bluuebunny/crossref_metadata_2025 huggingface dataset:
Intrinsic cortical dynamics dominate population responses to natural images across human visual cortex
Authors: Henriksson Linda , Khaligh-Razavi Seyed-Mahdi , Kay Kendrick , Kriegeskorte Nikolaus
Published: September 2014

Intrinsic cortical dynamics are thought to underlie trial-to-trial variability of visually evoked responses in animal models. Understanding their function in the context of sensory processing and representation is a major current challenge. Here we report that intrinsic cortical dynamics strongly affect the representational geometry of a brain region, as reflected in response-pattern dissimilarities, and exaggerate the similarity of representations between brain regions. We characterized the representations in several human visual areas by representational dissimilarity matrices (RDMs) constructed from fMRI response-patterns for natural image stimuli. The RDMs of different visual areas were highly similar when the response-patterns were estimated on the basis of the same trials (sharing intrinsic cortical dynamics), and quite distinct when patterns were estimated on the basis of separate trials (sharing only the stimulus-driven component). We show that the greater similarity of the representational geometries can be explained by the coherent fluctuations of regional-mean activation within visual cortex, reflecting intrinsic dynamics. Using separate trials to study stimulus-driven representations revealed clearer distinctions between the representational geometries: a Gabor wavelet pyramid model explained representational geometry in visual areas V1–3 and a categorical animate– inanimate model in the object-responsive lateral occipital cortex.
Behavioral individuality reveals genetic control of phenotypic variability
Authors: Ayroles Julien F , Buchanan Sean M , Jenney Chelsea , Skutt-Kakaria Kyobi , Grenier Jennifer , Clark Andrew G , Hartl Daniel L , de Bivort Benjamin L
Published: September 2014

Variability is ubiquitous in nature and a fundamental feature of complex systems. Few studies, however, have investigated variance itself as a trait under genetic control. By focusing primarily on trait means and ignoring the effect of alternative alleles on trait variability, we may be missing an important axis of genetic variation contributing to phenotypic differences among individuals. To study genetic effects on individual-to-individual phenotypic variability (or intragenotypic variability), we used a panel of Drosophila inbred lines and focused on locomotor handedness, in an assay optimized to measure variability. We discovered that some lines had consistently high levels of intragenotypic variability among individuals while others had low levels. We demonstrate that the degree of variability is itself heritable. Using a genome-wide association study (GWAS) for the degree of intragenotypic variability as the phenotype across lines, we identified several genes expressed in the brain that affect variability in handedness without affecting the mean. One of these genes, Ten-a, implicated a neuropil in the central complex of the fly brain as influencing the magnitude of behavioral variability, a brain region involved in sensory integration and locomotor coordination. We have validated these results using genetic deficiencies, null alleles, and inducible RNAi transgenes. This study reveals the constellation of phenotypes that can arise from a single genotype and it shows that different genetic backgrounds differ dramatically in their propensity for phenotypic variability. Because traditional mean-focused GWASs ignore the contribution of variability to overall phenotypic variation, current methods may miss important links between genotype and phenotype.
A formal perturbation equation between genotype and phenotype determines the Evolutionary Action of protein-coding variations on fitness
Authors: Katsonis Panagiotis , Lichtarge Olivier
Published: September 2014

The relationship between genotype mutations and phenotype variations determines health in the short term and evolution over the long term, and it hinges on the action of mutations on fitness. A fundamental difficulty in determining this action, however, is that it depends on the unique context of each mutation, which is complex and often cryptic. As a result, the effect of most genome variations on molecular function and overall fitness remains unknown and stands apart from population genetics theories linking fitness effect to polymorphism frequency. Here, we hypothesize that evolution is a continuous and differentiable physical process coupling genotype to phenotype. This leads to a formal equation for the action of coding mutations on fitness that can be interpreted as a product of the evolutionary importance of the mutated site with the difference in amino acid similarity. Approximations for these terms are readily computable from phylogenetic sequence analysis, and we show mutational, clinical, and population genetic evidence that this action equation predicts the effect of point mutations in vivo and in vitro in diverse proteins, correlates disease-causing gene mutations with morbidity, and determines the frequency of human coding polymorphisms, respectively. Thus, elementary calculus and phylogenetics can be integrated into a perturbation analysis of the evolutionary relationship between genotype and phenotype that quantitatively links point mutations to function and fitness and that opens a new analytic framework for equations of biology. In practice, this work explicitly bridges molecular evolution with population genetics with applications from protein redesign to the clinical assessment of human genetic variations.
Heterogeneous polymerase fidelity and mismatch repair bias genome variation and composition
Authors: Lujan Scott A. , Clausen Anders R. , Clark Alan B. , MacAlpine Heather K. , MacAlpine David M. , Malc Ewa P. , Mieczkowski Piotr A. , Burkholder Adam B. , Fargo David C. , Gordenin Dmitry A. , Kunkel Thomas A.
Published: September 2014

Mutational heterogeneity must be taken into account when reconstructing evolutionary histories, calibrating molecular clocks, and predicting links between genes and disease. Selective pressures and various DNA transactions have been invoked to explain the heterogeneous distribution of genetic variation between species, within populations, and in tissue-specific tumors. To examine relationships between such heterogeneity and variations in leading- and lagging-strand replication fidelity and mismatch repair, we accumulated 40,000 spontaneous mutations in eight diploid yeast strains in the absence of selective pressure. We found that replicase error rates vary by fork direction, coding state, nucleosome proximity, and sequence context. Further, error rates and DNA mismatch repair efficiency both vary by mismatch type, responsible polymerase, replication time, and replication origin proximity. Mutation patterns implicate replication infidelity as one driver of variation in somatic and germline evolution, suggest mechanisms of mutual modulation of genome stability and composition, and predict future observations in specific cancers.
Targeted Mutagenesis of the Tomato PROCERA Gene Using Transcription Activator-Like Effector Nucleases
Authors: Lor Vai S. , Starker Colby G. , Voytas Daniel F. , Weiss David , Olszewski Neil E.
Published: September 2014

Transcription activator-like effector nucleases successfully generate a heritable tomato mutant.
Structural Studies of Cinnamoyl-CoA Reductase and Cinnamyl-Alcohol Dehydrogenase, Key Enzymes of Monolignol Biosynthesis
Authors: Pan Haiyun , Zhou Rui , Louie Gordon V. , Mühlemann Joëlle K. , Bomati Erin K. , Bowman Marianne E. , Dudareva Natalia , Dixon Richard A. , Noel Joseph P. , Wang Xiaoqiang
Published: September 2014

The enzymes cinnamoyl-CoA reductase (CCR) and cinnamyl alcohol dehydrogenase (CAD) catalyze the two key reduction reactions in the conversion of cinnamic acid derivatives into monolignol building blocks for lignin polymers in plant cell walls. Here, we describe detailed functional and structural analyses of CCRs from Medicago truncatula and Petunia hybrida and of an atypical CAD (CAD2) from M. truncatula. These enzymes are closely related members of the short-chain dehydrogenase/reductase (SDR) superfamily. Our structural studies support a reaction mechanism involving a canonical SDR catalytic triad in both CCR and CAD2 and an important role for an auxiliary cysteine unique to CCR. Site-directed mutants of CAD2 (Phe226Ala and Tyr136Phe) that enlarge the phenolic binding site result in a 4- to 10-fold increase in activity with sinapaldehyde, which in comparison to the smaller coumaraldehyde and coniferaldehyde substrates is disfavored by wild-type CAD2. This finding demonstrates the potential exploitation of rationally engineered forms of CCR and CAD2 for the targeted modification of monolignol composition in transgenic plants. Thermal denaturation measurements and structural comparisons of various liganded and unliganded forms of CCR and CAD2 highlight substantial conformational flexibility of these SDR enzymes, which plays an important role in the establishment of catalytically productive complexes of the enzymes with their NADPH and phenolic substrates.
ROP3 GTPase Contributes to Polar Auxin Transport and Auxin Responses and Is Important for Embryogenesis and Seedling Growth inArabidopsis
Authors: Huang Jia-bao , Liu Huili , Chen Min , Li Xiaojuan , Wang Mingyan , Yang Yali , Wang Chunling , Huang Jiaqing , Liu Guolan , Liu Yuting , Xu Jian , Cheung Alice Y. , Tao Li-zhen
Published: September 2014

ROP GTPases are crucial for the establishment of cell polarity and for controlling responses to hormones and environmental signals in plants. In this work, we show that ROP3 plays important roles in embryo development and auxin-dependent plant growth. Loss-of-function and dominant-negative (DN) mutations in ROP3 induced a spectrum of similar defects starting with altered cell division patterning during early embryogenesis to postembryonic auxin-regulated growth and developmental responses. These resulted in distorted embryo development, defective organ formation, retarded root gravitropism, and reduced auxin-dependent hypocotyl elongation. Our results showed that the expression of AUXIN RESPONSE FACTOR5/MONOPTEROS and root master regulators PLETHORA1 (PLT1) and PLT2 was reduced in DN-rop3 mutant embryos, accounting for some of the observed patterning defects. ROP3 mutations also altered polar localization of auxin efflux proteins (PINs) at the plasma membrane (PM), thus disrupting auxin maxima in the root. Notably, ROP3 is induced by auxin and prominently detected in root stele cells, an expression pattern similar to those of several stele-enriched PINs. Our results demonstrate that ROP3 is important for maintaining the polarity of PIN proteins at the PM, which in turn ensures polar auxin transport and distribution, thereby controlling plant patterning and auxin-regulated responses.
Arabidopsis thaliana RNase H2 Deficiency Counteracts the Needs for the WEE1 Checkpoint Kinase but Triggers Genome Instability
Authors: Kalhorzadeh Pooneh , Hu Zhubing , Cools Toon , Amiard Simon , Willing Eva-Maria , De Winne Nancy , Gevaert Kris , De Jaeger Geert , Schneeberger Korbinian , White Charles I. , De Veylder Lieven
Published: September 2014

The WEE1 kinase is an essential cell cycle checkpoint regulator in Arabidopsis thaliana plants experiencing replication defects. Whereas under non-stress conditions WEE1-deficient plants develop normally, they fail to adapt to replication inhibitory conditions, resulting in the accumulation of DNA damage and loss of cell division competence. We identified mutant alleles of the genes encoding subunits of the ribonuclease H2 (RNase H2) complex, known for its role in removing ribonucleotides from DNA-RNA duplexes, as suppressor mutants of WEE1 knockout plants. RNase H2 deficiency triggered an increase in homologous recombination (HR), correlated with the accumulation of γ-H2AX foci. However, as HR negatively impacts the growth of WEE1-deficient plants under replication stress, it cannot account for the rescue of the replication defects of the WEE1 knockout plants. Rather, the observed increase in ribonucleotide incorporation in DNA indicates that the substitution of deoxynucleotide with ribonucleotide abolishes the need for WEE1 under replication stress. Strikingly, increased ribonucleotide incorporation in DNA correlated with the occurrence of small base pair deletions, identifying the RNase H2 complex as an important suppressor of genome instability.
Adjustment of Host Cells for Accommodation of Symbiotic Bacteria: Vacuole Defunctionalization, HOPS Suppression, and TIP1g Retargeting in Medicago
Authors: Gavrin Aleksandr , Kaiser Brent N. , Geiger Dietmar , Tyerman Stephen D. , Wen Zhengyu , Bisseling Ton , Fedorova Elena E.
Published: September 2014

In legume–rhizobia symbioses, the bacteria in infected cells are enclosed in a plant membrane, forming organelle-like compartments called symbiosomes. Symbiosomes remain as individual units and avoid fusion with lytic vacuoles of host cells. We observed changes in the vacuole volume of infected cells and thus hypothesized that microsymbionts may cause modifications in vacuole formation or function. To examine this, we quantified the volumes and surface areas of plant cells, vacuoles, and symbiosomes in root nodules of Medicago truncatula and analyzed the expression and localization of VPS11 and VPS39, members of the HOPS vacuole-tethering complex. During the maturation of symbiosomes to become N2-fixing organelles, a developmental switch occurs and changes in vacuole features are induced. For example, we found that expression of VPS11 and VPS39 in infected cells is suppressed and host cell vacuoles contract, permitting the expansion of symbiosomes. Trafficking of tonoplast-targeted proteins in infected symbiotic cells is also altered, as shown by retargeting of the aquaporin TIP1g from the tonoplast membrane to the symbiosome membrane. This retargeting appears to be essential for the maturation of symbiosomes. We propose that these alterations in the function of the vacuole are key events in the adaptation of the plant cell to host intracellular symbiotic bacteria.
ABCG Transporters Are Required for Suberin and Pollen Wall Extracellular Barriers inArabidopsis
Authors: Yadav Vandana , Molina Isabel , Ranathunge Kosala , Castillo Indira Queralta , Rothstein Steven J. , Reed Jason W.
Published: September 2014

Effective regulation of water balance in plants requires localized extracellular barriers that control water and solute movement. We describe a clade of five Arabidopsis thaliana ABCG half-transporters that are required for synthesis of an effective suberin barrier in roots and seed coats (ABCG2, ABCG6, and ABCG20) and for synthesis of an intact pollen wall (ABCG1 and ABCG16). Seed coats of abcg2 abcg6 abcg20 triple mutant plants had increased permeability to tetrazolium red and decreased suberin content. The root system of triple mutant plants was more permeable to water and salts in a zone complementary to that affected by the Casparian strip. Suberin of mutant roots and seed coats had distorted lamellar structure and reduced proportions of aliphatic components. Root wax from the mutant was deficient in alkylhydroxycinnamate esters. These mutant plants also had few lateral roots and precocious secondary growth in primary roots. abcg1 abcg16 double mutants defective in the other two members of the clade had pollen with defects in the nexine layer of the tapetum-derived exine pollen wall and in the pollen-derived intine layer. Mutant pollen collapsed at the time of anther desiccation. These mutants reveal transport requirements for barrier synthesis as well as physiological and developmental consequences of barrier deficiency.
Sterol Side Chain Reductase 2 Is a Key Enzyme in the Biosynthesis of Cholesterol, the Common Precursor of Toxic Steroidal Glycoalkaloids in Potato
Authors: Sawai Satoru , Ohyama Kiyoshi , Yasumoto Shuhei , Seki Hikaru , Sakuma Tetsushi , Yamamoto Takashi , Takebayashi Yumiko , Kojima Mikiko , Sakakibara Hitoshi , Aoki Toshio , Muranaka Toshiya , Saito Kazuki , Umemoto Naoyuki
Published: September 2014

Potatoes (Solanum tuberosum) contain α-solanine and α-chaconine, two well-known toxic steroidal glycoalkaloids (SGAs). Sprouts and green tubers accumulate especially high levels of SGAs. Although SGAs were proposed to be biosynthesized from cholesterol, the biosynthetic pathway for plant cholesterol is poorly understood. Here, we identify sterol side chain reductase 2 (SSR2) from potato as a key enzyme in the biosynthesis of cholesterol and related SGAs. Using in vitro enzyme activity assays, we determined that potato SSR2 (St SSR2) reduces desmosterol and cycloartenol to cholesterol and cycloartanol, respectively. These reduction steps are branch points in the biosynthetic pathways between C-24 alkylsterols and cholesterol in potato. Similar enzymatic results were also obtained from tomato SSR2. St SSR2-silenced potatoes or St SSR2-disrupted potato generated by targeted genome editing had significantly lower levels of cholesterol and SGAs without affecting plant growth. Our results suggest that St SSR2 is a promising target gene for breeding potatoes with low SGA levels.
Hypomethylated Pollen Bypasses the Interploidy Hybridization Barrier inArabidopsis
Authors: Schatlowski Nicole , Wolff Philip , Santos-González Juan , Schoft Vera , Siretskiy Alexey , Scott Rod , Tamaru Hisashi , Köhler Claudia
Published: September 2014

Plants of different ploidy levels are separated by a strong postzygotic hybridization barrier that is established in the endosperm. Deregulated parent-of-origin specific genes cause the response to interploidy hybridizations, revealing an epigenetic basis of this phenomenon. In this study, we present evidence that paternal hypomethylation can bypass the interploidy hybridization barrier by alleviating the requirement for the Polycomb Repressive Complex 2 (PRC2) in the endosperm. PRC2 epigenetically regulates gene expression by applying methylation marks on histone H3. Bypass of the barrier is mediated by suppressed expression of imprinted genes. We show that the hypomethylated pollen genome causes de novo CHG methylation directed to FIS-PRC2 target genes, suggesting that different epigenetic modifications can functionally substitute for each other. Our work presents a method for the generation of viable triploids, providing an impressive example of the potential of epigenome manipulations for plant breeding.
The Impact of Massachusetts Health Care Reform on Access, Quality, and Costs of Care for the Already‐Insured
Authors: Joynt Karen E. , Chan David C. , Zheng Jie , Orav E. John , Jha Ashish K.
Published: September 2014

Objective

To assess the impact of Massachusetts Health Reform (MHR) on access, quality, and costs of outpatient care for the already‐insured.

Data Sources/Study Setting

Medicare data from before (2006) and after (2009) MHR implementation.

Study Design

We performed a retrospective difference‐in‐differences analysis of quantity of outpatient visits, proportion of outpatient quality metrics met, and costs of care for Medicare patients with ≥1 chronic disease in 2006 versus 2009. We used the remaining states in New England as controls.

Data Collection/Extraction Methods

We used existing Medicare claims data provided by the Centers for Medicare and Medicaid Services.

Principal Findings

MHR was not associated with a decrease in outpatient visits per year compared to controls (9.4 prereform to 9.6 postreform in MA vs. 9.4–9.5 in controls, p = .32). Quality of care in MA improved more than controls for hemoglobin A1c monitoring, mammography, and influenza vaccination, and similarly to controls for diabetic eye examination, colon cancer screening, and pneumococcal vaccination. Average costs for patients in Massachusetts increased from $9,389 to $10,668, versus $8,375 to $9,114 in control states (p < .001).

Conclusions

MHR was not associated with worsening in access or quality of outpatient care for the already‐insured, and it had modest effects on costs. This has implications for other states expanding insurance coverage under the Affordable Care Act.
Masculinity, Testosterone, and Financial Misreporting
Authors: JIA YUPING , LENT LAURENCE VAN , ZENG YACHANG
Published: September 2014

We examine the relation between a measure of male CEOs’ facial masculinity and financial misreporting. Facial masculinity is associated with a complex of masculine behaviors (including aggression, egocentrism, riskseeking, and maintenance of social status) in males. One possible mechanism for this relation is that the hormone testosterone influences both behavior and the development of the face shape. We document a positive association between CEO facial masculinity and various misreporting proxies in a broad sample of S&P1500 firms during 1996–2010. We complement this evidence by documenting that a CEO's facial masculinity predicts his firm's likelihood of being subject to an SEC enforcement action. We also show that an executive's facial masculinity is associated with the likelihood of the SEC naming him as a perpetrator. We find that facial masculinity is not a measure of overconfidence. Finally, we demonstrate that facial masculinity also predicts the incidence of insider trading and option backdating.
Biocontrol and plant growth‐promoting activity of rhizobacteria from Chinese fields with contaminated soils
Authors: Wang Xuefei , Mavrodi Dmitri V. , Ke Linfeng , Mavrodi Olga V. , Yang Mingming , Thomashow Linda S. , Zheng Na , Weller David M. , Zhang Jibin
Published: September 2014

The aim of this study was to inventory the types of plant growth‐promoting rhizobacteria (PGPR) present in the rhizosphere of plants grown in soils contaminated with heavy metals, recalcitrant organics, petroleum sewage or salinity in China. We screened 1223 isolates for antifungal activity and about 24% inhibited Rhizoctonia solani or Sclerotinia sclerotiorum. Twenty‐four strains inhibitory to R. solani, Gaeumannomyces graminis var. tritici and/or S. sclerotiorum and representing the dominant morphotypes were assayed for PGPR activity. Seven strains contained phlD, prnD, pltC or phzF genes and produced the antibiotics 2,4‐diacetylphloroglucinol, pyrrolnitrin, pyoluteorin and phenazines respectively. Six strains contained acdS, which encodes 1‐aminocyclopropane‐1‐carboxylic acid deaminase. Phylogenetic analysis of 16S rDNA and phlD, phzF and acdS genes demonstrated that some strains identified as Pseudomonas were similar to model PGPR strains Pseudomonas protegens Pf‐5, Pseudomonas chlororaphis subsp. aureofaciens 30–84 and P. brassicacearum Q8r1‐96. Pseudomonas protegens‐ and P. chlororaphis‐like strains had the greatest biocontrol activity against Rhizoctonia root rot and take‐all of wheat. Pseudomonas protegens and P. brassicacearum‐like strains showed the greatest promotion of canola growth. Our results indicate that strains from contaminated soils are similar to well‐described PGPR found in agricultural soils worldwide.
Genomic exploration and molecular marker development in a large and complex conifer genome using RADseq and mRNAseq
Authors: Karam M.‐J. , Lefèvre F. , Dagher‐Kharrat M. Bou , Pinosio S. , Vendramin G.G.
Published: September 2014

We combined restriction site associated DNA sequencing (RADseq) using a hypomethylation‐sensitive enzyme and messenger RNA sequencing (mRNAseq) to develop molecular markers for the 16 gigabase genome of Cedrus atlantica, a conifer tree species. With each method, Illumina® reads from one individual were used to generate de novo assemblies. SNPs from the RADseq data set were detected in a panel of one single individual and three pools of three individuals each. We developed a flexible script to estimate the ascertainment bias in SNP detection considering the pooling and sampling effects on the probability of not detecting an existing polymorphism. Gene Ontology (GO) and transposable element (TE) search analyses were applied to both data sets. The RADseq and the mRNAseq assemblies represented 0.1% and 0.6% of the genome, respectively. Genome complexity reduction resulted in 17% of the RADseq contigs potentially coding for proteins. This rate was doubled in the mRNAseq data set, suggesting that RADseq also explores noncoding low‐repeat regions. The two methods gave very similar GO‐slim profiles. As expected, the two assemblies were poor in TE‐like sequences (<4% of contigs length). We identified 17,348 single nucleotide polymorphisms (SNPs) in the RADseq data set and 5,714 simple sequence repeats (SSRs) in the transcriptome. A subset of 282 SNPs was validated using the Fluidigm genotyping technology, giving a conversion rate of 50.4%, falling within the expected range for conifers. Increasing sample size had the greatest effect for ascertainment bias reduction. These results validated the utility of the RADseq approach for highly complex genomes such as conifers.
A comparison of single nucleotide polymorphism and microsatellite markers for analysis of parentage and kinship in a cooperatively breeding bird
Authors: Weinman Lucia R. , Solomon Joseph W. , Rubenstein Dustin R.
Published: September 2014

The development of genetic markers has revolutionized molecular studies within and among populations. Although poly‐allelic microsatellites are the most commonly used genetic marker for within‐population studies of free‐living animals, biallelic single nucleotide polymorphisms, or SNPs, have also emerged as a viable option for use in nonmodel systems. We describe a robust method of SNP discovery from the transcriptome of a nonmodel organism that resulted in more than 99% of the markers working successfully during genotyping. We then compare the use of 102 novel SNPs with 15 previously developed microsatellites for studies of parentage and kinship in cooperatively breeding superb starlings (Lamprotornis superbus) that live in highly kin‐structured groups. For 95% of the offspring surveyed, SNPs and microsatellites identified the same genetic father, but only when behavioural information about the likely parents at a nest was included to aid in assignment. Moreover, when such behavioural information was available, the number of SNPs necessary for successful parentage assignment was reduced by half. However, in a few cases where candidate fathers were highly related, SNPs did a better job at assigning fathers than microsatellites. Despite high variation between individual pairwise relatedness values, microsatellites and SNPs performed equally well in kinship analyses. This study is the first to compare SNPs and microsatellites for analyses of parentage and relatedness in a species that lives in groups with a complex social and kin structure. It should also prove informative for those interested in developing SNP loci from transcriptome data when published genomes are unavailable.
Simultaneous detection of major blackleg and soft rot bacterial pathogens in potato by multiplex polymerase chain reaction
Authors: Potrykus M. , Sledz W. , Golanowska M. , Slawiak M. , Binek A. , Motyka A. , Zoledowska S. , Czajkowski R. , Lojkowska E.
Published: September 2014

A multiplex polymerase chain reaction (PCR) assay for simultaneous, fast and reliable detection of the main soft rot and blackleg potato pathogens in Europe has been developed. It utilises three pairs of primers and enables detection of three groups of pectinolytic bacteria frequently found in potato, namely: Pectobacterium atrosepticum, Pectobacterium carotovorum subsp. carotovorum together with Pectobacterium wasabiae and Dickeya spp. in a multiplex PCR assay. In studies with axenic cultures of bacteria, the multiplex assay was specific as it gave positive results only with strains of the target species and negative results with 18 non‐target species of bacteria that can possibly coexist with pectinolytic bacteria in a potato ecosystem. The developed assay could detect as little as 0.01 ng µL–1 of Dickeya sp. genomic DNA, and down to 0.1 ng µL–1 of P. atrosepticum and P. carotovorum subsp. carotovorum genomic DNA in vitro. In the presence of competitor genomic DNA, isolated from Pseudomonas fluorescens cells, the sensitivity of the multiplex PCR decreased tenfold for P. atrosepticum and Dickeya sp., while no change was observed for P. carotovorum subsp. carotovorum and P. wasabiae. In spiked potato haulm and tuber samples, the threshold level for target bacteria was 101 cfu mL–1 plant extract (102 cfu g–1 plant tissue), 102 cfu mL–1 plant extract (103 cfu g–1 plant tissue), 103 cfu mL–1 plant extract (104 cfu g–1 plant tissue), for Dickeya spp., P. atrosepticum and P. carotovorum subsp. carotovorum/P. wasabiae, respectively. Most of all, this assay allowed reliable detection and identification of soft rot and blackleg pathogens in naturally infected symptomatic and asymptomatic potato stem and progeny tuber samples collected from potato fields all over Poland.
ET‐1 increases reactive oxygen species following hypoxia and high‐salt diet in the mouse glomerulus
Authors: Heimlich J. B. , Speed J. S. , Bloom C. J. , O'Connor P. M. , Pollock J. S. , Pollock D. M.
Published: September 2014

Aim

This study was designed to determine whether ET‐1 derived from endothelial cells contributes to oxidative stress in the glomerulus of mice subjected to a high‐salt diet and/or hypoxia.

Methods

C57BL6/J control mice or vascular endothelial cell ET‐1 knockout (VEET KO) mice were subjected to 3‐h exposure to hypoxia (8% O2) and/or 2 weeks of high‐salt diet (4% NaCl) prior to metabolic cage assessment of renal function and isolation of glomeruli for the determination of reactive oxygen species (ROS).

Results

In control mice, hypoxia significantly increased urinary protein excretion during the initial 24 h, but only in animals on a high‐salt diet. Hypoxia increased glomerular ET‐1 mRNA expression in control, but not in vascular endothelial cell ET‐1 knockout (VEET KO) mice. Under normoxic conditions, mice on a high‐salt diet had approx. 150% higher glomerular ET‐1 mRNA expression compared with a normal‐salt diet (P < 0.05). High‐salt diet administration significantly increased glomerular ROS production in flox control, but not in glomeruli isolated from VEET KO mice. In C57BL6/J mice, the ETA receptor‐selective antagonist, ABT‐627, significantly attenuated the increase in glomerular ROS production produced by high‐salt diet. In addition, chronic infusion of C57BL6/J mice with a subpressor dose of ET‐1 (osmotic pumps) significantly increased the levels of glomerular ROS that were prevented by ETA antagonist treatment.

Conclusion

These data suggest that both hypoxia and a high‐salt diet increase glomerular ROS production via endothelial‐derived ET‐1‐ETA receptor activation and provide a potential mechanism for ET‐1‐induced nephropathy.
Anti‐transforming growth factor β‐induced protein antibody ameliorates vascular barrier dysfunction and improves survival in sepsis
Authors: Bae J.‐S. , Lee W. , Son H.‐N. , Lee Y.‐M. , Kim I.‐S.
Published: September 2014

Aim

Sepsis is a systemic inflammatory response syndrome resulting from a microbial infection. Transforming growth factor β‐induced protein (TGFBIp) is an extracellular matrix protein expressed by human endothelial cells and platelets that induces sepsis through interaction with integrin αvβ5. The aim of this study was to investigate the role of TGFBIp in vascular permeability and the underlying mechanisms using TGFBIp‐neutralizing antibody.

Methods

Mice were subjected to caecal ligation and puncture (CLP) with or without neutralizing anti‐TGFBIp antibody (300 μg kg−1, intravenously). Wild‐type or integrin β5‐null mice received TGFBIp (0.1 mg kg−1, intravenously) or were subjected to CLP. Human umbilical vein endothelial cells were exposed to lipopolysaccharide (100 ng mL−1) with or without neutralizing anti‐TGFBIp antibody (50 μg mL−1).

Results

Administration of neutralizing anti‐TGFBIp antibody in mice attenuated CLP‐induced secretion of TGFBIp, leucocyte migration and vascular permeability and reduced septic mortality. Injected TGFBIp did not enhance vascular barrier permeability or leucocyte migration in β5‐null mice. Finally, neutralizing anti‐TGFBIp antibody inhibited the specific interactions between TGFBIp and its receptor, integrin αvβ5.

Conclusion

Our findings demonstrate that treatment with a TGFBIp‐neutralizing antibody can ameliorate the deleterious effects of sepsis.
Long‐term climate forcings to assess vulnerability in North Africa dry argan woodlands
Authors: Alba‐Sánchez Francisca , López‐Sáez José Antonio , Nieto‐Lugilde Diego , Svenning Jens‐Christian
Published: September 2014

Questions

North African dry woodlands constitute mediterranean climatic ecotone ecosystems of vital importance for human livelihoods and local biodiversity. To improve the basis for managing these key ecosystems, we selected a Tertiary relict woodland (Argania spinosa) in order to clarify the sensitivity to long‐term climate change (the present, the past glacial‐interglacial cycle and under future scenarios). We also discuss the impact of long‐term human land use for the distribution of dry woodlands in North Africa.

Location

North Africa.

Methods

To assess whether the argan woodland is in equilibrium with current climate, we used species distribution modelling (SDM) to estimate its potential range. Then, SDM was used to estimate its potential distribution during the Last Glacial Maximum (LGM; 21,000 BP) and the Middle Holocene (Mid‐Holocene; 6,000 BP). Model predictions for past scenarios were compared with Quaternary palaeorecords to evaluate their accuracy. Finally, we forecasted changes in the potential range to year 2080 to assess its likely future range dynamics.

Results

At the LGM, suitable areas occurred at more southern latitudes, where the Sahara Desert currently lies, while suitable areas in the Mid‐Holocene shifted northwards, occupying areas similar to those of today. The estimated past distributions are consistent with palaeorecords, providing evidence for the important role of Quaternary climate changes in driving dry woodland range dynamics. The current range‐filling constitutes 44% of the potential distribution, probably primarily reflecting anthropic land‐use effects. Future climate change is forecast not to cause latitudinal/altitudinal range shifts, but rather an overall range contraction.

Conclusions

The models reflect the high sensitivity of the dry woodland ecosystem to past climate changes, in agreement with palaeorecords. The estimated climatic sensitivity also predicts severe range contraction during future climate change. Consequently, management strategies for dry woodlands should be developed to facilitate their in situ survival, particularly by reducing the currently intensive human pressure.
Changes of cortical excitability as markers of antidepressant response in bipolar depression: preliminary data obtained by combining transcranial magnetic stimulation (TMS) and electroencephalography (EEG)
Authors: Canali Paola , Sferrazza Papa Giovanna , Casali Adenauer G , Schiena Giandomenico , Fecchio Matteo , Pigorini Andrea , Smeraldi Enrico , Colombo Cristina , Benedetti Francesco
Published: September 2014

Background

It is still unclear which biological changes are needed to recover from a major depressive episode. Current perspectives focus on cortical synaptic neuroplasticity. Measures of cortical responses evoked by transcranial magnetic stimulation (TMS) change with sleep homeostasic pressure in humans and approximate measures of synaptic strength in animal models. Using repeated total sleep deprivation as a model of antidepressant treatment, we aimed to correlate recovery from depression with these measures of cortical excitability.

Methods

We recorded electroencephalographic responses to TMS in the prefrontal cortex of 21 depressed inpatients with bipolar disorder treated with repeated sleep deprivation combined with light therapy. We performed seven TMS/electroencephalography sessions during one week and calculated three measures of cortical excitability.

Results

Cortical excitability progressively increased during the antidepressant treatment and as a function of time awake. Higher values differentiated responders from non‐responders at baseline and during and after treatment on all measures.

Conclusions

Changes in measures of cortical excitability parallel and predict antidepressant response to combined sleep deprivation and light therapy. Data suggest that promoting cortical plasticity in bipolar depression could be a major effect of successful antidepressant treatments, and that patients not responding could suffer a persistent impairment in their neuroplasticity mechanisms.
Examining the relationships between self‐efficacy, task‐relevant attentional control , and task performance: Evidence from event‐related brain potentials
Authors: Themanson Jason R. , Rosen Peter J.
Published: September 2014

Self‐efficacy (SE) is a modifiable psychosocial factor related to individuals’ beliefs in their capabilities to successfully complete courses of action and has been shown to be positively associated with task performance. The authors hypothesized that one means through which SE is related with improved performance is through enhanced task‐relevant attentional control during task execution. To assess this hypothesis, we examined the relationships between SE and behavioural and neural indices of task performance and task‐relevant attentional control for 76 young adults during the completion of a flanker task. Results showed that greater SE was associated with greater response accuracy and P3b amplitude across task conditions, and faster RT under more difficult task conditions. Additionally, P3b amplitude was found to mediate the relationship between SE and task performance in the difficult condition. These findings suggest that greater attentional allocation to task‐relevant processes, including monitoring stimulus‐response relationships and focusing attention on working memory operations, may help explain the association between SE and improved task performance.
Musical ability and non‐native speech‐sound processing are linked through sensitivity to pitch and spectral information
Authors: Kempe Vera , Bublitz Dennis , Brooks Patricia J.
Published: September 2014

Is the observed link between musical ability and non‐native speech‐sound processing due to enhanced sensitivity to acoustic features underlying both musical and linguistic processing? To address this question, native English speakers (N = 118) discriminated Norwegian tonal contrasts and Norwegian vowels. Short tones differing in temporal, pitch, and spectral characteristics were used to measure sensitivity to the various acoustic features implicated in musical and speech processing. Musical ability was measured using Gordon's Advanced Measures of Musical Audiation. Results showed that sensitivity to specific acoustic features played a role in non‐native speech‐sound processing: Controlling for non‐verbal intelligence, prior foreign language‐learning experience, and sex, sensitivity to pitch and spectral information partially mediated the link between musical ability and discrimination of non‐native vowels and lexical tones. The findings suggest that while sensitivity to certain acoustic features partially mediates the relationship between musical ability and non‐native speech‐sound processing, complex tests of musical ability also tap into other shared mechanisms.
Creative methodologies to enhance communication
Authors: Kennedy Lucille , Brewer Gayle
Published: September 2014

Accessible summary

Those who support people with learning disabilities should listen carefully to what they have to say.

Whilst sharing life stories can be a good way to listen to someone, not everyone is able to talk about their story.

Here, four people who have a learning disability share their stories by singing, taking photographs or making a scrap book, and looking for themes in their work.

The four people enjoyed their work and found that sharing it with others was a helpful way to let people know something about their lives, their skills, and what is important to them.

The experiences and opinions of people with learning disabilities are often ignored or devalued. Oral and life history projects allow individuals to communicate their own opinions and experiences. This process can lead to more meaningful interactions between those with learning disabilities and support workers. Whilst the interview techniques often employed by life history projects may not be appropriate for those with limited verbal abilities, alternative methodologies such as photography, drawings, music and poetry may be adopted. The current study demonstrates that a life history approach incorporating creative techniques can provide valuable information about the beliefs, experiences and values of people with learning disabilities. Therefore, creative forms of communication should be encouraged to promote personalised care and greater representation in learning disability research.
Expression of L‐type amino acid transporter 1 (LAT1) as a prognostic and therapeutic indicator in multiple myeloma
Authors: Isoda Atsushi , Kaira Kyoichi , Iwashina Masanori , Oriuchi Noboru , Tominaga Hideyuki , Nagamori Shushi , Kanai Yoshikatsu , Oyama Tetsunari , Asao Takayuki , Matsumoto Morio , Sawamura Morio
Published: September 2014

L‐type amino‐acid transporter 1 (LAT1) plays a key role in cell growth and survival. To determine the prognostic significance of LAT1 in multiple myeloma (MM), we investigated the expression of LAT1 and its functional subunit, 4Fc heavy chain (CD98), on myeloma cells by immunohistochemistry in 100 newly diagnosed MM patients. High expression (moderate or strong staining intensity) of LAT1 and CD98 was detected in 56% and 45% of patients, respectively. The LAT1 expression score was positively correlated with Ki‐67 index (r = 0.631, P < 0.001), and there was a statistically significant difference in Durie–Salmon stage between patients with high and low LAT1 expression (P = 0.03). In 43 patients treated with melphalan and prednisolone, the overall response rate was significantly higher in the high LAT1 expression group (60.0%) than in the low LAT1 expression group (17.6%) (P = 0.03). Multivariate analysis confirmed that high expression of LAT1 was a significant prognostic factor for predicting poor overall survival independently from the International Staging System (both P = 0.01). Here, we show that the overexpression of LAT1 is significantly associated with high proliferation and poor prognosis in newly diagnosed MM patients. Thus, LAT1 may be a promising pathological marker for identifying high‐risk MM.
Tumor budding in colorectal carcinoma assessed by cytokeratin immunostaining and budding areas: Possible involvement of c‐Met
Authors: Satoh Keisuke , Nimura Satoshi , Aoki Mikiko , Hamasaki Makoto , Koga Kaori , Iwasaki Hiroshi , Yamashita Yuichi , Kataoka Hiroaki , Nabeshima Kazuki
Published: September 2014

Tumor budding/sprouting has been shown to be an independent adverse prognostic factor in T1 and T3N0 colorectal carcinomas, however, its assessment could be improved by more accurate identification of budding carcinoma cells and consideration of budding areas. Moreover, tumor budding mechanisms are yet to be defined. In this study, we evaluated the identification of budding tumor cells by either H&E staining alone or H&E with immunohistochemistry and developed a scoring system based on budding grades and areas. We examined whether the budding score correlated with clinicopathologic features and prognosis and the association between tumor budding/sprouting and c‐Met protein expression and phosphorylation and MET gene copy numbers because c‐Met is known to play an important role in colorectal carcinoma tumorigenesis. Cytokeratin immunohistochemistry could identify tumors with shorter disease‐free survival (DFS) from the low‐grade budding group assessed with H&E alone. High budding scores based on budding grade and area were more significantly correlated with DFS than scores obtained using the budding grade alone. In tumors with a high budding score, c‐Met expression and phosphorylation levels and MET gene copy numbers were significantly increased at the invasive front compared with those in superficial tumor portions. This study showed for the first time that high levels of phospho‐c‐Met at the invasive front were significantly associated with a high budding score and shorter DFS. In conclusion, a budding score assessed by budding grades and budding‐positive areas correlates highly with clinicopathologic aggressive features of colorectal carcinoma.
Prognostic value of stromal cell‐derived factor 1 expression in patients with gastric cancer after surgical resection
Authors: Wang Xuefei , Zhang Heng , He Hongyong , Shen Zhenbin , Tang Zhaoqing , Xu Jiejie , Sun Yihong
Published: September 2014

Aberrant chemokine stromal cell‐derived factor 1 (SDF‐1) expression has been shown to be involved in the development and progression of various malignancies. Our present study aims to investigate the clinical and prognostic value of SDF‐1 expression and improve risk stratification in patients with gastric cancer. Peritumoral and intratumoral SDF‐1 levels were assessed in 220 retrospectively enrolled gastric cancer patients, and their relations with clinicopathological features and clinical outcomes were evaluated. A predictive nomogram was created to refine risk stratification for overall survival of gastric cancer patients. Compared with peritumor tissues, tumor tissues showed decreased SDF‐1 expression levels according to TNM stage progression in gastric cancer specimens. Peritumoral SDF‐1 expression correlated positively with tumor invasion depth and lymph node metastasis, whereas intratumoral SDF‐1 expression associated negatively with tumor size, tumor differentiation, tumor invasion depth, lymph node metastasis, and clinical TNM stage. Moreover, both low peritumoral SDF‐1 expression and high intratumoral SDF‐1 expression indicated favorable overall survival, and SDF‐1 risk derived from the peritumoral/intratumoral SDF‐1 expression signature could stratify prognosis of patients with gastric cancer. After backward elimination, SDF‐1 risk was identified as an independent prognostic factor for survival. Finally, a predictive nomogram was generated with identified independent prognosticators to assess patient survival at 3 and 5 years following surgery. Conclusively, SDF‐1 risk, an identified independent prognostic factor, could be developed into a nomogram with tumor invasion depth, lymph node involvement, and distant metastasis to refine predictive accuracy for survival in patients with gastric cancer after surgical resection.