bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of plant dynamic processes on African vegetation responses to climate change: Analysis using the spatially explicit individual‐based dynamic global vegetation model (SEIB‐DGVM)
Authors: Sato Hisashi , Ise Takeshi
Published: June 2012

We applied a dynamic global vegetation model (DGVM) to the African continent. After calibration, the model reproduced geographical distributions of the continent's biomes, annual gross primary productivity (GPP), and biomass under current climatic conditions. The model is driven by the Intergovernmental Panel on Climate Change (IPCC) Special Report on Emission Scenarios (SRES) A1B scenario of rising CO2, and by climate changes during the twenty‐first century resulting from the change in CO2concentrations, simulated by a coupled Model for Interdisciplinary Research on Climate (MIROC) ocean atmosphere model. Simulations under this condition revealed time lags between environmental change and biome change, with the extent of these lags depending largely on the type of biome change. A switch in forest type was accompanied by the longest delay in biome change among all changes classified, indicating that resident trees largely prevent the establishment of nonresident tree types adapted to the new environment, and that tree growth requires additional years after successful establishment. In addition, assumptions for tree dispersal, which determine whether nonresident tree types can be established, modified the patterns of biome change under the twenty‐first‐century environment: under the assumption that nonresident tree types cannot be established even if environmental conditions change, the extent of the forest type switch and the development of forest and savanna were suppressed, while forest dieback was enhanced. These changes accompanied a slowing of the increasing trend in net primary productivity (NPP), biomass, and soil carbon during the twenty‐first century and in subsequent years. These results quantitatively demonstrate that both patch dynamics and invasive tree recruitment significantly modify the transient change in vegetation distribution and function under a changing environment on the African continent.
Loss of fused in sarcoma (FUS) promotes pathological Tau splicing
Authors: Orozco Denise , Tahirovic Sabina , Rentzsch Kristin , Schwenk Benjamin M , Haass Christian , Edbauer Dieter
Published: June 2012

A subset of amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD) patients present pathological redistribution and aggregation of the nuclear protein fused in sarcoma (FUS) in the cytoplasm. Although FUS associates with the spliceosomal complex, no endogenous neuronal splicing targets have been identified. Here we identify Tau mRNA as a physiological splicing target of FUS. In mouse brain, FUS directly binds to Tau pre‐mRNA, and knockdown of FUS in hippocampal neurons leads to preferential inclusion of Tau exons 3 and 10. FUS knockdown causes significant growth cone enlargement and disorganization reminiscent of Tau loss of function. These findings suggest that disturbed cytoskeletal function and enhanced expression of the neurodegeneration‐associated Tau exon 10 might contribute to FTLD/ALS with FUS inclusions.
Protein arginine methyltransferase 5 is essential for growth of lung cancer cells
Authors: Gu Zhongping , Gao Shen , Zhang Fahao , Wang Zhiqiang , Ma Wencai , Davis Richard E. , Wang Zhengxin
Published: June 2012

PRMT5 (protein arginine methyltransferase 5) is an enzyme that catalyses transfer of methyl groups from S-adenosyl methionine to the arginine residues of histones or non-histone proteins and is involved in a variety of cellular processes. Although it is highly expressed in some tumours, its direct role in cancer growth has not been fully investigated. In the present study, in human lung tissue samples we found that PRMT5 was highly expressed in lung cancer cells, whereas its expression was not detectable in benign lung tissues. Silencing PRMT5 expression strongly inhibited proliferation of lung adenocarcinoma A549 cells in tissue culture, and silencing PRMT5 expression in A549 cells also abolished growth of lung A549 xenografts in mice. In vitro and in vivo studies showed that the cell growth arrest induced by loss of PRMT5 expression was partially attributable to down-regulation of fibroblast growth factor receptor signalling. These results suggest that PRMT5 and its methyltransferase activity is essential for proliferation of lung cancer cells and may serve as a novel target for the treatment of lung cancer.
A model for the human tear film with heating from within the eye
Authors: Li Longfei , Braun R. J.
Published: June 2012

A model for tear film dynamics and cooling during the interblink period is formulated that includes heat transfer from the interior of the eye. Lubrication theory is used to derive an equation for the thickness of the film; the nonlinear partial differential equation for the thickness is solved subject to either a fixed temperature at the substrate or with heat diffusion from within two different model rectangular domains. The model domains are simplified geometries that represent the anterior eye and that may include the cornea and some aqueous humor; one model domain is asymptotically thin (thin substrate) and the other has finite thickness (thick substrate). The thick substrate case captures temperature decreases that are observed in vivo, while the thin substrate and fixed temperature models do not. Parameters to reproduce observed temperature decreases are found.
Destruction of hydrogen bonds of poly(N-isopropylacrylamide) aqueous solution by trimethylamine N-oxide
Authors: Reddy P. Madhusudhana , Taha Mohamed , Venkatesu Pannuru , Kumar Awanish , Lee Ming-Jer
Published: June 2012

Trimethylamine N-oxide (TMAO) is a compatible or protective osmolyte that stabilizes the protein native structure through non-bonding mechanism between TMAO and hydration surface of protein. However, we have shown here first time the direct binding mechanism for naturally occurring osmolyte TMAO with hydration structure of poly(N-isopropylacrylamide) (PNIPAM), an isomer of polyleucine, and subsequent aggregation of PNIPAM. The influence of TMAO on lower critical solution temperature (LCST) of PNIPAM was investigated as a function of TMAO concentration at different temperatures by fluorescence spectroscopy, viscosity (η), multi angle dynamic light scattering, zeta potential, and Fourier transform infrared (FTIR) spectroscopy measurements. To address some of the basis for further analysis of FTIR spectra of PNIPAM, we have also measured FTIR spectra for the monomer of N-isopropylacrylamide (NIPAM) in deuterium oxide (D2O) as a function of TMAO concentration. Our experimental results purportedly elucidate that the LCST values decrease with increasing TMAO concentration, which is mainly contributing to the direct hydrogen bonding of TMAO with the water molecules that are bound to the amide (–CONH) functional groups of the PNIPAM. We believed that the present work may act as a ladder to reach the heights of understanding of molecular mechanism between TMAO and macromolecule.
Potential formulation of the dispersion relation for a uniform, magnetized plasma with stationary ions in terms of a vector phasor
Authors: Johnson Robert W.
Published: June 2012

The derivation of the helicon dispersion relation for a uniform plasma with stationary ions subject to a constant background magnetic field is reexamined in terms of the potential formulation of electrodynamics. Under the same conditions considered by the standard derivation, the nonlinear self-coupling between the perturbed electron flow and the potential it generates is addressed. The plane wave solution for general propagation vector is determined for all frequencies and expressed in terms of a vector phasor. The behavior of the solution as described in vacuum units depends upon the ratio of conductivity to the magnitude of the background field. Only at low conductivity and below, the cyclotron frequency can significant propagation occur as determined by the ratio of skin depth to wavelength.
Optical analysis of doped ZnO thin films using nonparabolic conduction-band parameters
Authors: Kim J. S. , Jeong J.-h. , Park J. K. , Baik Y. J. , Kim I. H. , Seong T.-Y. , Kim W. M.
Published: June 2012

The optical properties of impurity doped ZnO thin films were analyzed by taking into account the nonparabolicity in the conduction-band and the optically determined carrier concentration and mobility were correlated with those measured by Hall measurement. The Drude parameters obtained by applying a simple Drude model combined with the Lorentz oscillator model for the optical transmittance and reflectance spectrum were analyzed by using the carrier density dependent bare band effective mass determined by the first-order nonparabolicity approximation. The squared plasma energy multiplied by the carrier density dependent effective mass yielded fairly linear relationship with respect to the carrier concentration in wide carrier density range of 1019 − 1021 cm−3, verifying the applicability of the nonparabolicity parameter for various types of impurity doped ZnO thin films. The correlation between the optical and Hall analyses was examined by taking the ratios of optical to Hall measurements for carrier density, mobility, and resistivity by introducing a parameter, Rdl, which represents the ratio of the resistances to electron transport from the inside of the lattice and from the crystallographic defects. For both the carrier concentration and mobility, the ratios of optical to Hall measurements were shown to exhibit a monotonically decreasing function of Rdl, indicating that the parameter Rdl could be used as a yardstick in correlating the optically determined carrier density and mobility with those measured by Hall analysis.
Formation and evolution of oxygen-vacancy clusters in lead and tin doped silicon
Authors: Londos C. A. , Aliprantis D. , Sgourou E. N. , Chroneos A. , Pochet P.
Published: June 2012

Infrared spectroscopy (IR) measurements were used to investigate the effect of lead (Pb), tin (Sn), and (Pb, Sn) codoping on electron radiation-induced defects in silicon (Si). The study was mainly focused on oxygen-vacancy (VOn) clusters and in particular their formation and evolution upon annealing. It was determined that Pb causes a larger reduction in the production of the VO defect than Sn. In (Pb, Sn) co-doped Si isochronal anneals revealed that the evolution of VO increases substantially at ∼170 °C. This is attributed to the release of V from the SnV pair. Interestingly, in the corresponding evolution curves of VO in the Sn- and the Pb-doped samples, this inverse annealing stage is also present for the former while it is not present for the latter. This is attributed to the formation of PbV pairs that do not dissociate below 280 °C. The partial capture of V by Sn in co-doped samples is rationalized through the higher compressive local strain around Pb atoms that leads to a retardation of vacancy diffusion. The conversion of VO to the VO2 defect is substantially reduced in the Pb-doped sample. The evolution curves of VO and VO2 clusters in the isovalent doped Si samples hint the production of VO2 from other mechanisms (i.e., besides VO + Oi → VO2). For larger VOn clusters (n = 3,4), the signals are very weak in the Pb-doped sample, whereas for n ≥ 5, they are not present in the spectra. Conversely, bands related with the VO5 and VOnCs defects are present in the spectra of the Sn-doped and (Pb, Sn) codoped Si.
Charged-particle spectroscopy for diagnosing shock ρR and strength in NIF implosions
Authors: Zylstra A. B. , Frenje J. A. , Séguin F. H. , Rosenberg M. J. , Rinderknecht H. G. , Johnson M. Gatu , Casey D. T. , Sinenian N. , Manuel M. J.-E. , Waugh C. J. , Sio H. W. , Li C. K. , Petrasso R. D. , Friedrich S. , Knittel K. , Bionta R. , McKernan M. , Callahan D. , Collins G. W. , Dewald E. , Döppner T. , Edwards M. J. , Glenzer S. , Hicks D. G. , Landen O. L. , London R. , Mackinnon A. , Meezan N. , Prasad R. R. , Ralph J. , Richardson M. , Rygg J. R. , Sepke S. , Weber S. , Zacharias R. , Moses E. , Kilkenny J. , Nikroo A. , Sangster T. C. , Glebov V. , Stoeckl C. , Olson R. , Leeper R. J. , Kline J. , Kyrala G. , Wilson D.
Published: June 2012

The compact Wedge Range Filter (WRF) proton spectrometer was developed for OMEGA and transferred to the National Ignition Facility (NIF) as a National Ignition Campaign diagnostic. The WRF measures the spectrum of protons from D-3He reactions in tuning-campaign implosions containing D and 3He gas; in this work we report on the first proton spectroscopy measurement on the NIF using WRFs. The energy downshift of the 14.7-MeV proton is directly related to the total ρR through the plasma stopping power. Additionally, the shock proton yield is measured, which is a metric of the final merged shock strength.
Strong terahertz radiation from relativistic laser interaction with solid density plasmas
Authors: Li Y. T. , Li C. , Zhou M. L. , Wang W. M. , Du F. , Ding W. J. , Lin X. X. , Liu F. , Sheng Z. M. , Peng X. Y. , Chen L. M. , Ma J. L. , Lu X. , Wang Z. H. , Wei Z. Y. , Zhang J.
Published: June 2012

We report a plasma-based strong THz source generated in intense laser-solid interactions at relativistic intensities >1018 W/cm2. Energies up to 50 μJ/sr per THz pulse is observed when the laser pulses are incident onto a copper foil at 67.5°. The temporal properties of the THz radiation are measured by a single shot, electro-optic sampling method with a chirped laser pulse. The THz radiation is attributed to the self-organized transient fast electron currents formed along the target surface. Such a source allows potential applications in THz nonlinear physics and provides a diagnostic of transient currents generated in intense laser-solid interactions.
Evaluation of the evolution of jaw morphology in New World hirudiniform leeches, with a description of a new blood-feeding species of Oxyptychus (Annelida:Hirudiniformes) from the Peruvian Amazon
Authors: Oceguera-Figueroa Alejandro , Barrio Amalie K. , Aldea-Guevara Maria I. , Siddall Mark E.
Published: June 2012

Morphological characters of well-established taxonomic utility are infrequently examined for their relative phylogenetic consistency. Second only to characters of reproductive anatomy, jaw morphology and dentition commonly are employed as diagnostic characters for hirudiniform leeches, yet these features are highly variable across the group. Patterns of change were investigated for number of jaws and number of denticles per jaw in a phylogenetic context across 17 hirudiniform leeches representing three families. Phylogeny reconstruction employed 16 morphological characters, as well as two nuclear and two mitochondrial loci, and was evaluated with parsimony and likelihood. Rather than constrain the ancestral number of denticles to extant states, this meristic was optimised with squared-change parsimony. The degree to which dentition patterns were explained by phylogenetic relationships was assessed against a null distribution defined by permutation of extant states across terminals. Dentition was found to be non-randomly explained by phylogeny and, thus, corroborative of relationships among hirudiniform leeches as well as of the uniqueness of a new species of Oxyptychus described here from the Peruvian Amazon.
Systematic revision and phylogeny of the Australian myrmecomorphic seed bug genus Daerlac Signoret (Insecta:Heteroptera:Rhyparochromidae:Udeocorini)
Authors: Cassis Gerasimos , Symonds Celia
Published: June 2012

The Australian endemic ant-mimetic seed bug genus Daerlac is revised. This paper provides a redescription of the genus Daerlac and four species: D. apicalis, D. cephalotes, D. nigricans and D. picturatus. Daerlac tricolor is synonomised with D. cephalotes. A taxonomic key to species is provided. Known distributions of D. apicalis, D. nigricans and D. picturatus are each extended beyond previously known ranges. Daerlac species are found predominantly in temperate open forest and woodlands in association with ants and eucalypts. All species are broadly distributed and there is a high degree of overlap in distributions. They are seed predators found on the ground, in leaf litter, under bark or on trunks of eucalypts, and putatively forage on post-dispersed seeds. Cladistic analysis of morphological characters finds that the four species of Daerlac form two well-supported sister-groups (D. apicalis + D. picturatus, and D. cephalotes + D. nigricans). A discussion of the distribution, biology and myrmecomorphy of the genus is provided, and the tribal placement of Daerlac and its relationship to Laryngodus are discussed.
Functional diversity within the simple gut microbiota of the honey bee
Authors: Engel Philipp , Martinson Vincent G. , Moran Nancy A.
Published: June 2012

Animals living in social communities typically harbor a characteristic gut microbiota important for nutrition and pathogen defense. Accordingly, in the gut of the honey bee,
Apis mellifera
, a distinctive microbial community, composed of a taxonomically restricted set of species specific to social bees, has been identified. Despite the ecological and economical importance of honey bees and the increasing concern about population declines, the role of their gut symbionts for colony health and nutrition is unknown. Here, we sequenced the metagenome of the gut microbiota of honey bees. Unexpectedly, we found a remarkable degree of genetic diversity within the few bacterial species colonizing the bee gut. Comparative analysis of gene contents suggests that different species harbor distinct functional capabilities linked to host interaction, biofilm formation, and carbohydrate breakdown. Whereas the former two functions could be critical for pathogen defense and immunity, the latter one might assist nutrient utilization. In a γ-proteobacterial species, we identified genes encoding pectin-degrading enzymes likely involved in the breakdown of pollen walls. Experimental investigation showed that this activity is restricted to a subset of strains of this species providing evidence for niche specialization. Long-standing association of these gut symbionts with their hosts, favored by the eusocial lifestyle of honey bees, might have promoted the genetic and functional diversification of these bee-specific bacteria. Besides revealing insights into mutualistic functions governed by the microbiota of this important pollinator, our findings indicate that the honey bee can serve as a model for understanding more complex gut-associated microbial communities.
Evolution of music by public choice
Authors: MacCallum Robert M. , Mauch Matthias , Burt Austin , Leroi Armand M.
Published: June 2012

Music evolves as composers, performers, and consumers favor some musical variants over others. To investigate the role of consumer selection, we constructed a Darwinian music engine consisting of a population of short audio loops that sexually reproduce and mutate. This population evolved for 2,513 generations under the selective influence of 6,931 consumers who rated the loops’ aesthetic qualities. We found that the loops quickly evolved into music attributable, in part, to the evolution of aesthetically pleasing chords and rhythms. Later, however, evolution slowed. Applying the Price equation, a general description of evolutionary processes, we found that this stasis was mostly attributable to a decrease in the fidelity of transmission. Our experiment shows how cultural dynamics can be explained in terms of competing evolutionary forces.
The effects of relaxing music for anxiety control on competitive sport anxiety
Authors: Elliott Dave , Polman Remco , Taylor Julie
Published: June 2012

This investigation examined the effects of relaxing music for anxiety control on measures of competitive state anxiety and the performance of a simple motor skill. Seventy‐two undergraduate students volunteered to participate in the study. Participants were informed that they would be required to partake in a sport competition, possibly with an audience present, and possibly whilst being filmed. Participants were randomly allocated to one of three intervention conditions, listening to relaxing music for anxiety control, listening to non‐relaxing music or a no music control. During the 10‐minute intervention period, measures of anxiety (CSAI‐2R, subjective relaxation and HR) were taken on three occasions (baseline, pre‐intervention and post‐intervention). Repeated measures MANOVA showed that all three interventions provoked significant reductions in competitive state anxiety. Condition had no impact upon any of the DVs. These results suggest that listening to relaxing music for anxiety control was no more effective at reducing competitive state anxiety than non‐relaxing music or a period of silence. ES, mean difference and 90% CI data did however provide some support for the application of relaxing music for anxiety control. There were no between‐condition differences in motor task performance.
A Second Look at the Logic of Explanatory Power (with Two Novel Representation Theorems)
Authors: Crupi Vincenzo , Tentori Katya
Published: June 2012

We discuss the probabilistic analysis of explanatory power and prove a representation theorem for posterior ratio measures recently advocated by Schupbach and Sprenger. We then prove a representation theorem for an alternative class of measures that rely on the notion of relative probability distance. We end up endorsing the latter, as relative distance measures share the properties of posterior ratio measures that are genuinely appealing, while overcoming a feature that we consider undesirable. They also yield a telling result concerning formal accounts of explanatory power versus inductive confirmation, thereby bridging our discussion to a so-called no-miracle argument.
Associating microbiome composition with environmental covariates using generalized UniFrac distances
Authors: Chen Jun , Bittinger Kyle , Charlson Emily S. , Hoffmann Christian , Lewis James , Wu Gary D. , Collman Ronald G. , Bushman Frederic D. , Li Hongzhe
Published: June 2012

Motivation: The human microbiome plays an important role in human disease and health. Identification of factors that affect the microbiome composition can provide insights into disease mechanism as well as suggest ways to modulate the microbiome composition for therapeutical purposes. Distance-based statistical tests have been applied to test the association of microbiome composition with environmental or biological covariates. The unweighted and weighted UniFrac distances are the most widely used distance measures. However, these two measures assign too much weight either to rare lineages or to most abundant lineages, which can lead to loss of power when the important composition change occurs in moderately abundant lineages.

Results: We develop generalized UniFrac distances that extend the weighted and unweighted UniFrac distances for detecting a much wider range of biologically relevant changes. We evaluate the use of generalized UniFrac distances in associating microbiome composition with environmental covariates using extensive Monte Carlo simulations. Our results show that tests using the unweighted and weighted UniFrac distances are less powerful in detecting abundance change in moderately abundant lineages. In contrast, the generalized UniFrac distance is most powerful in detecting such changes, yet it retains nearly all its power for detecting rare and highly abundant lineages. The generalized UniFrac distance also has an overall better power than the joint use of unweighted/weighted UniFrac distances. Application to two real microbiome datasets has demonstrated gains in power in testing the associations between human microbiome and diet intakes and habitual smoking.

Availability:  http://cran.r-project.org/web/packages/GUniFrac

Contact:  hongzhe@upenn.edu

Supplementary information:  Supplementary data are available at Bioinformatics online.
Bluues server: electrostatic properties of wild-type and mutated protein structures
Authors: Walsh Ian , Minervini Giovanni , Corazza Alessandra , Esposito Gennaro , Tosatto Silvio C. E. , Fogolari Federico
Published: June 2012

Motivation: Electrostatic calculations are an important tool for deciphering many functional mechanisms in proteins. Generalized Born (GB) models offer a fast and convenient computational approximation over other implicit solvent-based electrostatic models. Here we present a novel GB-based web server, using the program Bluues, to calculate numerous electrostatic features including pKa-values and surface potentials. The output is organized allowing both experts and beginners to rapidly sift the data. A novel feature of the Bluues server is that it explicitly allows to find electrostatic differences between wild-type and mutant structures.

Availability: The Bluues server, examples and extensive help files are available for non-commercial use at URL: http://protein.bio.unipd.it/bluues/.

Contact:  silvio.tosatto@unipd.it
Gene structure in the sea urchin Strongylocentrotus purpuratus based on transcriptome analysis
Authors: Tu Qiang , Cameron R. Andrew , Worley Kim C. , Gibbs Richard A. , Davidson Eric H.
Published: June 2012

A comprehensive transcriptome analysis has been performed on protein-coding RNAs of Strongylocentrotus purpuratus, including 10 different embryonic stages, six feeding larval and metamorphosed juvenile stages, and six adult tissues. In this study, we pooled the transcriptomes from all of these sources and focused on the insights they provide for gene structure in the genome of this recently sequenced model system. The genome had initially been annotated by use of computational gene model prediction algorithms. A large fraction of these predicted genes were recovered in the transcriptome when the reads were mapped to the genome and appropriately filtered and analyzed. However, in a manually curated subset, we discovered that more than half the computational gene model predictions were imperfect, containing errors such as missing exons, prediction of nonexistent exons, erroneous intron/exon boundaries, fusion of adjacent genes, and prediction of multiple genes from single genes. The transcriptome data have been used to provide a systematic upgrade of the gene model predictions throughout the genome, very greatly improving the research usability of the genomic sequence. We have constructed new public databases that incorporate information from the transcriptome analyses. The transcript-based gene model data were used to define average structural parameters for S. purpuratus protein-coding genes. In addition, we constructed a custom sea urchin gene ontology, and assigned about 7000 different annotated transcripts to 24 functional classes. Strong correlations became evident between given functional ontology classes and structural properties, including gene size, exon number, and exon and intron size.
Neutron protein crystallography at ultra-low (<15 K) temperatures
Authors: Myles Dean A. A. , Dauvergne François , Blakeley Matthew P. , Meilleur Flora
Published: June 2012

Techniques and equipment have been developed that enable large protein crystals (1–6 mm3) flash-cooled in liquid nitrogen at 77 K to be transferred and mounted on a liquid helium Displex cryorefrigerator and cooled to temperatures down to 15 K for accurate neutron diffraction analysis. In preliminary experiments, it was possible to collect high-quality high-resolution neutron diffraction data to 1.55 Å resolution from several large crystals of triclinic hen egg white lysozyme cooled to 15 K. This enabled the subsequent cryogenic analysis of two further proteins, rubredoxin and concanavalin A, at 1.7 and 2.5 Å, respectively, demonstrating the generality of the approach. The ability to flash-cool such large crystals for cryogenic neutron analysis should significantly broaden the range of scientific questions examined by neutron protein crystallography, allowing the analysis of structures and transitions as a function of temperature and enabling freeze-trapped capture of kinetic intermediates in protein systems.
A novel event correlation scheme for X-ray photon correlation spectroscopy
Authors: Chushkin Y. , Caronna C. , Madsen A.
Published: June 2012

X-ray photon correlation spectroscopy (XPCS) was employed to measure the time-dependent intermediate scattering function in an organic molecular glass former. Slow translational dynamics were probed in the glassy state and the correlation functions were calculated from two-dimensional speckle patterns recorded by a CCD detector. The image frames were analysed using a droplet algorithm together with an event correlation scheme. This method provides results analogous to standard intensity correlation algorithms but is much faster, hence addressing the recurrent problem of insufficient computing power for online analysis in XPCS. The event correlator has a wide range of potential future applications at synchrotrons and free-electron laser sources.
Improved response with post‐ASCT consolidation by low dose thalidomide, cyclophosphamide and dexamethasone as first line treatment for multiple myeloma
Authors: Rabin Neil , Percy Laura , Khan Iftekhar , Quinn John , D'Sa Shirley , Yong Kwee L.
Published: June 2012

The use of consolidation or maintenance to improve disease response, and hence clinical outcome, following autologous stem cell transplantation (ASCT) remains the subject of intense clinical research. We carried out a single‐arm study to assess the toxicity and efficacy of a short block of consolidation therapy with cyclophosphamide, low dose thalidomide and dexamethasone (CTD) in patients within 6 months following ASCT, as part of frontline therapy for symptomatic multiple myeloma. Forty‐five patients who had not progressed were enrolled on the study, and 43 completed treatment on protocol. This regimen was well tolerated soon after ASCT, with only grade 1/2 toxicity apart from neutropenia, and no long‐term sequelae. Importantly, CTD consolidation improved the depth of response in treated patients, increasing the complete/very good partial response rate from 44% at 3 months, to 72% at 12 months, which was significantly higher compared with a historical group of control patients (P = 0·002). There was a trend to longer progression‐free survival that favoured the study group. Consolidation therapy did not adversely affect subsequent disease response to salvage therapies at relapse. We conclude that CTD consolidation may be a useful, non‐toxic and cost‐effective strategy to deepen disease response following ASCT, and deserves further study in a randomized trial.
Associations between testosterone, bone mineral density, vitamin D and semen quality in fertile and infertile Chinese men
Authors: Yang B. , Sun H. , Wan Y. , Wang H. , Qin W. , Yang L. , Zhao H. , Yuan J. , Yao B.
Published: June 2012

Testosterone (T) and vitamin D (VD) interact in androgen deficient men, however, this interaction and subsequent semen quality and bone mineral density (BMD) status is not clear in infertile men. Our objective was to investigate T, VD, semen quality, BMD and their relationships in Chinese infertile men. We conducted a cross‐sectional study of 559 men aged 20–40 years, including 195 fertile men, 9 infertile men with known risk factors for osteoporosis (WR) and 355 infertile men without known risk factors for osteoporosis (WOR). WOR infertile men constituted 314 oligo‐, astheno‐, teratospermic or normospermic infertile men (OATN men) and 41 non‐obstructive azoospermic men (NOA men). Differences of parameters were assessed, and the relationships were adjusted by multiple linear regression. WOR infertile men had significantly lower T, lumbar spine and total hip BMD than fertile men (all p < 0.05). Bioavailable T (Bio‐T) and 25‐hydroxyvitamin D [25(OH)D] were independent determinants of BMD in WOR infertile men (all p < 0.01) but not in fertile men. After stratifying Bio‐T, WOR infertile men had lower BMD than fertile men (all p < 0.05) in low Bio‐T subgroups (Bio‐T ≤ 11.6 nmol/L), but not high Bio‐T subgroups (Bio‐T > 11.6 nmol/L). 25(OH)D was an independent determinant of sperm motility and morphology in WOR OATN men (all p < 0.05), with only borderline significance in fertile men(motility: p = 0.047; morphology: p = 0.056). T determined sperm concentration (square root) and morphology in WOR OATN men (all p < 0.001). No correlations between T and 25(OH)D were found in all groups. We suggest that infertile men have lower T and BMD than fertile men. 25(OH)D and T were associated with low BMD and poor semen quality in infertile men.
Identification of a novel HLA‐C*01:61 allele by polymerase chain reaction sequence‐based typing in a Chinese leukemia patient
Authors: Tao S.‐D. , Zhang W. , He J. , Zhu F.‐M. , Lv H.‐J.
Published: June 2012

HLA‐C*01:61 allele was different from HLA‐C*01:02:01 by a single nucleotide substitution at position 303 C>A.
Functional Morphology of the Aardvark Tail
Authors: Endo H. , Mori K. , Koyabu D. , Kawada S. , Komiya T. , Itou T. , Koie H. , Kitagawa M. , Sakai T.
Published: June 2012

The musculoskeletal system of the aardvark (Orycteropus afer) tail was morphologically examined in two adult specimens. The tail musculature comprised three muscular groups, viz. a dorsal sacrocaudal system that consisted of the irregularly oriented Musculus sacrocaudalis dorsalis medialis and M. sacrocaudalis dorsalis lateralis, a lateral inter‐vertebral connecting system, and a ventral sacrocaudal system characterized by the thick M. sacrocaudalis ventralis lateralis and M. sacrocaudalis ventralis medialis. Both the dorsal and ventral systems possessed large tendon groups that strengthened the tail structure. Computed tomography (CT) examination showed the presence of large but homogeneous cartilaginous inter‐vertebral discs, whereas V‐shaped bones were situated at the ventral aspect of the caudal vertebrae at the level of the inter‐vertebral discs. CT visualization of the tendons and V‐shaped bones in various tail positions suggested that these structures contribute to the tunnel digging action by bearing the trunk weight and lending force when the aardvark are displacing the soil by means of the forelimbs.
Significance of endothelial dysfunction in sleep‐related breathing disorder
Authors: LUI MACY MEI‐SZE , LAM DAVID CHI‐LEUNG , IP MARY SAU‐MAN
Published: June 2012

The endothelium functions not only as a semi‐selective barrier between body tissue and circulation; it also plays an active role in the maintenance of a healthy vasculature. Endothelial dysfunction is increasingly found to play a pivotal role in the pathogenesis of atherosclerosis. Impaired endothelium‐dependent vasodilation, as a marker of endothelial dysfunction, predates and predicts cardiovascular disease. Endothelial dysfunction is thought to result from oxidative stress, inflammatory gene activation and cytokine cascade, as well as impairment of endothelial repair mechanisms. In the context of sleep‐related breathing disorders, obstructive sleep apnoea (OSA) is postulated to contribute independently to cardiovascular morbidity and mortality. Thus, endothelial dysfunction is an important target of research in vascular pathogenesis and also serves as an intermediary outcome indicator in clinical trials evaluating cardiovascular sequelae in OSA. Basic or translational studies have identified cellular and molecular mechanisms of potential relevance to endothelial dysfunction in OSA, while epidemiological or clinical studies have shown endothelial dysfunction attributable to sleep‐disordered breathing, which could improve with effective treatment of OSA. Endothelial dysfunction is poised to serve as a call for timely intervention with possibility of halting or even reverting vascular injury in sleep‐related breathing disorders. Much remains to be explored about the complex pathways of endothelial dysfunction and its clinical manifestations in subjects with OSA, which are likely to involve multiple contributing factors. Evidence‐based information will allow us to construct the framework for guiding individualized clinical management and public health strategies for OSA, as well as cardiometabolic diseases.
Cortical circuit dysfunction and cognitive deficits in schizophrenia – implications for preemptive interventions
Authors: Lewis David A.
Published: June 2012

Schizophrenia is a devastating disorder that is common, usually chronic, frequently associated with substantial co‐morbidity for addictive and medical disorders and, as a consequence, very costly in both personal and economic terms. At present, no proven means for preventing or modifying the course of the illness exist. This review discusses evidence supporting the ideas that: (i) impairments in certain cognitive processes are the core feature of schizophrenia; (ii) these cognitive impairments reflect abnormalities in specific cortical circuits; and (iii) these circuitry abnormalities arise during childhood–adolescence. The implications of these findings for the development and implementation of safe, preemptive, disease‐modifying interventions in individuals at high risk for a clinical diagnosis of schizophrenia are considered.
Cognitive dysfunction and depression in Parkinson’s disease: what can be learned from rodent models?
Authors: Lindgren Hanna S. , Dunnett Stephen B.
Published: June 2012

Parkinson’s disease (PD) has for decades been considered a pure motor disorder and its cardinal motor symptoms have been attributed to the loss of dopaminergic (DAergic) neurons in the substantia nigra pars compacta and to nigral Lewy body pathology. However, there has more recently been a shift in the conceptualization of the disease, and its pathological features have now been recognized as involving several other areas of the brain and indeed even outside the central nervous system. There are a corresponding variety of intrinsic non‐motor symptoms such as autonomic dysfunction, cognitive impairment, sleep disturbances and neuropsychiatric problems, which cannot be explained exclusively by nigral pathology. In this review, we will focus on cognitive impairment and affective symptoms in PD, and we will consider whether, and how, these deficits can best be modelled in rodent models of the disorder. As only a few of the non‐motor symptoms respond to standard DA replacement therapies, the quest for a broader therapeutic approach remains a major research effort, and success in this area in particular will be strongly dependent on appropriate rodent models. In addition, better understanding of the different models, as well as the advantages and disadvantages of the available behavioural tasks, will result in better tools for evaluating new treatment strategies for PD patients suffering from these neuropsychological symptoms.
Microbiology and proteomics, getting the best of both worlds!
Authors: Armengaud Jean
Published: June 2012

High‐throughput identification of proteins with the latest generation of hybrid high‐resolution mass spectrometers is opening new perspectives in microbiology. I present, here, an overview of tandem mass spectrometry technology and bioinformatics for shotgun proteomics that make 2D‐PAGE approaches obsolete. Non‐labelling quantitative approaches have become more popular than labelling techniques on most proteomic platforms because they are easier to carry out while their quantitative outcome is rather robust. Parameters for recording mass spectrometry data, however, need to be chosen carefully and statistics to assess the confidence of the results should not be neglected. Interestingly, next‐generation sequencing methodologies make any microbial model quickly amenable to proteomics, leading to the documentation of a wide range of organisms from diverse environments. Some recent discoveries made using microbial proteomics have challenged some biological dogma, such as: (i) initiation of the translation does not occur predominantly from ATG codons in some microorganisms, (ii) non‐canonical initiation codons are used to regulate the production of specific but important proteins and (iii) a gene may code for multiple polypeptide species, heterogeneous in terms of sequences. Microbial diversity and microbial physiology can now be revisited by means of exhaustive comparative proteomic surveys where thousands of proteins are detected and quantified. Proteogenomics, consisting of better annotating of genomes with the help of proteomic evidence, is paving the way for integrated multi‐omic approaches in microbiology. Finally, meta‐proteomic tools and approaches are emerging for tackling the high complexity of the microbial world as a whole, opening new perspectives for assessing how microbial communities function.
Diabetic Medicine introduces an online option for publication
Authors: Hitman G. A.
Published: June 2012

Diabet. Med. 29, 835 (2012)
Global marine yield halved as fishing intensity redoubles
Authors: Watson Reg A , Cheung William W L , Anticamara Jonathan A , Sumaila Rashid U , Zeller Dirk , Pauly Daniel
Published: June 2012

There is widespread concern and debate about the state of global marine resources and the ecosystems supporting them, notably global fisheries, as catches now generally stagnate or decline. Many fisheries are not assessed by standard stock assessment methods including many in the world's most biodiverse areas. Though simpler methods using widely available catch data are available, these are often discounted largely because data on fishing effort that contributed to the changes in catches are mostly not considered. We analyse spatial and temporal patterns of global fishing effort and its relationship with catch to assess the status of the world's fisheries. The study reveals that fleets now fish all of the world's oceans and have increased in power by an average of 10‐fold (25‐fold for Asia) since the 1950s. Significantly, for the equivalent fishing power expended, landings from global fisheries are now half what they were a half‐century ago, indicating profound changes to supporting marine environments. This study provides another dimension to understand the global status of fisheries.
KEYNES' WAGE–PRICE DYNAMICS
Authors: Dos Santos Ferreira Rodolphe , Michel Philippe
Published: June 2012

The paper presents a simple loglinear macroeconomic model designed to discuss the essentials of Keynes' dynamic analysis in the General Theory and in the Treatise on Money. The model has a conventional static Aggregate Demand—Aggregate Supply block plus a three‐dimensional dynamic system involving the money wage and the expected level and rate of change of the output price. It illustrates Keynes' ideas, in particular on the nature of unemployment and on the stabilizing nature of money (as opposed to real) wage stickiness. It also allows to reconcile with empirical observations Keynes' (false) conjecture on the negative correlation of money and real wages.
Interaction of mineral salts with the skin: a literature survey
Authors: Polefka T. G. , Bianchini R. J. , Shapiro S.
Published: June 2012

Synopsis

There is growing scientific evidence that the health, well‐being and the attractiveness of the skin are strongly influenced by nutrition. Consumers recognize this and have supported the creation of a global cosmeceuticals market estimated in 2010 at $27.2 billion. Early in 2011, the US Department of Health and Human Services and Department of Agriculture issued the Dietary Guidelines for Americans, 2010. Twelve vitamins and nine minerals were recognized as essential. The minerals include calcium, copper, iron, magnesium, phosphorus, selenium, zinc, potassium and sodium. Although the topical benefits of several minerals such as zinc, magnesium and iron are recognized and, in some cases, approved by the FDA, the topical benefits of the others to the skin are largely unexplored and unexploited. This review attempts to summarize what has been published in the literature on the interactions of the eight of the nine essential elements with the skin.
Dysautonomia after pediatric brain injury
Authors: KIRK KATHERINE A , SHOYKHET MICHAEL , JEONG JONG H , TYLER‐KABARA ELIZABETH C , HENDERSON MARYANNE J , BELL MICHAEL J , FINK ERICKA L
Published: June 2012

Aim  Dysautonomia after brain injury is a diagnosis based on fever, tachypnea, hypertension, tachycardia, diaphoresis, and/or dystonia. It occurs in 8 to 33% of adults with brain injury and is associated with poor outcome. We hypothesized that children with brain injury with dysautonomia have worse outcomes and prolonged rehabilitation, and sought to determine the prevalence of dysautonomia in children and to characterize its clinical features.

Method  We developed a database of children (n=249, 154 males, 95 females; mean [SD] age 11 years 10 months [5y 7mo]) with traumatic brain injury, cardiac arrest, stroke, infection of the central nervous system, or brain neoplasm admitted for rehabilitation to The Children’s Institute of Pittsburgh between 2002 and 2009. Dysautonomia diagnosis, injury type, clinical signs, length of stay, and Functional Independence Measure for Children (WeeFIM) testing were extracted from medical records, and analysed for differences between groups with and without dysautonomia.

Results  Dysautonomia occurred in 13% of children with brain injury (95% confidence interval 9.3–18.0%), occurring in 10% after traumatic brain injury and 31% after cardiac arrest. The combination of hypertension, diaphoresis, and dystonia best predicted a diagnosis of dysautonomia (area under the curve=0.92). Children with dysautonomia had longer stays, worse WeeFIM scores, and improved less on the score’s motor component (all p≤0.001).

Interpretation  Dysautonomia is common in children with brain injury and is associated with prolonged rehabilitation. Prospective study and standardized diagnostic approaches are needed to maximize outcomes.
Cerebral palsy: the central nervous system informs the visual system
Authors: GOOD WILLIAM V
Published: June 2012

This commentary is on the original article by Fazzi et al. on pages730‐736 of this issue
Inhibition of lysosome degradation on autophagosome formation and responses to GMI, an immunomodulatory protein from Ganoderma microsporum
Authors: Hsin I‐Lun , Sheu Gwo‐Tarng , Jan Ming‐Shiou , Sun Hai‐Lun , Wu Tzu‐Chin , Chiu Ling‐Yen , Lue Ko‐Huang , Ko Jiunn‐Liang
Published: June 2012

BACKGROUND AND PURPOSE Autophagic cell death is considered a self‐destructive process that results from large amounts of autophagic flux. In our previous study, GMI, a recombinant fungal immunomodulatory protein cloned from Ganoderma microsporum, induced autophagic cell death in lung cancer cells. The aim of this study was to examine the role of autophagosome accumulation in GMI‐mediated cell death.

EXPERIMENTAL APPROACH Western blot analysis, flow cytometry and confocal microscopy were used to evaluate the effects of different treatments, including silencing of ATP6V0A1 by use of short hairpin RNAi, on GMI‐mediated cell death, lung cancer cell viability and autophagosome accumulation in vitro.

KEY RESULTS Lysosome inhibitors bafilomycin‐A1 and chloroquine increased GMI‐mediated autophagic cell death. GMI and bafilomycin‐A1 co‐treatment induced the accumulation of large amounts of autophagosomes, but did not significantly induce apoptosis. GMI elicited autophagy through the PKB (Akt)/mammalian target of rapamycin signalling pathway. Silencing of ATP6V0A1, one subunit of vesicular H+‐ATPases (V‐ATPases) that mediates lysosome acidification, spontaneously induced autophagosome accumulation, but did not affect lysosome acidity. GMI‐mediated autophagosome accumulation and cytotoxicity was increased in shATP6V0A1 lung cancer cells. Furthermore, ATP6V0A1 silencing decreased autophagosome and lysosome fusion in GMI‐treated CaLu‐1/GFP‐LC3 lung cancer cells.

CONCLUSION AND IMPLICATIONS We demonstrated that autophagosome accumulation induces autophagic cell death in a GMI treatment model, and ATP6V0A1 plays an important role in mediating autophagosome‐lysosome fusion. Our findings provide new insights into the mechanisms involved in the induction of autophagic cell death.