bluuebunny/crossref_metadata_2025 huggingface dataset:
The Effects of Modified Melodic Intonation Therapy on Nonfluent Aphasia: A Pilot Study
Authors: Conklyn Dwyer , Novak Eric , Boissy Adrienne , Bethoux Francois , Chemali Kamal
Published: March 2012

Objective

Positive results have been reported with melodic intonation therapy (MIT) in nonfluent aphasia patients with damage to their left-brain speech processes, using the patient’s intact ability to sing to promote functional language. This pilot study sought to determine the immediate effects of introducing modified melodic intonation therapy (MMIT), a modification of MIT, as an early intervention in stroke patients presenting with Broca’s aphasia.

Method

After a randomized controlled single-blind design, 30 acute stroke survivors with nonfluent aphasia were randomly assigned to receive MIT treatment or no treatment. A pre/post test, based on the responsive and repetition subsections of the Western Aphasia Battery, was developed for this study.

Results

After 1 session, a significant within-subject change was observed for the treatment group’s adjusted total score (
p
= .02), and a significant difference between groups was found for adjusted total score (
p
= .02) favoring the treatment group. The treatment group also showed a significant change in their responsive subsection scores (
p
= .01) when their pre-tests from Visit 1 to Visit 2 were compared, whereas the control group showed no change, suggesting a possible carry-over effect of MIT treatment.

Conclusion

This study provides preliminary data supporting the possible benefits of utilizing MMIT treatment early in the recovery of nonfluent aphasia patients.
Vowel Category Formation in Korean–English Bilingual Children
Authors: Lee Sue Ann S. , Iverson Gregory K.
Published: March 2012

Purpose

A previous investigation (Lee & Iverson, 2012) found that English and Korean stop categories were fully distinguished by Korean–English bilingual children at 10 years of age but not at 5 years of age. The present study examined vowels produced by Korean–English bilingual children of these same ages to determine whether and when bilinguals establish distinct vowel categories across their 2 languages.

Method

Both English and Korean vowels produced by 40 Korean–English bilingual children (5 and 10 years of age) were examined in terms of 1st formant frequency (F1) and 2nd formant frequency (F2), vowel duration, and F1 and F2 formant trajectories.

Results

Formant frequencies of vowels produced by the bilingual children were similar to those of monolingual English and Korean children. The bilinguals distinguished vowel categories across languages using both the assimilation and dissimilation mechanisms as identified by Flege, Schirru, and MacKay (2003).

Conclusions

Vowel categories developed earlier than stops in bilingual children because vowels were typically acquired earlier than consonants. The results of this study suggest that detailed phonetic categories do not form across the board and that bilingual children may invoke multidimensional representations of phonetic categories.
Acoustics of Clear Speech: Effect of Instruction
Authors: Lam Jennifer , Tjaden Kris , Wilding Greg
Published: March 2012

Purpose

This study investigated how different instructions for eliciting clear speech affected selected acoustic measures of speech.

Method

Twelve speakers were audio-recorded reading 18 different sentences from the Assessment of Intelligibility of Dysarthric Speech (Yorkston & Beukelman, 1984). Sentences were produced in habitual, clear, hearing impaired, and overenunciate conditions. A variety of acoustic measures were obtained.

Results

Relative to habitual, the clear, hearing impaired, and overenunciate conditions were associated with different magnitudes of acoustic change for measures of vowel production, speech timing, and vocal intensity. The overenunciate condition tended to yield the greatest magnitude of change in vowel spectral measures and speech timing, followed by the hearing impaired and clear conditions. SPL tended to be the greatest in the hearing impaired condition for half of the speakers studied.

Conclusions

Different instructions for eliciting clear speech yielded acoustic adjustments of varying magnitude. Results have implications for direct comparison of studies using different instructions for eliciting clear speech. Results also have implications for optimizing clear speech training programs.
Prisonhouses
Authors: Steedman Carolyn
Published: March 2012

Those who live in retirement, whose lives have fallen amid the seclusion of schools and other walled-in and guarded dwellings, are liable to be suddenly and for a long while dropped out of the memory of their friends, the denizens of a freer world … there falls a stilly pause, a wordless silence, a long blank of oblivion. Unbroken always is this blank, alike entire and unexplained. The letter, the message once frequent, are cut off, the visit, formerly periodical, ceases to occur; the book, paper, or other token that indicates remembrance, comes no more.

Always there are excellent reasons for these lapses if the hermit but knew them. Though he is stagnant in his cell, his connections without are whorling in the very vortex of life … The hermit – if he be a sensible hermit – will swallow his own thoughts, and lock up his own emotions during these weeks of inward winter… (Charlotte Brontë, Villette, 1979: 348)
Resisting Amnesia:1 Feminism, Painting and Postmodernism
Authors: Lee Rosa
Published: March 2012

If it is mastery itself which is undergoing deconstruction and if the modern tradition of painting is conventionally recuperated as a tradition of masters, then feminist practice has not surprisingly tended towards the exploration and celebration of its difference(s) at the margins of painting … And yet in this very deconstructive exploration, this celebration of difference, feminist practice reinscribes itself within Tradition and as fundamental to postmodernity. (Phillipson, 1985:188)
The Weary Sons of Freud
Authors: Clément Catherine
Published: March 2012

This article brings together two excerpts from the forthcoming book, The Weary Sons of Freud (Verso/New Left Books, 1987) by Catherine Clément, translated from the French by Nicole Ball. It also includes an edited version of the book's Introduction by Ann Rosalind Jones. Feminist Review would like to thank her for her help in editing this piece, and also Verso/New Left Books for permission to reproduce these extracts.
‘The Problem with no Name’: Rereading Friedan's The Feminine Mystique
Authors: Bowlby Rachel
Published: March 2012

On an April morning in 1959, I heard a mother of four, having coffee with four other mothers in a suburban development fifteen miles from New York, say in a tone of quiet desperation, ‘the problem.’ And the others knew, without words, that she was not talking about a problem with her husband, or her children, or her home. Suddenly they realized they all shared the same problem, the problem that has no name. (Friedan, 1963: 15)1
Equal Employment Opportunity Commission v. Sears, Roebuck and Company: A Personal Account
Authors: Kessler-Harris Alice
Published: March 2012

This article was first published in Radical History Review No. 25, 1986. Since then the controversy has escalated dramatically, with articles in the New York Times and Ms magazine and editorials in the Washington Post. Most of the media have used the controversy as a vehicle to attack women's history and women's studies in general. Had I known the direction that this publicity would take I would have written a much stronger piece. Feminist Studies is planning to publish a piece by Ruth Milkman outlining the issues involved in the case, and Signs will publish some of the written testimony in forthcoming issues.
Still Motion? Motion Illusions and Luminance Contrast
Authors: Hamburger Kai
Published: March 2012

The influence of different luminance contrasts and equiluminance on illusory motion in four inducing patterns was studied: Enigma, Rotating Snakes, Pinna, and Rotating-Tilted-Lines. At high luminance contrast the Pinna and the Rotating-Tilted-Lines illusions are significantly stronger than at low luminance contrast, whereas the Enigma and Rotating Snakes illusions are stronger at low luminance contrast. At equiluminance along the L–M axis the strength of all illusions is greatly reduced. Data suggest that luminance contrast constitutes one important factor for their occurrence.
Plunging into the Pool of Death: Imagining a Dangerous Outcome Influences Distance Perception
Authors: Stefanucci Jeanine K , Gagnon Kyle T , Tompkins Christopher L , Bullock Kendall E
Published: March 2012

We examined whether manipulating the imagined consequences of falling would influence the perception of height, distance, and size. In experiment 1, height and size perception were measured when participants stood at a short height (0.89 m) or a medium height (1.91 m) above either an empty pool or a pool filled with a bed of nails. Participants who viewed the bed of nails and imagined falling into it estimated both the height as taller and the size of the bed of nails as larger than participants who imagined falling into an empty pool. In a second experiment, participants overestimated the horizontal ground distance to and across the bed of nails after being told to imagine jumping over it. Overall, these experiments suggest that costs associated with imagined actions can influence the perception of both vertical and horizontal extents that are not inherently dangerous.
A modelling analysis to identify plant traits for enhanced water-use efficiency of pasture
Authors: White T. A. , Snow V. O.
Published: March 2012

As pressure on water resources increases, pasture species that express traits for improved water-use efficiency (WUE) while maintaining desirable agronomic and production characteristics are needed. The objective of this study was to use a biophysical modelling analysis to test the sensitivity of key pasture plant functional traits on WUE. Biomass production and water use of monocultures of perennial ryegrass (Lolium perenne L.) with varying plant traits were determined under a range of soil, climate, and irrigation conditions. Five plant traits (temperature sensitivity, light extinction, root depth, root partitioning, and sensitivity to water stress) were investigated. Parameters related to root systems had the greatest impact across all environments on harvestable dry matter and WUE. In particular, root depth and root partitioning showed potential for improving both harvestable yield and WUE. These traits merit further attention under more realistic soil conditions, simultaneously taking into consideration other desirable traits such as nutrient capture and agronomic suitability for grazed systems.
Seed production, mass, germinability, and subsequent seedling growth responses to parental warming environment in Leymus chinensis
Authors: Gao Song , Wang Junfeng , Zhang Zhijing , Dong Gang , Guo Jixun
Published: March 2012

Understanding how the seed yield and seed quality respond to global warming is crucial for understanding how new grassland establishment responds to global change. This study evaluated Leymus chinensis, a dominant perennial grass widely distributed in the eastern regions of the Eurasian grassland zone, as a model to investigate the effect of increasing ambient temperature on seed production, seed mass, germinability, and subsequent seedling growth. As the temperature rose, there were significant reductions in the number of flowering plants and in seed number per square metre but significant increase in the number of florets and the number of seeds per plant. Increasing temperature decreased the proportion of light weight seeds, increased the proportion of heavy weight seeds and led to a significant increase in the mean dry weight. Germination success, germination rate and the root : shoot ratio of light weight seeds were reduced, while heavy weight seed did not appear to be affected by elevated temperatures. Finally, germinating seeds per unit area was reduced by increased temperature. The reduction in the number of germinating seeds with increasing temperature implies that continued global warming will further constrain new grassland establishment of L. chinensis in the eastern regions of Eurasia.
Mutation in a primate-conserved retrotransposon reveals a noncoding RNA as a mediator of infantile encephalopathy
Authors: Cartault François , Munier Patrick , Benko Edgar , Desguerre Isabelle , Hanein Sylvain , Boddaert Nathalie , Bandiera Simonetta , Vellayoudom Jeanine , Krejbich-Trotot Pascale , Bintner Marc , Hoarau Jean-Jacques , Girard Muriel , Génin Emmanuelle , de Lonlay Pascale , Fourmaintraux Alain , Naville Magali , Rodriguez Diana , Feingold Josué , Renouil Michel , Munnich Arnold , Westhof Eric , Fähling Michael , Lyonnet Stanislas , Henrion-Caude Alexandra
Published: March 2012

The human genome is densely populated with transposons and transposon-like repetitive elements. Although the impact of these transposons and elements on human genome evolution is recognized, the significance of subtle variations in their sequence remains mostly unexplored. Here we report homozygosity mapping of an infantile neurodegenerative disease locus in a genetic isolate. Complete DNA sequencing of the 400-kb linkage locus revealed a point mutation in a primate-specific retrotransposon that was transcribed as part of a unique noncoding RNA, which was expressed in the brain. In vitro knockdown of this RNA increased neuronal apoptosis, consistent with the inappropriate dosage of this RNA in vivo and with the phenotype. Moreover, structural analysis of the sequence revealed a small RNA-like hairpin that was consistent with the putative gain of a functional site when mutated. We show here that a mutation in a unique transposable element-containing RNA is associated with lethal encephalopathy, and we suggest that RNAs that harbor evolutionarily recent repetitive elements may play important roles in human brain development.
Reactive polymer enables efficient in vivo bioorthogonal chemistry
Authors: Devaraj Neal K. , Thurber Greg M. , Keliher Edmund J. , Marinelli Brett , Weissleder Ralph
Published: March 2012

There has been intense interest in the development of selective bioorthogonal reactions or “click” chemistry that can proceed in live animals. Until now however, most reactions still require vast surpluses of reactants because of steep temporal and spatial concentration gradients. Using computational modeling and design of pharmacokinetically optimized reactants, we have developed a predictable method for efficient in vivo click reactions. Specifically, we show that polymer modified tetrazines (PMT) are a key enabler for in vivo bioorthogonal chemistry based on the very fast and catalyst-free [4 + 2] tetrazine/
trans
-cyclooctene cycloaddition. Using fluorescent PMT for cellular resolution and
18
F labeled PMT for whole animal imaging, we show that cancer cell epitopes can be easily reacted in vivo. This generic strategy should help guide the design of future chemistries and find widespread use for different in vivo bioorthogonal applications, particularly in the biomedical sciences.
Metabolic labeling enables selective photocrosslinking of O-GlcNAc-modified proteins to their binding partners
Authors: Yu Seok-Ho , Boyce Michael , Wands Amberlyn M. , Bond Michelle R. , Bertozzi Carolyn R. , Kohler Jennifer J.
Published: March 2012

O-linked β-
N
-acetylglucosamine (O-GlcNAc) is a reversible posttranslational modification found on hundreds of nuclear and cytoplasmic proteins in higher eukaryotes. Despite its ubiquity and essentiality in mammals, functional roles for the O-GlcNAc modification remain poorly defined. Here we develop a combined genetic and chemical approach that enables introduction of the diazirine photocrosslinker onto the O-GlcNAc modification in cells. We engineered mammalian cells to produce diazirine-modified O-GlcNAc by expressing a mutant form of UDP-GlcNAc pyrophosphorylase and subsequently culturing these cells with a cell-permeable, diazirine-modified form of GlcNAc-1-phosphate. Irradiation of cells with UV light activated the crosslinker, resulting in formation of covalent bonds between O-GlcNAc-modified proteins and neighboring molecules, which could be identified by mass spectrometry. We used this method to identify interaction partners for the O-GlcNAc-modified FG-repeat nucleoporins. We observed crosslinking between FG-repeat nucleoporins and nuclear transport factors, suggesting that O-GlcNAc residues are intimately associated with essential recognition events in nuclear transport. Further, we propose that the method reported here could find widespread use in investigating the functional consequences of O-GlcNAcylation.
Wnt/β-catenin signaling requires interaction of the Dishevelled DEP domain and C terminus with a discontinuous motif in Frizzled
Authors: Tauriello Daniele V. F. , Jordens Ingrid , Kirchner Katharina , Slootstra Jerry W. , Kruitwagen Tom , Bouwman Britta A. M. , Noutsou Maria , Rüdiger Stefan G. D. , Schwamborn Klaus , Schambony Alexandra , Maurice Madelon M.
Published: March 2012

Wnt binding to members of the seven-span transmembrane Frizzled (Fz) receptor family controls essential cell fate decisions and tissue polarity during development and in adulthood. The Fz-mediated membrane recruitment of the cytoplasmic effector Dishevelled (Dvl) is a critical step in Wnt/β-catenin signaling initiation, but how Fz and Dvl act together to drive downstream signaling events remains largely undefined. Here, we use an Fz peptide-based microarray to uncover a mechanistically important role of the bipartite Dvl DEP domain and C terminal region (DEP-C) in binding a three-segmented discontinuous motif in Fz. We show that cooperative use of two conserved motifs in the third intracellular loop and the classic C-terminal motif of Fz is required for DEP-C binding and Wnt-induced β-catenin activation in cultured cells and
Xenopus
embryos. Within the complex, the Dvl DEP domain mainly binds the Fz C-terminal tail, whereas a short region at the Dvl C-terminal end is required to bind the Fz third loop and stabilize the Fz-Dvl interaction. We conclude that Dvl DEP-C binding to Fz is a key event in Wnt-mediated signaling relay to β-catenin. The discontinuous nature of the Fz-Dvl interface may allow for precise regulation of the interaction in the control of Wnt-dependent cellular responses.
Resting-state glutamate level in the anterior cingulate predicts blood-oxygen level-dependent response to cognitive control
Authors: Falkenberg Liv E. , Westerhausen René , Specht Karsten , Hugdahl Kenneth
Published: March 2012

The dorsal anterior cingulate cortex (dACC) is a core structure for the governing of cognitive control, and recent studies have shown that interindividual differences in dACC anatomy are associated with corresponding differences in the ability for cognitive control. However, individuals differ not only in anatomical features of dACC, but also exhibit substantial variability regarding the biochemical characteristics of the dACC. In this study, we combined magnetic resonance spectroscopy (
1
H-MRS) and functional magnetic resonance imaging (fMRI), finding that interindividual differences of glutamate levels in the dACC during resting-state predict the strength of the blood-oxygen level-dependent (BOLD) response to a task requiring cognitive control. This relationship was observed in the retrosplenial cortex, the orbitofrontal cortex, the inferior parietal lobe, and the basal ganglia. More specifically, individuals with low resting-state glutamate levels in the dACC showed an increased BOLD response when the task demands were high, whereas high-glutamate individuals showed the opposite pattern of an increased BOLD response when the task demands were low. Thus, we show here that individual variability of glutamate levels is directly related to how the brain implements cognitive control.
Correcting human mitochondrial mutations with targeted RNA import
Authors: Wang Geng , Shimada Eriko , Zhang Jin , Hong Jason S. , Smith Geoffrey M. , Teitell Michael A. , Koehler Carla M.
Published: March 2012

Mutations in the human mitochondrial genome are implicated in neuromuscular diseases, metabolic defects, and aging. An efficient and simple mechanism for neutralizing deleterious mitochondrial DNA (mtDNA) alterations has unfortunately remained elusive. Here, we report that a 20-ribonucleotide stem-loop sequence from the
H1
RNA, the RNA component of the human RNase P enzyme, appended to a nonimported RNA directs the import of the resultant RNA fusion transcript into human mitochondria. The methodology is effective for both noncoding RNAs, such as tRNAs, and mRNAs. The RNA import component, polynucleotide phosphorylase (PNPASE), facilitates transfer of this hybrid RNA into the mitochondrial matrix. In addition, nucleus-encoded mRNAs for mitochondrial proteins, such as the mRNA of human mitochondrial ribosomal protein S12 (
MRPS12
), contain regulatory sequences in their 3′-untranslated region (UTR) that confers localization to the mitochondrial outer membrane, which is postulated to aid in protein translocation after translation. We show that for some mitochondrial-encoded transcripts, such as
COX2
, a 3′-UTR localization sequence is not required for mRNA import, whereas for corrective mitochondrial-encoded tRNAs, appending the 3′-UTR localization sequence was essential for efficient fusion-transcript translocation into mitochondria. In vivo, functional defects in mitochondrial RNA (mtRNA) translation and cell respiration were reversed in two human disease lines. Thus, this study indicates that a wide range of RNAs can be targeted to mitochondria by appending a targeting sequence that interacts with PNPASE, with or without a mitochondrial localization sequence, providing an exciting, general approach for overcoming mitochondrial genetic disorders.
Myeloid leukemia factor is a conserved regulator of RUNX transcription factor activity involved in hematopoiesis
Authors: Bras Stéphanie , Martin-Lannerée Séverine , Gobert Vanessa , Augé Benoît , Breig Osman , Sanial Matthieu , Yamaguchi Masamitsu , Haenlin Marc , Plessis Anne , Waltzer Lucas
Published: March 2012

Defining the function of the genes that, like
RUNX1
, are deregulated in blood cell malignancies represents an important challenge. Myeloid leukemia factors (MLFs) constitute a poorly characterized family of conserved proteins whose founding member, MLF1, has been associated with acute myeloid leukemia in humans. To gain insight into the functions of this family, we investigated the role of the
Drosophila
MLF homolog during blood cell development. Here we report that
mlf
controls the homeostasis of the
Drosophila
hematopoietic system. Notably,
mlf
participates in a positive feedback loop to fine tune the activity of the RUNX transcription factor Lozenge (LZ) during development of the crystal cells, one of the two main blood cell lineages in
Drosophila
. At the molecular level, our data in cell cultures and in vivo strongly suggest that MLF controls the number of crystal cells by protecting LZ from degradation. Remarkably, it appears that the human MLF1 protein can substitute for MLF in the crystal cell lineage. In addition, MLF stabilizes the human oncogenic fusion protein RUNX1-ETO and is required for RUNX1-ETO–induced blood cell disorders in a
Drosophila
model of leukemia. Finally, using the human leukemic blood cell line Kasumi-1, we show that
MLF1
depletion impairs RUNX1-ETO accumulation and reduces RUNX1-ETO–dependent proliferation. Thus, we propose that the regulation of RUNX protein levels is a conserved feature of MLF family members that could be critical for normal and pathological blood cell development.
Autism-like socio-communicative deficits and stereotypies in mice lacking heparan sulfate
Authors: Irie Fumitoshi , Badie-Mahdavi Hedieh , Yamaguchi Yu
Published: March 2012

Heparan sulfate regulates diverse cell-surface signaling events, and its roles in the development of the nervous system recently have been increasingly uncovered by studies using genetic models carrying mutations of genes encoding enzymes for its synthesis. On the other hand, the role of heparan sulfate in the physiological function of the adult brain has been poorly characterized, despite several pieces of evidence suggesting its role in the regulation of synaptic function. To address this issue, we eliminated heparan sulfate from postnatal neurons by conditionally inactivating
Ext1
, the gene encoding an enzyme essential for heparan sulfate synthesis. Resultant conditional mutant mice show no detectable morphological defects in the cytoarchitecture of the brain. Remarkably, these mutant mice recapitulate almost the full range of autistic symptoms, including impairments in social interaction, expression of stereotyped, repetitive behavior, and impairments in ultrasonic vocalization, as well as some associated features. Mapping of neuronal activation by c-Fos immunohistochemistry demonstrates that neuronal activation in response to social stimulation is attenuated in the amygdala in these mice. Electrophysiology in amygdala pyramidal neurons shows an attenuation of excitatory synaptic transmission, presumably because of the reduction in the level of synaptically localized AMPA-type glutamate receptors. Our results demonstrate that heparan sulfate is critical for normal functioning of glutamatergic synapses and that its deficiency mediates socio-communicative deficits and stereotypies characteristic for autism.
Soluble oligomerization provides a beneficial fitness effect on destabilizing mutations
Authors: Bershtein Shimon , Mu Wanmeng , Shakhnovich Eugene I.
Published: March 2012

Mutations create the genetic diversity on which selective pressures can act, yet also create structural instability in proteins. How, then, is it possible for organisms to ameliorate mutation-induced perturbations of protein stability while maintaining biological fitness and gaining a selective advantage? Here we used site-specific chromosomal mutagenesis to introduce a selected set of mostly destabilizing mutations into
folA
—an essential chromosomal gene of
Escherichia coli
encoding dihydrofolate reductase (DHFR)—to determine how changes in protein stability, activity, and abundance affect fitness. In total, 27
E. coli
strains carrying mutant DHFR were created. We found no significant correlation between protein stability and its catalytic activity nor between catalytic activity and fitness in a limited range of variation of catalytic activity observed in mutants. The stability of these mutants is strongly correlated with their intracellular abundance, suggesting that protein homeostatic machinery plays an active role in maintaining intracellular concentrations of proteins. Fitness also shows a significant correlation with intracellular abundance of soluble DHFR in cells growing at 30 °C. At 42 °C, the picture was mixed, yet remarkable: A few strains carrying mutant DHFR proteins aggregated, rendering them nonviable, but, intriguingly, the majority exhibited fitness higher than wild type. We found that mutational destabilization of DHFR proteins in
E. coli
is counterbalanced at 42 °C by their soluble oligomerization, thereby restoring structural stability and protecting against aggregation.
Forecasting sudden changes in environmental pollution patterns
Authors: Olascoaga María J. , Haller George
Published: March 2012

The lack of reliable forecasts for the spread of oceanic and atmospheric contamination hinders the effective protection of the ecosystem, society, and the economy from the fallouts of environmental disasters. The consequences can be dire, as evidenced by theDeepwater Horizonoil spill in the Gulf of Mexico in 2010. We present a methodology to predict major short-term changes in environmental contamination patterns, such as oil spills in the ocean and ash clouds in the atmosphere. Our approach is based on new mathematical results on the objective (frame-independent) identification of key material surfaces that drive tracer mixing in unsteady, finite-time flow data. Some of these material surfaces, known as Lagrangian coherent structures (LCSs), turn out to admit highly attracting cores that lead to inevitable material instabilities even under future uncertainties or unexpected perturbations to the observed flow. These LCS cores have the potential to forecast imminent shape changes in the contamination pattern, even before the instability builds up and brings large masses of water or air into motion. Exploiting this potential, the LCS-core analysis developed here provides a model-independent forecasting scheme that relies only on already observed or validated flow velocities at the time the prediction is made. We use this methodology to obtain high-precision forecasts of two major instabilities that occurred in the shape of theDeepwater Horizonoil spill. This is achieved using simulated surface currents preceding the prediction times and assuming that the oil behaves as a passive tracer.
Cytotoxicity of a Ti(IV) compound is independent of serum proteins
Authors: Tinoco Arthur D. , Thomas Horatio R. , Incarvito Christopher D. , Saghatelian Alan , Valentine Ann M.
Published: March 2012

Titanium(IV) compounds are excellent anticancer drug candidates, but they have yet to find success in clinical applications. A major limitation in developing further compounds has been a general lack of understanding of the mechanism governing their bioactivity. To determine factors necessary for bioactivity, we tested the cytotoxicity of different ligand compounds in conjunction with speciation studies and mass spectrometry bioavailability measurements. These studies demonstrated that the Ti(IV) compound of
N
,
N
′
-
di(
o
-hydroxybenzyl)ethylenediamine-
N
,
N
′
-
diacetic acid (HBED) is cytotoxic to A549 lung cancer cells, unlike those of citrate and naphthalene-2,3-diolate. Although serum proteins are implicated in the activity of Ti(IV) compounds, we found that these interactions do not play a role in [TiO(HBED)]
−
activity. Subsequent compound characterization revealed ligand properties necessary for activity. These findings establish the importance of the ligand in the bioactivity of Ti(IV) compounds, provides insights for developing next-generation Ti(IV) anticancer compounds, and reveal [TiO(HBED)]
−
as a unique candidate anticancer compound.
Synaptic evidence for the efficacy of spaced learning
Authors: Kramár Enikö A. , Babayan Alex H. , Gavin Cristin F. , Cox Conor D. , Jafari Matiar , Gall Christine M. , Rumbaugh Gavin , Lynch Gary
Published: March 2012

The superiority of spaced vs. massed training is a fundamental feature of learning. Here, we describe unanticipated timing rules for the production of long-term potentiation (LTP) in adult rat hippocampal slices that can account for one temporal segment of the spaced trials phenomenon. Successive bouts of naturalistic theta burst stimulation of field CA1 afferents markedly enhanced previously saturated LTP if spaced apart by 1 h or longer, but were without effect when shorter intervals were used. Analyses of F-actin-enriched spines to identify potentiated synapses indicated that the added LTP obtained with delayed theta trains involved recruitment of synapses that were “missed” by the first stimulation bout. Single spine glutamate-uncaging experiments confirmed that less than half of the spines in adult hippocampus are primed to undergo plasticity under baseline conditions, suggesting that intrinsic variability among individual synapses imposes a repetitive presentation requirement for maximizing the percentage of potentiated connections. We propose that a combination of local diffusion from initially modified spines coupled with much later membrane insertion events dictate that the repetitions be widely spaced. Thus, the synaptic mechanisms described here provide a neurobiological explanation for one component of a poorly understood, ubiquitous aspect of learning.
Tfb6, a previously unidentified subunit of the general transcription factor TFIIH, facilitates dissociation of Ssl2 helicase after transcription initiation
Authors: Murakami Kenji , Gibbons Brian J. , Davis Ralph E. , Nagai Shigeki , Liu Xin , Robinson Philip J. J. , Wu Tinghe , Kaplan Craig D. , Kornberg Roger D.
Published: March 2012

General transcription factor TFIIH, previously described as a 10-subunit complex, is essential for transcription and DNA repair. An eleventh subunit now identified, termed Tfb6, exhibits 45% sequence similarity to human nuclear mRNA export factor 5. Tfb6 dissociates from TFIIH as a heterodimer with the Ssl2 subunit, a DNA helicase that drives promoter melting for the initiation of transcription. Tfb6 does not, however, dissociate Ssl2 from TFIIH in the context of a fully assembled transcription preinitiation complex. Our findings suggest a dynamic state of Ssl2, allowing its engagement in multiple cellular processes.
Multiple organellar RNA editing factor (MORF) family proteins are required for RNA editing in mitochondria and plastids of plants
Authors: Takenaka Mizuki , Zehrmann Anja , Verbitskiy Daniil , Kugelmann Matthias , Härtel Barbara , Brennicke Axel
Published: March 2012

RNA editing in plastids and mitochondria of flowering plants changes hundreds of selected cytidines to uridines, mostly in coding regions of mRNAs. Specific sequences around the editing sites are presumably recognized by up to 200 pentatricopeptide repeat (PPR) proteins. The here identified family of multiple organellar RNA editing factor (MORF) proteins provides additional components of the RNA editing machinery in both plant organelles. Two MORF proteins are required for editing in plastids; at least two are essential for editing in mitochondria. The loss of a MORF protein abolishes or lowers editing at multiple sites, many of which are addressed individually by PPR proteins. In plastids, both MORF proteins are required for complete editing at almost all sites, suggesting a heterodimeric complex. In yeast two-hybrid and pull-down assays, MORF proteins can connect to form hetero- and homodimers. Furthermore, MORF proteins interact selectively with PPR proteins, establishing a more complex editosome in plant organelles than previously thought.
Plasmodesmata formation and cell-to-cell transport are reduced in
decreased size exclusion limit 1
during embryogenesis in
Arabidopsis
Authors: Xu Min , Cho Euna , Burch-Smith Tessa M. , Zambryski Patricia C.
Published: March 2012

In plants, plasmodesmata (PD) serve as channels for micromolecular and macromolecular cell-to-cell transport. Based on structure, PD in immature tissues are classified into two types, simple and branched (X- and Y-shaped) or twinned. The maximum size of molecules capable of PD transport defines PD aperture, known as the PD size exclusion limit. Here we report an
Arabidopsis
mutation,
decreased size exclusion limit1
(
dse1
), that exhibits reduced cell-to-cell transport of the small (524 Da) fluorescent tracer 8-hydroxypyrene-1,3,6-trisulfonic acid at the midtorpedo stage of embryogenesis. Correspondingly, the fraction of X- and Y-shaped and twinned PD was reduced in
dse1
embryos compared with WT embryos at this stage, suggesting that the frequency of PD is related to transport capability.
dse1
is caused by a point mutation in At4g29860 (previously termed
TANMEI
) at the last donor splice site of its transcript, resulting in alternative splicing in both the first intron and the last intron. AtDSE1 is a conserved eukaryotic 386-aa WD-repeat protein critical for
Arabidopsis
morphogenesis and reproduction. Similar to its homologs in mouse, null mutants are embryo-lethal. The weak loss-of-function mutant
dse1
exhibits pleiotropic phenotypes, including retarded vegetative growth, delayed flowering time, dysfunctional male and female organs, and delayed senescence. Finally, silencing of
DSE1
in
Nicotiana benthamiana
leaves leads to reduced movement of GFP fused to tobacco mosaic virus movement protein. Thus, DSE1 is important for regulating PD transport between plant cells.
The taxonomy of the genus Capsicum.
Authors: Eshbaugh W. H.
Published: March 2012

This chapter covers the origin, evolution, taxonomy and geographical distribution (once endemic to the Americas, but is now distributed throughout the world, including Asia and Africa) of domesticated and wild Capsicum species, including C. annuum var. annuum, C. chinense, C. frutescens, C. baccatum var. pendulum and C. pubescens. A key to the domesticated species of Capsicum is presented.
Tissue culture of Capsicum species.
Authors: Santana-Buzzy N. , Bello-Bello J. J. , Iglesias-Andreu L. , Zúñiga-Aguilar J. J. , Canto-Flick A. , Avilés-Viñas S. A. , Lecona-Guzmán C. A. , Solís-Marroquín D. , Gómez-Uc E. , Balam-Uc E. , Arcos-Ortega G. F. , Mijangos-Cortés J. O.
Published: March 2012

This chapter focuses on various aspects of the in vitro culture of pepper (Capsicum spp.), including the effects of genotype and explant on regeneration ability, the physiological changes that occur during in vitro organogenesis and somatic embryogenesis, and the application of in vitro culture in pepper genetic improvement through haploid culture and genetic engineering.
Transplanters for use in pepper production.
Authors: Kumar G. V. P. , Hifjur Raheman Hifjur Raheman
Published: March 2012

This chapter describes the components (trash cutting devices, furrow openers, soil covering and soil packing devices, planting unit, and seedling pick-up unit) and functions of transplanters used in pepper (Capsicum spp.) production, and provides an overview of recent advances in the design of transplanters, and on the transplanting requirements of peppers and mechanical transplanters.
Pepper fertilization and irrigation management.
Authors: Santos B. M.
Published: March 2012

This chapter briefly discusses the major physiological functions of macronutrients and micronutrients in plants (nitrogen, phosphorus, potassium, calcium, magnesium, sulfur, iron, manganese, zinc, boron, copper, molybdenum, chlorine and nickel), and describes symptoms of deficiency in these nutrients. The nutritional and water requirements of pepper (Capsicum spp.), and factors affecting fertilizer application and irrigation practices in pepper production are also covered.
Cropping systems for field production.
Authors: Kahn B. A. , Leskovar D. I.
Published: March 2012

This chapter provides an overview of several components of cropping systems for the production of peppers (Capsicum annuum and C. frutescens) in the field. Soil preparation (bedding and mulching), plant density and spacing, plant management (use of row covers and low tunnels, pruning, and plant training and support), and specialized cropping systems (systems that modify tillage, intercropping, and ratoon cropping) are specifically covered.
Physiology of metabolites.
Authors: Frary A. , Frary A.
Published: March 2012

This chapter provides an overview of recent research on the effects of genotype fruit development and growing conditions on the synthesis and concentrations of the following metabolites in pepper (Capsicum spp.): antioxidants, carotenoids, phenolic compounds, capsaicinoids, flavonoids and vitamin C.
Postharvest requirements of peppers.
Authors: Gil M. I. , Tudela J. A.
Published: March 2012

This chapter discusses the following aspects of postharvest handling of pepper (Capsicum spp.) fruits: pre-sizing, sorting and selection; pre-cooling; storage conditions; postharvest quality losses; water loss; decay; prevention of postharvest quality losses; controlled atmosphere and modified atmosphere packaging; and preparation of fresh-cut peppers.
Greenhouse pepper production economics.
Authors: Chaudhary G. N. , Mirza M.
Published: March 2012

This chapter covers the economics of greenhouse pepper (Capsicum spp.) production, describing the effects of production factors (propagation, planting density, and plant management during the production cycle) on profitability. An overview of greenhouse pepper production costs and returns in Alberta, Canada, is presented.
Effects of Decelerating and Accelerating Flows on Juvenile Salmonid Behavior
Authors: Enders Eva C. , Gessel Michael H. , Anderson James J. , Williams John G.
Published: March 2012

Migratory and resident fish species have evolved inherent flight responses to avoid potentially harmful situations. At many dams, fish screens or other structures have been installed to guide fish away from turbines or attract them to routes that will result in higher survival. Avoidance responses of fish to rapidly decelerating and accelerating flows at these structures have been repeatedly observed and can result in ineffective fish guidance. By using controlled flume experiments, we analyzed the avoidance behavior of actively migrating spring Chinook salmon Oncorhynchus tshawytscha smolts in relation to flow decelerations and accelerations. As smolts drifted into areas with decreasing velocities, they actively swam into the current; the larger was the change in water velocity with distance (spatial velocity gradient [SVG]), the faster was the swimming speed exhibited by smolts. Under accelerating flows, the response velocity varied significantly with flow conditions, but the median SVG at which smolts displayed an avoidance response was similar over all flows tested. For both decelerating and accelerating flows, the avoidance response occurred at an SVG of approximately 1 cm·s−1·cm−1. We suggest that this threshold is in part fixed by the energetically optimum swimming speed of the fish (∼1 body length/s).
Classical Pattern Recall Tests and the Prospective Nature of Expert Performance
Authors: Gorman Adam D. , Abernethy Bruce , Farrow Damian
Published: March 2012

It is well established that experts are particularly adept at recalling and/or recognizing the key features of domain-relevant patterns. We compared the recall performance of expert and novice basketball players when viewing static and moving patterns. A novel method of analysis was used where the accuracy of the participants in recalling player positions was compared to actual player positions both at the final frame of pattern presentation and at 50 successive 40 ms increments thereafter. Experts encoded the locations of the players in both the static and moving patterns significantly further in advance of their actual finishing point than did nonexperts. Experts' use of an anticipatory encoding process, which was of a magnitude unmatched by nonexperts, suggests that many previous investigations may have underestimated the extent of the expert advantage in pattern recall.
Balanced Ero1 activation and inactivation establishes ER redox homeostasis
Authors: Kim Sunghwan , Sideris Dionisia P. , Sevier Carolyn S. , Kaiser Chris A.
Published: March 2012

The endoplasmic reticulum (ER) provides an environment optimized for oxidative protein folding through the action of Ero1p, which generates disulfide bonds, and Pdi1p, which receives disulfide bonds from Ero1p and transfers them to substrate proteins. Feedback regulation of Ero1p through reduction and oxidation of regulatory bonds within Ero1p is essential for maintaining the proper redox balance in the ER. In this paper, we show that Pdi1p is the key regulator of Ero1p activity. Reduced Pdi1p resulted in the activation of Ero1p by direct reduction of Ero1p regulatory bonds. Conversely, upon depletion of thiol substrates and accumulation of oxidized Pdi1p, Ero1p was inactivated by both autonomous oxidation and Pdi1p-mediated oxidation of Ero1p regulatory bonds. Pdi1p responded to the availability of free thiols and the relative levels of reduced and oxidized glutathione in the ER to control Ero1p activity and ensure that cells generate the minimum number of disulfide bonds needed for efficient oxidative protein folding.
The Mst1 and Mst2 kinases control activation of rho family GTPases and thymic egress of mature thymocytes
Authors: Mou Fan , Praskova Maria , Xia Fan , Van Buren Denille , Hock Hanno , Avruch Joseph , Zhou Dawang
Published: March 2012

The Mst1 kinase is an important regulator of murine T cell adhesion, migration, proliferation, and apoptosis. In this study, we analyze mice lacking both Mst1 and Mst2 in hematopoietic cells. Compared with wild-type mice, these double knockout (DKO) mice exhibit a severe reduction in the number of mature T cells in the circulation and in secondary lymphoid organs (SLOs). CD4+CD8− and CD4−CD8+ single-positive (SP) thymocytes in DKO mice resemble mature T cells of wild-type mice but undergo excessive apoptosis, and their egress from the thymus is reduced by >90%. Even when placed directly in the circulation, DKO SP thymocytes failed to enter SLOs. In SP thymocytes, deficiency of Mst1 and Mst2 abolished sphingosine-1 phosphate– and CCL21-induced Mob1 phosphorylation, Rac1 and RhoA GTP charging, and subsequent cell migration. When phosphorylated by Mst1 or Mst2, Mob1 binds and activates the Rac1 guanyl nucleotide exchanger Dock8, which is abundant in the thymus. Thus, the Mst1 and Mst2 kinases control Rho GTPase activation and the migratory responses of SP thymocytes.
The voltage dependence of the TMEM16B/anoctamin2 calcium-activated chloride channel is modified by mutations in the first putative intracellular loop
Authors: Cenedese Valentina , Betto Giulia , Celsi Fulvio , Cherian O. Lijo , Pifferi Simone , Menini Anna
Published: March 2012

Ca2+-activated Cl− channels (CaCCs) are involved in several physiological processes. Recently, TMEM16A/anoctamin1 and TMEM16B/anoctamin2 have been shown to function as CaCCs, but very little information is available on the structure–function relations of these channels. TMEM16B is expressed in the cilia of olfactory sensory neurons, in microvilli of vomeronasal sensory neurons, and in the synaptic terminals of retinal photoreceptors. Here, we have performed the first site-directed mutagenesis study on TMEM16B to understand the molecular mechanisms of voltage and Ca2+ dependence. We have mutated amino acids in the first putative intracellular loop and measured the properties of the wild-type and mutant TMEM16B channels expressed in HEK 293T cells using the whole cell voltage-clamp technique in the presence of various intracellular Ca2+ concentrations. We mutated E367 into glutamine or deleted the five consecutive glutamates 386EEEEE390 and 399EYE401. The EYE deletion did not significantly modify the apparent Ca2+ dependence nor the voltage dependence of channel activation. E367Q and deletion of the five glutamates did not greatly affect the apparent Ca2+ affinity but modified the voltage dependence, shifting the conductance–voltage relations toward more positive voltages. These findings indicate that glutamates E367 and 386EEEEE390 in the first intracellular putative loop play an important role in the voltage dependence of TMEM16B, thus providing an initial structure–function study for this channel.