bluuebunny/crossref_metadata_2025 huggingface dataset:
Docking and QSAR Studies of Camptothecin Derivatives as Inhibitor of DNA Topoisomerase-I
Authors: Yadav Dharmendra , Khan Feroz , Srivastava Santosh
Published: April 2011

Camptothecin (CPT) is a cytotoxic quinoline alkaloid which inhibits the DNA enzyme Topoisomerase-I (Topo-I) and has shown remarkable anticancer activity in preliminary clinical trials. The major limitation is its low solubility and high adverse reaction. In the studied work, we performed molecular docking of CPT derivatives against Topo-I and developed the quantitative structure activity relationship (QSAR) model for anticancer activity screening. For QSAR, we used CPT and other anticancer drugs with its IC50 values. We used a total of forty seven anticancer drugs as training set and eight compounds as test set and thirty derivatives of CPT as query set. Total of fifty two chemical descriptors were used for the quantitative data calculation. Only four showed good correlation with the experimental activity. Forward feed regression method was used for development of multiple linear regression (MLR) QSAR model. Model showed acceptable regression coefficient (r2) 0.89 (i.e., 89% of correlation) and cross validation coefficient (rCV2) 0.86 (i.e., 86 % of prediction accuracy). After drug likeness test, ten compounds namely, MSB3a, MSB3b, MSB19, MSB22L, MSB22M, MSB22O, MSB22R, MSB25D, MSB37G and MSB39D, showed promising predicted anticancer activity and drug likeness properties. Out of ten, only six compounds namely, MSB19, MSB22L, MSBM, MSB22O, MSB22R and MSB37D indicate two times more activity than the parent CPT compound. In molecular docking studies, all the identified active CPT derivatives showed high binding affinity with Topo-I. QSAR study indicates that connectivity index, electron affinity, mol.wt. & ether group count highly contribute to inhibitory activity of CPT derivatives. These results can offer useful references for directing the molecular design of Topo-I inhibitor with improved anticancer activity.
Molecular crowding defines a common origin for the Warburg effect in proliferating cells and the lactate threshold in muscle physiology
Authors: Vazquez Alexei
Published: April 2011

Aerobic glycolysis is a seemingly wasteful mode of ATP production that is seen both in rapidly proliferating mammalian cells and highly active contracting muscles, but whether there is a common origin for its presence in these widely different systems is unknown. To study this issue, here we develop a model of human central metabolism that incorporates a solvent capacity constraint of metabolic enzymes and mitochondria, accounting for their occupied volume densities, while assuming glucose and/or fatty acid utilization. The model demonstrates that activation of aerobic glycolysis is favored above a threshold metabolic rate in both rapidly proliferating cells and heavily contracting muscles, because it provides higher ATP yield per volume density than mitochondrial oxidative phosphorylation. In the case of muscle physiology, the model also predicts that before the lactate switch, fatty acid oxidation increases, reaches a maximum, and then decreases to zero with concomitant increase in glucose utilization, in agreement with the empirical evidence. These results are further corroborated by a larger scale model, including biosynthesis of major cell biomass components. The larger scale model also predicts that in proliferating cells the lactate switch is accompanied by activation of glutaminolysis, another distinctive feature of the Warburg effect. In conclusion, intracellular molecular crowding is a fundamental constraint for cell metabolism in both rapidly proliferating- and non-proliferating cells with high metabolic demand. Addition of this constraint to metabolic flux balance models can explain several observations of mammalian cell metabolism under steady state conditions.
Clays: Colloidal Properties in Nanodomain
Authors: Mukhopadhyay Siddhartha
Published: April 2011

The ever-growing application of clays in nanotechnology rests on fundamental principles of colloid chemistry. They make soils as nature’s great electrostatic chemical reactor. Highly anisotropic and often irregular particle shape, broad particle size distribution, different types of charges within the unit cells, heterogeneity of layer charges, pronounced CEC, dis-articulation and flexibility of layers, and different modes of aggregation make clays different from other colloidal materials. Their inseparable association with the genesis of life on Earth and evolutionary diversification of Neoproterozoic life is a safety-belt of nanotechnology.Nanotechnology promises to be the greatest technological breakthrough in history, doing for our control of matter what computers did for our control of information. The origins of nanoscience can be traced to clay mineralogy and crystallography when it was discovered that clay minerals were crystalline and of micrometer size. The unit cell dimensions of clay minerals are in nanometer scale in all three axes (x, y, and z). The advantages of clays are: (i) their ordered arrangements, (ii) their large adsorption capacity, (iii) their shielding against sunlight (ultraviolet radiation), (iv) their ability to concentrate organic chemicals, and (v) their ability to serve as polymerization templates. Clays protected organic matter from reoxygenation during the late Precambrian period, allowing a corresponding quantity of O2 to accumulate in the environment. The inseparable association of clays with lifeforms makes them most desirable in manufacturing nanoparticles. Clays have been extensively used in industry, but as concern for environmental sustainability grows, clay minerals find new takers from all conceivable forms of industries. Nanotechnology literature is flooded with clay-polymers for their possible use in high strength material manufacturing, for ecological life support system, removal of contaminants from water and wastes, and as catalysts in chemical reactions to reduce energy consumption.
Maximization of learning speed in motor cortex due to neuron redundancy
Authors: Takiyama Ken , Okada Masato
Published: April 2011

Many kinds of redundancies play important roles in the motor system. Many combinations of muscle activity can generate an identical movement. One of the functional and computational roles of this muscle redundancy is to control joint impedance for stabilizing movements against applied external perturbation. Many combinations of joint angles can yield an identical fingertip position. A functional and computational role of this kinematic redundancy is to ensure motor accuracy, if a joint angle is perturbed, by adjusting redundant ones. Neurons are overwhelmingly more numerous than muscles in our motor system. However, an open question remains as to what the functional and computational roles of this neuron redundancy are. To generate desired motor commands, our motor system adapts to changes in both the internal and external environment, caused by muscle fatigue, force fields, etc. Faster learning is more desirable than slower learning because accumulated error can be minimized. Our analysis on a neural network model, assuming visuomotor or force field adaptation, revealed that learning speed reaches its maximum value if the model includes sufficient neuron redundancy. We subsequently ran numerical simulations of more biologically plausible neural network models. The results suggest that neuron redundancy accelerates learning speed even if the models include recurrent connections, a two-layer structure, or a skewed bimodal distribution of preferred directions. Neuron redundancy also yields the equivalence between a learning rule of synaptic weights and a model for sensorimotor learning, which is based on the results of behavioral experiments. These results suggest that neuron redundancy contributes to maximizing learning speed and also that the learning curves observed in behavioral experiments are tuned to be as fast as possible.
Genetic differentiation of wild and managed Coffea arabica populations in Afromontane rainforest fragments in SW Ethiopia
Authors: Aerts Raf , Berecha Gezahegn , Gijbels Pieter , Van Glabeke Sabine , Vandepitte Katrien , Muys Bart , Roldán-Ruiz Isabel , Honnay Olivier
Published: April 2011

*1.* Coffea arabica L. has its origin and centre of diversity in the Afromontane rainforests of southwestern Ethiopia. Deforestation, habitat fragmentation and forest degradation threaten this wild coffee gene pool, which is vital to global coffee cultivation.*2.* We investigated genetic variation and diversity within and between eleven coffee stands across a gradient of increasing forest management intensity (‘forest coffee’, unmanaged large continuous forest vs. ‘semi-forest coffee’, managed, small fragments) using two multiplex panels of five microsatellite markers each. We used analysis of molecular variance (AMOVA) to partition total genetic diversity and applied a Bayesian model-based cluster method to infer population structure.*3.* Genetic variability was larger within (72%) than between (21%) stands. There was a significant differentiation between three wild coffee genotypes in the least disturbed forest and a single genotype prevailing in the semi-forest coffee system. Managed populations were closely allied to local coffee cultivars indicating an effect of local selection, but measures of neutral genetic diversity (Ne, I, He, MV) did not differ significantly between management systems.*4.* Despite severe forest fragmentation, we found no evidence for genetic erosion in C. arabica, possibly because traditional Ethiopian coffee cultivation involves collecting, exchanging and replanting coffee. Nevertheless, this poses a threat to wild coffee populations because they are replaced by (or exposed to genetic exchange with) genotypes imported from other areas and that are preferred by local farmers due to specific characteristics. In-situ conservation efforts must therefore focus on avoiding intensification of coffee production in forest coffee systems.
CloVR-Metagenomics: Functional and taxonomic microbial community characterization from metagenomic whole-genome shotgun (WGS) sequences – standard operating procedure, version 1.0
Authors: White James , Arze Cesar , Matalka Malcolm , Team The CloVR , Angiuoli Samuel , Fricke W. Florian
Published: April 2011

The CloVR-Metagenomics pipeline employs several well-known tools and protocols for the analysis of metagenomic whole-genome shotgun (WGS) sequence datasets:A) UCLUST [1] – a C++-based software package for clustering redundant DNA sequences and removing artificial 454 replicates [1];B) BLASTX and BLASTN [2] for functional and taxonomic assignment of sequences, respectively;C) Metastats [3] and custom R scripts to generate additional statistical and graphical evaluation.The CloVR-Metagenomics pipeline accepts as input multiple fasta files (1 sample per file) and a corresponding tab-delimited metadata file that specifies features associated with the samples, which are used for comparative analysis. This protocol is available in CloVR beta version 0.5 and 0.6.
Highly enantioselective zinc/BINOL-catalyzed alkynylation of α-ketoimine ester: a new entry to optically active quaternary α-CF3 α-amino acids
Authors: Huang Gaochao , Yang Jie , Zhang Xingang
Published: April 2011

An effective method for highly enantioselective alkynylation of ketoimine (α-trifluoromethyl ketoimine ester) has been developed via a zinc/BINOL catalyzed process.
Fine tuning of the catalytic effect of a metal-free porphyrin on the homogeneous oxygenreduction
Authors: Trojánek Antonín , Langmaier Jan , Šebera Jakub , Záliš Stanislav , Barbe Jean-Michel , Girault Hubert H. , Samec Zdeněk
Published: April 2011

The reported catalytic effect of a metal-free porphyrin on the homogeneous dioxygen reduction is related to the competitive binding of dioxygen and the counteranion to the protonated free porphyrin base.
Does Fiscal Decentralisation Strengthen Social Capital? Cross-Country Evidence and the Experiences of Brazil and Indonesia
Authors: de Mello Luiz
Published: April 2011

With this paper I test the hypothesis that, by giving people more voice in the government decision-making process, fiscal decentralisation fosters social capital, measured in terms of interpersonal trust. Empirical evidence based on World Values Survey data and seemingly unrelated probit estimations for a cross-section of countries suggests that people living in federal and decentralised countries find it more important to have a voice in government decisions than their counterparts living in unitary and centralised countries. Provoice attitudes are, in turn, associated with greater social capital. The cross-country estimations are complemented by country-specific regressions for Brazil and Indonesia on account of these countries' experiences with fiscal decentralisation. The results show that the cohorts of individuals that have been exposed to decentralisation are in general more provoice (and trustful of strangers in the case of Brazil) than their counterparts that have not been exposed to decentralisation. These findings are not driven by the effects of political liberalisation on people's attitudes towards the importance of having a voice in government decisions and interpersonal trust.
Decentralization and the Nationalization of Party Systems
Authors: Lago-Peñas Ignacio , Lago-Peñas Santiago
Published: April 2011

On the basis of a sample of 227 elections in seventeen Western European countries over the period 1945–98, we examine to what extent party systems are shaped by fiscal and political decentralization. With the exception of a few special cases, empirical evidence does not support the existence of a robust relationship between the degree of decentralization and the nationalization of party systems.
Decentralization and Voter Turnout
Authors: Blais André , Anduiza Eva , Gallego Aina
Published: April 2011

With this paper we study the impact of decentralization on turnout. We test the hypotheses that decentralization increases turnout in subnational elections, lowers participation in national elections, and reduces the gap between regional and national arenas. A comparative cross-national analysis does not show any significant effect of decentralization on turnout in national elections. But we take a closer look at two countries, Canada and Spain, where fiscal decentralization has taken place during the past decades. In both countries the empirical evidence suggests that decentralization has contributed to reducing the turnout gap between regional and national elections.
The Consequences of Fiscal Decentralization on Poverty and Income Equality
Authors: Sepulveda Cristian F , Martinez-Vazquez Jorge
Published: April 2011

Many countries around the world are currently pursuing policies for poverty reduction and the improvement of income distribution, and most of them are also implementing fiscal decentralization reforms. Although, separately, fiscal decentralization, poverty, and the distribution of income have been the subjects of extensive theoretical and empirical research, to date we have little understanding of what may be the impact of fiscal decentralization on poverty and inequality. We set out to shed some light on those relationships. We describe the possible channels through which fiscal decentralization might affect poverty and income inequalities and carry out an empirical analysis using panel data for a large number of countries. We find that fiscal decentralization may have significant effects on poverty and inequality. In particular, fiscal decentralization appears to lead to increases in the poverty measures we use, but it also appears to reduce income inequality if the general government represents a significant share of the economy (20% or more).
N-terminal domain of αB-crystallin provides a conformational switch for multimerization and structural heterogeneity
Authors: Jehle Stefan , Vollmar Breanna S. , Bardiaux Benjamin , Dove Katja K. , Rajagopal Ponni , Gonen Tamir , Oschkinat Hartmut , Klevit Rachel E.
Published: April 2011

The small heat shock protein (sHSP) αB-crystallin (αB) plays a key role in the cellular protection system against stress. For decades, high-resolution structural studies on heterogeneous sHSPs have been confounded by the polydisperse nature of αB oligomers. We present an atomic-level model of full-length αB as a symmetric 24-subunit multimer based on solid-state NMR, small-angle X-ray scattering (SAXS), and EM data. The model builds on our recently reported structure of the homodimeric α-crystallin domain (ACD) and C-terminal IXI motif in the context of the multimer. A hierarchy of interactions contributes to build multimers of varying sizes: Interactions between two ACDs define a dimer, three dimers connected by their C-terminal regions define a hexameric unit, and variable interactions involving the N-terminal region define higher-order multimers. Within a multimer, N-terminal regions exist in multiple environments, contributing to the heterogeneity observed by NMR. Analysis of SAXS data allows determination of a heterogeneity parameter for this type of system. A mechanism of multimerization into higher-order asymmetric oligomers via the addition of up to six dimeric units to a 24-mer is proposed. The proposed asymmetric multimers explain the homogeneous appearance of αB in negative-stain EM images and the known dynamic exchange of αB subunits. The model of αB provides a structural basis for understanding known disease-associated missense mutations and makes predictions concerning substrate binding and the reported fibrilogenesis of αB.
Late Carboniferous paleoichnology reveals the oldest full-body impression of a flying insect
Authors: Knecht Richard J. , Engel Michael S. , Benner Jacob S.
Published: April 2011

Insects were the first animals to evolve powered flight and did so perhaps 90 million years before the first flight among vertebrates. However, the earliest fossil record of flying insect lineages (Pterygota) is poor, with scant indirect evidence from the Devonian and a nearly complete dearth of material from the Early Carboniferous. By the Late Carboniferous a diversity of flying lineages is known, mostly from isolated wings but without true insights into the paleoethology of these taxa. Here, we report evidence of a full-body impression of a flying insect from the Late Carboniferous Wamsutta Formation of Massachusetts, representing the oldest trace fossil of Pterygota. Through ethological and morphological analysis, the trace fossil provides evidence that its maker was a flying insect and probably was representative of a stem-group lineage of mayflies. The nature of this current full-body impression somewhat blurs distinctions between the systematics of traces and trace makers, thus adding to the debate surrounding ichnotaxonomy for traces with well-associated trace makers.
Ergodic and nonergodic processes coexist in the plasma membrane as observed by single-molecule tracking
Authors: Weigel Aubrey V. , Simon Blair , Tamkun Michael M. , Krapf Diego
Published: April 2011

Diffusion in the plasma membrane of living cells is often found to display anomalous dynamics. However, the mechanism underlying this diffusion pattern remains highly controversial. Here, we study the physical mechanism underlying Kv2.1 potassium channel anomalous dynamics using single-molecule tracking. Our analysis includes both time series of individual trajectories and ensemble averages. We show that an ergodic and a nonergodic process coexist in the plasma membrane. The ergodic process resembles a fractal structure with its origin in macromolecular crowding in the cell membrane. The nonergodic process is found to be regulated by transient binding to the actin cytoskeleton and can be accurately modeled by a continuous-time random walk. When the cell is treated with drugs that inhibit actin polymerization, the diffusion pattern of Kv2.1 channels recovers ergodicity. However, the fractal structure that induces anomalous diffusion remains unaltered. These results have direct implications on the regulation of membrane receptor trafficking and signaling.
Cerebellothalamocortical pathway abnormalities in torsinA DYT1 knock-in mice
Authors: Uluğ Aziz M. , Vo An , Argyelan Miklos , Tanabe Lauren , Schiffer Wynne K. , Dewey Stephen , Dauer William T. , Eidelberg David
Published: April 2011

The factors that determine symptom penetrance in inherited disease are poorly understood. Increasingly, magnetic resonance diffusion tensor imaging (DTI) and PET are used to separate alterations in brain structure and function that are linked to disease symptomatology from those linked to gene carrier status. One example is DYT1 dystonia, a dominantly inherited movement disorder characterized by sustained muscle contractions, postures, and/or involuntary movements. This form of dystonia is caused by a 3-bp deletion (i.e., ΔE) in theTOR1Agene that encodes torsinA. Carriers of the DYT1 dystonia mutation, even if clinically nonpenetrant, exhibit abnormalities in cerebellothalamocortical (CbTC) motor pathways. However, observations in human gene carriers may be confounded by variability in genetic background and age. To address this problem, we implemented a unique multimodal imaging strategy in a congenic line of DYT1 mutant mice that contain the ΔE mutation in the endogenous mouse torsinA allele (i.e., DYT1 knock-in). Heterozygous knock-in mice and littermate controls underwent microPET followed by ex vivo high-field DTI and tractographic analysis. Mutant mice, which do not display abnormal movements, exhibited significant CbTC tract changes as well as abnormalities in brainstem regions linking cerebellar and basal ganglia motor circuits highly similar to those identified in human nonmanifesting gene carriers. Moreover, metabolic activity in the sensorimotor cortex of these animals was closely correlated with individual measures of CbTC pathway integrity. These findings further link a selective brain circuit abnormality to gene carrier status and demonstrate that DYT1 mutant torsinA has similar effects in mice and humans.
Dispersal of
Mycobacterium tuberculosis
via the Canadian fur trade
Authors: Pepperell Caitlin S. , Granka Julie M. , Alexander David C. , Behr Marcel A. , Chui Linda , Gordon Janet , Guthrie Jennifer L. , Jamieson Frances B. , Langlois-Klassen Deanne , Long Richard , Nguyen Dao , Wobeser Wendy , Feldman Marcus W.
Published: April 2011

Patterns of gene flow can have marked effects on the evolution of populations. To better understand the migration dynamics of
Mycobacterium tuberculosis
, we studied genetic data from European
M. tuberculosis
lineages currently circulating in Aboriginal and French Canadian communities. A single
M. tuberculosis
lineage, characterized by the DS6
Quebec
genomic deletion, is at highest frequency among Aboriginal populations in Ontario, Saskatchewan, and Alberta; this bacterial lineage is also dominant among tuberculosis (TB) cases in French Canadians resident in Quebec. Substantial contact between these human populations is limited to a specific historical era (1710–1870), during which individuals from these populations met to barter furs. Statistical analyses of extant
M. tuberculosis
minisatellite data are consistent with Quebec as a source population for
M. tuberculosis
gene flow into Aboriginal populations during the fur trade era. Historical and genetic analyses suggest that tiny
M. tuberculosis
populations persisted for ∼100 y among indigenous populations and subsequently expanded in the late 19th century after environmental changes favoring the pathogen. Our study suggests that spread of TB can occur by two asynchronous processes: (
i
) dispersal of
M. tuberculosis
by minimal numbers of human migrants, during which small pathogen populations are sustained by ongoing migration and slow disease dynamics, and (
ii
) expansion of the
M. tuberculosis
population facilitated by shifts in host ecology. If generalizable, these migration dynamics can help explain the low DNA sequence diversity observed among isolates of
M. tuberculosis
and the difficulties in global elimination of tuberculosis, as small, widely dispersed pathogen populations are difficult both to detect and to eradicate.
Real-time attack on single
Escherichia coli
cells by the human antimicrobial peptide LL-37
Authors: Sochacki Kem A. , Barns Kenneth J. , Bucki Robert , Weisshaar James C.
Published: April 2011

Natural antimicrobial peptides (AMPs) provide prototypes for the design of unconventional antimicrobial agents. Existing bulk assays measure AMP activity but do not provide details of the growth-halting mechanism. We use fluorescence microscopy to directly observe the attack of the human antimicrobial peptide LL-37 on single
Escherichia coli
cells in real time. Our findings strongly suggest that disruption of the cytoplasmic membrane is not the growth-halting mechanism. At 8 μM, LL-37 binding saturates the outer membrane (OM) within 1 min. Translocation across the OM and access to the periplasmic space (5–25 min later) correlates in time with the halting of growth. Septating cells are attacked more readily than nonseptating cells. The halting of growth may occur because of LL-37 interference with cell wall biogenesis. Only well after growth halts does the peptide permeabilize the cytoplasmic membrane to GFP and the small dye Sytox Green. The assay enables dissection of antimicrobial design criteria into two parts: translocation across the OM and the subsequent halting of growth.
FLOWERING LOCUS C (FLC) regulates development pathways throughout the life cycle of
Arabidopsis
Authors: Deng Weiwei , Ying Hua , Helliwell Chris A. , Taylor Jennifer M. , Peacock W. James , Dennis Elizabeth S.
Published: April 2011

FLOWERING LOCUS C (FLC) has a key role in the timing of the initiation of flowering in
Arabidopsis
. FLC binds and represses two genes that promote flowering,
FT
and
SOC1
. We show that FLC binds to many other genes, indicating that it has regulatory roles other than the repression of flowering. We identified 505 FLC binding sites, mostly located in the promoter regions of genes and containing at least one CArG box, the motif known to be associated with MADS-box proteins such as FLC. We examined 40 of the target genes, and 20 showed increased transcript levels in an
flc
mutant compared with the wild type. Five genes showed decreased expression in the mutant, indicating that FLC binding can result in either transcriptional repression or activation. The genes we identified as FLC targets are involved in developmental pathways throughout the life history of the plant, many of which are associated with reproductive development. FLC is also involved in vegetative development, as evidenced by its binding to
SPL15
, delaying the progression from juvenile to adult phase. Some of the FLC target genes are also bound by two other MADS-box proteins, AP1 and SEP3, suggesting that MADS-box genes may operate in a network of control at different stages of the life cycle, many ultimately contributing to the development of the reproductive phase of the plant.
Screening Criteria for Diagnosis of Infantile Feeding Disorders as a Cause of Poor Feeding or Food Refusal
Authors: Levine Arie , Bachar Lea , Tsangen Zili , Mizrachi Avi , Levy Anat , Dalal Ilan , Kornfeld Lia , Levy Yuval , Zadik Zvi , Turner Dan , Boaz Mona
Published: April 2011

Objectives:

Infantile feeding disorders (IFDs) are a common cause of food refusal, failure to thrive, and vomiting, but they may be difficult to diagnose. We have previously identified certain patterns of pathological feeding and behaviors as high‐risk characteristics for IFDs and subsequently developed the diagnostic Wolfson criteria. Here, we evaluate these high‐risk behaviors and prospectively compare the Wolfson criteria with 2 existing classifications of IFD, the Chatoor and that in the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM‐IV).

Patients and Methods:

Infants and young children referred for food refusal were invited to participate by completing a feeding pattern questionnaire. Following physicians' interview and examination, patients were scored by all 3 criteria and enrolled in a structured treatment program for IFD. Infants whose food refusal was associated with an organic cause served as a comparison group. The ability of the criteria to detect IFD and to predict response to therapy was compared with an intention‐to‐treat analysis.

Results:

Eighty‐five infants with new‐onset IFD and 55 controls were included. The Wolfson criteria, Chatoor, and DSM‐IV accurately diagnosed 100%, 77%, and 56% of the patients with IFD, respectively. Anticipatory gagging occurred in 47% of the children with IFD compared to 2% controls (P < 0.001). The response to therapy was similar among the 3 criteria (73–76%), suggesting that the Wolfson criteria did not incorrectly diagnose organic disease as IFD. The 20 infants who were diagnosed as having IFD by Wolfson but not by Chatoor responded equally well (80%) to an IFD treatment program.

Conclusions:

Diagnostic criteria of IFD that are based on food refusal, pathological feeding, and anticipatory gagging have a higher detection rate than the present criteria and are simpler to implement.
Solid‐food Introduction in Infants Diagnosed As Having a Cow's‐milk Protein–induced Enterocolitis
Authors: Beauchamp Josée N , Gaboury Isabelle , Ni Andy , Boland Margaret P , Mack David R
Published: April 2011

Objectives:

In a prior retrospective analysis of 32 infants diagnosed with cow's‐milk protein–induced enterocolitis (CMPIE), gastrointestinal (GI) symptoms were observed with the introduction of milk‐free infant cereal. The aim of this randomized controlled trial was to compare the incidence of new GI symptoms with the introduction of either milk‐free infant rice cereal or carrots as the first complementary food at 6 months of age in infants previously diagnosed as having CMPIE.

Patients and Methods:

Thirty‐nine infants were enrolled in the study. Twenty were randomized to start with pureed carrots and 19 were randomized to start with milk‐free infant rice cereal. GI signs and symptoms developing within 2 weeks were recorded.

Results:

No significant differences were noticed in the incidence of new GI symptoms and the change in the frequency of GI symptoms upon solid‐food introduction, whether it was carrots or milk‐free infant rice cereal. A high overall incidence rate (47%) of new GI symptoms was observed in the whole cohort. The mean number of days for onset of new symptoms was 6. The most common GI signs and symptoms observed were related to alteration of stool characteristics. Breast‐feeding was not shown to have a protective effect on the development of new GI symptoms during solid‐food introduction.

Conclusions:

Many infants with CMPIE will develop GI signs and symptoms following the introduction of solid food, whether milk‐free infant rice cereal or carrots are introduced, and their onset may be delayed.
White Lupin Cluster Root Acclimation to Phosphorus Deficiency and Root Hair Development Involve Unique Glycerophosphodiester Phosphodiesterases
Authors: Cheng Lingyun , Bucciarelli Bruna , Liu Junqi , Zinn Kelly , Miller Susan , Patton-Vogt Jana , Allan Deborah , Shen Jianbo , Vance Carroll P.
Published: April 2011

White lupin (Lupinus albus) is a legume that is very efficient in accessing unavailable phosphorus (Pi). It develops short, densely clustered tertiary lateral roots (cluster/proteoid roots) in response to Pi limitation. In this report, we characterize two glycerophosphodiester phosphodiesterase (GPX-PDE) genes (GPX-PDE1 and GPX-PDE2) from white lupin and propose a role for these two GPX-PDEs in root hair growth and development and in a Pi stress-induced phospholipid degradation pathway in cluster roots. Both GPX-PDE1 and GPX-PDE2 are highly expressed in Pi-deficient cluster roots, particularly in root hairs, epidermal cells, and vascular bundles. Expression of both genes is a function of both Pi availability and photosynthate. GPX-PDE1 Pi deficiency-induced expression is attenuated as photosynthate is deprived, while that of GPX-PDE2 is strikingly enhanced. Yeast complementation assays and in vitro enzyme assays revealed that GPX-PDE1 shows catalytic activity with glycerophosphocholine while GPX-PDE2 shows highest activity with glycerophosphoinositol. Cell-free protein extracts from Pi-deficient cluster roots display GPX-PDE enzyme activity for both glycerophosphocholine and glycerophosphoinositol. Knockdown of expression of GPX-PDE through RNA interference resulted in impaired root hair development and density. We propose that white lupin GPX-PDE1 and GPX-PDE2 are involved in the acclimation to Pi limitation by enhancing glycerophosphodiester degradation and mediating root hair development.
EOBII Controls Flower Opening by Functioning as a General Transcriptomic Switch
Authors: Colquhoun Thomas A. , Schwieterman Michael L. , Wedde Ashlyn E. , Schimmel Bernardus C.J. , Marciniak Danielle M. , Verdonk Julian C. , Kim Joo Young , Oh Youngjoo , Gális Ivan , Baldwin Ian T. , Clark David G.
Published: April 2011

R2R3-MYB transcription factors (TFs) are involved in diverse aspects of plant biology. Recently an R2R3-MYB was identified in Petunia x  hybrida line P720 to have a role in the transcriptional regulation of floral volatile production. We propose a more foundational role for the R2R3-MYB TF EMISSION OF BENZENOIDS II (EOBII). The homolog of EOBII was isolated and characterized from P. x hybrida ‘Mitchell Diploid’ (MD) and Nicotiana attenuata. For both MD and N. attenuata, EOBII transcript accumulates to high levels in floral tissue with maximum accumulation at flower opening. When EOBII transcript levels are severely reduced using a stable RNAi (ir) approach in MD and N. attenuata, ir-EOBII flowers fail to enter anthesis and prematurely senesce. Transcript accumulation analysis demonstrated core phenylpropanoid pathway transcripts and cell wall modifier transcript levels are altered in ir-EOBII flowers. These flowers can be partially complemented by feeding with a sucrose, t-cinnamic acid, and gibberellic acid solution; presumably restoring cellular aspects sufficient for flower opening. Additionally, if ethylene sensitivity is blocked in either MD or N. attenuata, ir-EOBII flowers enter anthesis. These experiments demonstrate one R2R3-MYB TF can control a highly dynamic process fundamental to sexual reproduction in angiosperms: the opening of flowers.
Family Support as a Gang Reduction Measure
Authors: Shute Jon
Published: April 2011

Recent public concern about youth gangs in Britain has prompted a narrow, almost stereotypical, range of US‐derived policy responses. This paper argues that family support is an unexplored but potentially effective gang reduction tool, but in order to overcome persistent concerns regarding misidentification, stigmatic labelling and policy misdirection, programmes must not only be ‘good science’ but also be non‐punitive, acceptable to families and context‐sensitive. Beginning with a discussion of the grounds for intervention, the paper identifies likely barriers from the point of view of the parents of gang members, and from these, derives necessary standards for effective support. The paper describes some promising (‘public health oriented’) and unpromising (‘criminal justice oriented’) programmes, and argues for more ‘gang‐sensitive’ family support and a related research agenda.
Facies characteristics and architecture related to palaeodepth of Holocene fjord–delta sediments
Authors: EILERTSEN RAYMOND S. , CORNER GEOFFREY D. , AASHEIM ODD , HANSEN LOUISE
Published: April 2011

Lithofacies characteristics and depositional geometry of a sandy, prograding delta deposited as part of the Holocene valley‐fill stratigraphy in the Målselv valley, northern Norway, were examined using morpho‐sedimentary mapping, facies analysis of sediments in exposed sections, auger drilling and ground penetrating radar survey. Various lithofacies types record a broad range of depositional processes within an overall coarsening‐upward succession comprising a lowermost prodelta/bottomset unit, an intermediate delta slope/foreset unit containing steeply dipping clinoforms and an uppermost delta plain/topset unit. Bottomset lithofacies typically comprise sand‐silt couplets (tidal rhythmites), bioturbated sands and silts, and flaser and lenticular bedding. These sediments were deposited from suspension fall‐out, partly controlled by tidal currents and fluvial effluent processes. Delta foreset lithofacies comprise massive, inverse graded and normal graded beds deposited by gravity‐driven processes (mainly cohesionless debris flows and turbidity currents) and suspension fall‐out. In places, delta foreset beds show tidal rhythmicity and individual beds can be followed downslope into bottomset beds. Delta plain facies show an upward‐fining succession with trough cross‐beds at the base, followed by planar, laminated and massive beds indicative of a bedload dominated river/distributary system. This study presents a model of deltaic development that can be described with reference to three styles within a continuum related primarily to water depth within a basin of variable geometry: (i) bypass; (ii) shoal‐water; and (iii) deep‐water deltas. Bypass and deep‐water deltas can be considered as end members, whereas shoal‐water deltas are an intermediate type. The bypass delta is characterized by rapid progradation and an absence of delta slope sediments and low basin floor aggradation due to low accommodation space. The shoal‐water delta is characterized by rapid progradation, a short delta slope dominated by gravity‐flow processes and a prodelta area characterized by rapid sea‐floor aggradation due to intense suspension fallout of sandy material. Using tidal rhythmites as time‐markers, a progradation rate of up to 11 m year−1 has been recorded. The deep‐water delta is characterized by a relatively long delta slope dominated by gravity flows, moderate suspension fall‐out and slow sea‐floor aggradation in the prodelta area.
Proteinuric diseases with sodium retention: is plasmin the link?
Authors: Svenningsen Per , Skøtt Ole , Jensen Boye L
Published: April 2011

1. Sodium retention in disease states characterized by proteinuria, such as nephrotic syndrome, pre‐eclampsia and diabetic nephropathy, occurs through poorly understood mechanism(s).

2. In nephrotic syndrome, data from experimental and clinical studies show that the sodium retention originates in the renal cortical collecting duct and involves hyperactivity of the epithelial sodium channel (ENaC).

3. The stimulus for the increased ENaC activity does not appear to involve any of the classical sodium retaining mechanisms, such as the renin–angiotensin–aldosterone system, arginine vasopressin or the sympathetic nervous system.

4. Proteolytic processing of the extracellular domain of γENaC subunit has been shown to stimulate ENaC activity.

5. The serine protease plasmin was recently identified as an ENaC‐activating protease in urine from human nephrotic patients and from the puromycin aminonucleoside (PAN) rat model of nephrotic syndrome.

6. This finding suggests that a defective glomerular filtration barrier allows filtration into the tubular fluid of substances that activate ENaC and enhance sodium reabsorption. This concept might be expanded to other disease states, such as pre‐eclampsia and diabetic nephropathy, which are also characterized by proteinuria and sodium retention.

7. In this review, we will examine the evidence for a role of urinary serine protease activity in the development of sodium and water retention in diseases characterised by proteinuria with a focus on nephrotic syndrome.
Weasels, keys and Thersites
Authors: Beasley A. W.
Published: April 2011

It was the achievement of Andreas Vesalius (1514–1564) to redefine the understanding of human anatomy; and that of Homer was to write the first historical novel. This paper offers a link between the works of these two venturers, by way of an examination of the clinical anatomy of the clavicle.
Change of salivary stress marker concentrations during pregnancy: Maternal depressive status suppress changes of those levels
Authors: Tsubouchi Hiroaki , Nakai Yuichiro , Toda Masahiro , Morimoto Kanehisa , Chang Yang Sil , Ushioda Norichika , Kaku Shoji , Nakamura Takafumi , Kimura Tadashi , Shimoya Koichiro
Published: April 2011

Aim:  The aim of the present study was to show changes in salivary cortisol and chromogranin A/protein concentrations as stress markers during pregnancy and to clarify the effect of chronic stress on stress markers.

Material and Methods:  Salivary samples were collected from 69 pregnant women during pregnancy. Salivary cortisol levels and chromogranin A/protein titers were determined. We surveyed the women's chronic stress using the Zung self‐rating depression scale and General Health Questionnaire‐28.

Results:  Cortisol levels in the saliva of pregnant women showed biphasic change during pregnancy. Chromogranin A/protein levels in the saliva of pregnant women increased in the second and the early third trimesters and decreased to the puerperal period. Salivary cortisol concentrations of the chronic high stress group were significantly lower compared with those of the normal group. Salivary chromogranin A/protein concentrations of the chronic high stress group were also significantly lower than those of the normal group.

Conclusion:  The titration of salivary cortisol concentrations and chromogranin A/protein levels is a useful tool to determine maternal stress levels. The elevation of cortisol and chromogranin A/protein in the saliva was suppressed in the chronic high stress group during pregnancy.
The impact of khat use on East African communities in Melbourne: A preliminary investigation
Authors: FEIGIN ANITA , HIGGS PETER , HELLARD MARGARET , DIETZE PAUL
Published: April 2011

Introduction and Aims. Catha Edulis Forsk (khat) is a plant—reported to have a stimulant effect similar to that of amphetamines—grown and used by eastern African communities worldwide. Khat can be legally consumed in many parts of the world, including Victoria, Australia. Recent concerns have been raised about the social and economic impacts of khat consumption among Victoria's East African community members. This study explores khat use and the social impact it has on East African families and communities in Melbourne, Australia.

Design and Methods. Focus groups and individual interviews were conducted in 2009 with 29 members of Melbourne's East African community recruited via community leaders and snowball sampling. Fifty‐five per cent of the sample reported khat use and the remainder reported only having experience of other people's use of the drug.

Results. Participants who did not report chewing khat were mainly concerned with the negative social impacts of its use, such as the extended time men spent away from their families while consuming the drug. These participants (mainly women) expressed their hope that khat would be prohibited in Victoria. Participants who reported the use of khat (mainly men) reported that any social problems existed independently of khat consumption.

Discussion and Conclusions. This study found only limited evidence that khat use has been impacting directly on people's health and well‐being. Any moves to prohibit khat use may further marginalise already vulnerable groups of people.[Feigin A, Higgs P, Hellard M, Dietze P. The impact of khat use on East African communities in Melbourne: A preliminary investigation. Drug Alcohol Rev 2012;31:288–293]
An Exercise to Introduce Power
Authors: Seier Edith , Liu Yali
Published: April 2011

In introductory statistics courses, the concept of power is usually presented in the context of testing hypotheses about the population mean. We instead propose an exercise that uses a binomial probability table to introduce the idea of power in the context of testing a population proportion.
Sensitivity analysis in statistics teaching
Authors: Zhang Lingyun , Govindaraju Kondaswamy
Published: April 2011

The need to encourage what if questions for statistical thinking in a classroom environment is stressed in this article.
No evidence of APP point mutation and locus duplication in individuals with cerebral amyloid angiopathy
Authors: Domingues‐Montanari S. , Parés M. , Hernández‐Guillamon M. , Fernández‐Cadenas I. , Mendioroz M. , Ortega G. , Boada M. , Masjuan J. , Huertas N. , Álvarez‐Sabín J. , Delgado P. , Montaner J. ,   for the Stroke Project of the Cerebrovascular Diseases Study Group, Spanish Society of Neurology
Published: April 2011

Background:  Cerebral amyloid angiopathy (CAA) is a well‐established cause of lobar intracerebral hemorrhage (ICH). Familial forms of CAA are because of mutations in the gene encoding the beta‐amyloid precursor protein (APP) and duplications of this gene can cause early‐onset Alzheimer’s disease associated with CAA. However, the contribution of APP genetic variants in the development of sporadic CAA remains unknown.

Methods:  The presence of genetic variants in the APP was examined in 78 patients with CAA‐related ICH by sequencing exons 16 and 17 coding the β‐amyloid protein and analyzing the presence of possible duplications of APP by microsatellite analysis and quantitative PCR.

Results:  We did not identify any pathogenic mutation or chromosomal duplication of APP.

Conclusions:  Our results suggest that APP genetic variants, point mutations and locus duplication, are not a common cause of CAA‐related ICH in the Spanish population.
NON‐DESTRUCTIVE CHEMICAL ANALYSIS OF OLD SOUTH ARABIAN COINS, FOURTH CENTURY BCE TO THIRD CENTURY CE
Authors: KIRFEL A. , KOCKELMANN W. , YULE P.
Published: April 2011

Studies on Old South Arabian (OSA) coinage are rare and state‐of‐the‐art materials analysis for them lags far behind that of ancient Greece and Rome. Understandably, numismatists responsible for preserving their collections discourage destructive analyses. We have selected coins of the aesthetically and technically developed Himyarite Royal Raydan series (early first to late second centuryce), so‐called Old and New Style Athenian Imitations, among others to provide a wide spectrum of information on OSA coinage. We used non‐destructive neutron diffraction to ascertain the metal compositions and corrosion products. Density determinations using gas‐pycnometry support these experiments. The results provide detailed information with regard to a small, apparently homogeneous, selection of 10 Himyarite period specimens and first insights into the actual and the original metal compositions of about 90 coins of the three main OSA numismatic groups. The analytical results make clear which OSA coins originally were struck and which ones were cast. The analyses provide not only detailed information concerning the manufacture of the selected representative coins, but also suffice to cast a shadow on the reliability of commonplace macro‐optical classification, which proves often to be inaccurate.
FIELD AND LABORATORY MULTI‐TECHNIQUE ANALYSIS OF PIGMENTS AND ORGANIC PAINTING MEDIA FROM AN EGYPTIAN COFFIN (26TH DYNASTY)
Authors: BONIZZONI L. , BRUNI S. , GUGLIELMI V. , MILAZZO M. , NERI O.
Published: April 2011

This paper describes the physico‐chemical analyses performed on an Egyptian wood coffin on the occasion of its restoration in the hall of the National Archaeological Museum of Parma (Italy), with the aim of investigating the pigments and organic materials originally used. Pigment determination was performed both in situ by a portable energy‐dispersive X‐ray fluorescence (EDXRF) spectrometer and in the laboratory using a micro‐Fourier‐transform‐infrared (micro‐FTIR) and a Fourier‐transform (FT) Raman spectrometer. The identification of organic materials was performed through gas chromatography – mass spectrometry (GC–MS) and micro‐FTIR analysis. Amongst the pigments, special attention was paid to the green, which appeared to be severely degraded and was examined using powder X‐ray diffraction (XRD) and scanning electron microscopy – energy‐dispersive X‐ray (SEM–EDX) in addition to the above‐cited techniques. Other materials used in the polychromatic decorations are Egyptian blue, cinnabar and possibly orpiment, while calcium carbonate was used for the ground layer. The organic materials were identified as beeswax, mastic and gum arabic, sometimes as mixtures.