease
Authors: Cogli Laura , Piro Francesco , Bucci Cecilia
Published: September 2009

The CMT2B (Charcot–Marie–Tooth type 2B) disease is an autosomal dominant axonal neuropathy. Sensory loss, distal muscle weakness and wasting, frequent foot ulcers and amputations of the toes due to frequent infections characterize this neuropathy. Four missense mutations in the rab7 gene have been identified as causative of the disease. Rab7 is a small G-protein of the Rab family that controls vesicular transport to late endosomes and lysosomes in the endocytic pathway. The CMT2B-associated mutant Rab7 proteins show altered nucleotide dissociation rates and impaired GTPase activity. In addition, these mutant proteins are predominantly in the GTP-bound form when expressed in human cells and they are able to rescue Rab7 function in Rab7-depleted cells. Thus these mutations generate activated forms of Rab7 that are responsible for the development of the disease. In spite of these results, there are still important gaps in our understanding of the mechanism underlying CMT2B. Indeed, how these mutations in the rab7 gene affect specifically peripheral neurons leading to an axonal pathology in CMT2B is not clear, and it is a particularly puzzling and challenging issue in view of the fact that Rab7 is a ubiquitous protein. The present review discusses possible molecular mechanisms underlying CMT2B.
Walking, hopping, diffusing and braking modes of kinesin-5
Authors: Kaseda Kuniyoshi , McAinsh Andrew D. , Cross Robert A.
Published: September 2009

It is clear that the main cellular mission of the molecular motor kinesin-5 (known as Eg5 in vertebrates) is to cross-link antiparallel microtubules and to slide them apart, thus playing a critical role during bipolar spindle formation. Nonetheless, important questions about the cell biological and biophysical mechanisms of Eg5 remain unanswered. With the 20th ‘birthday’ of Eg5 approaching, we discuss recent insights into the in vitro and in vivo functions of Eg5, in the context of our own recent work.
Bicaudal-D and its role in cargo sorting by microtubule-based motors
Authors: Dienstbier Martin , Li Xuan
Published: September 2009

Many cytoplasmic cargoes are transported along microtubules using dynein or kinesin molecular motors. As the sorting machinery of the cell needs to be tightly controlled, associated factors are employed to either recruit cargoes to motors or to regulate their activities. In the present review, we concentrate on the BicD (Bicaudal-D) protein, which has recently emerged as an essential element for transport of several important cargoes by the minus-end-directed motor cytoplasmic dynein. BicD was proposed to be a linker bridging cargo and dynein, although recent studies suggest that it may also have roles in the regulation of cargo motility. Here we summarize the current knowledge of the role that BicD plays in the transport of diverse cellular constituents. We catalogue the molecular interactions that underpin these functions and also highlight important questions to be addressed in the future.
The role of vesicle trafficking in epithelial cell motility
Authors: Fletcher Sarah J. , Rappoport Joshua Z.
Published: September 2009

Cell motility is important for many physiological and pathological processes including organ development, wound healing, cancer metastasis and correct immune responses. In particular, epithelial wound healing is both a medically relevant topic and a common experimental model. Mechanisms underlying generation of a polarized cell and maintenance of a motile phenotype during steady-state migration are not well understood. Polarized trafficking of bulk membrane and cell adhesion molecules has been implicated in regulation of cell motility. The present review focuses on the role of different trafficking pathways in epithelial cell migration, including clathrin-mediated endocytosis, caveolar endocytosis, exocytosis of biosynthetic cargo, ‘short-loop’ and ‘long-loop’ endosomal recycling.
Is the brain arachidonic acid cascade a common target of drugs used to manage bipolar disorder?
Authors: Bazinet Richard P.
Published: September 2009

Although lithium has been used therapeutically to treat patients with bipolar disorder for over 50 years, its mechanism of action, as well as that of other drugs used to treat bipolar disorder, is not agreed upon. In the present paper, I review studies in unanaesthetized rats using a neuropharmacological approach, combined with kinetic, biochemical and molecular biology techniques, demonstrating that chronic administration of three commonly used mood stabilizers (lithium, valproic acid and carbamazepine), at therapeutically relevant doses, selectively target the brain arachidonic acid cascade. Upon chronic administration, lithium and carbamazepine decrease the binding activity of activator protein-2 and, in turn, the transcription, translation and activity of its arachidonic acid-selective calcium-dependent phospholipase A2 gene product, whereas chronic valproic acid non-competitively inhibits long-chain acyl-CoA synthetase. The net overlapping effects of the three mood stabilizers are decreased turnover of arachidonic acid, but not of docosahexaenoic acid, in rat brain phospholipids, as well as decreased brain cyclo-oxygenase-2 and prostaglandin E2. As an extension of this theory, drugs that are thought to induce switching to mania, especially when administered during bipolar depression (fluoxetine and imipramine), up-regulate enzymes of the arachidonic acid cascade and turnover of arachidonic acid in rat brain phospholipids. Future basic and clinical studies on the arachidonic acid hypothesis of bipolar disorder are warranted.