bluuebunny/crossref_metadata_2025 huggingface dataset:
A shift toward birthing relatively large infants early in human evolution
Authors: DeSilva Jeremy M.
Published: January 2011

It has long been argued that modern human mothers give birth to proportionately larger babies than apes do. Data presented here from human and chimpanzee infant:mother dyads confirm this assertion: humans give birth to infants approximately 6% of their body mass, compared with approximately 3% for chimpanzees, even though the female body weights of the two species are moderately convergent. Carrying a relatively large infant both pre- and postnatally has important ramifications for birthing strategies, social systems, energetics, and locomotion. However, it is not clear when the shift to birthing large infants occurred over the course of human evolution. Here, known and often conserved relationships between adult brain mass, neonatal brain mass, and neonatal body mass in anthropoids are used to estimate birthweights of extinct hominid taxa. These estimates are resampled with direct measurements of fossil postcrania from female hominids, and also compared with estimates of female body mass to assess when human-like infant:mother mass ratios (IMMRs) evolved. The results of this study suggest that 4.4-Myr-oldArdipithecuspossessed IMMRs similar to those found in African apes, indicating that a low IMMR is the primitive condition in hominids.Australopithecusfemales, in contrast, had significantly heavier infants compared with dimensions of the femoral head (n= 7) and ankle (n= 7) than what is found in chimpanzees, and are estimated to have birthed neonates more than 5% of their body mass. Carrying such proportionately large infants may have limited arboreality inAustralopithecusfemales and may have selected for alloparenting behavior earlier in human evolution than previously thought.
Recovering sound sources from embedded repetition
Authors: McDermott Josh H. , Wrobleski David , Oxenham Andrew J.
Published: January 2011

Cocktail parties and other natural auditory environments present organisms with mixtures of sounds. Segregating individual sound sources is thought to require prior knowledge of source properties, yet these presumably cannot be learned unless the sources are segregated first. Here we show that the auditory system can bootstrap its way around this problem by identifying sound sources as repeating patterns embedded in the acoustic input. Due to the presence of competing sounds, source repetition is not explicit in the input to the ear, but it produces temporal regularities that listeners detect and use for segregation. We used a simple generative model to synthesize novel sounds with naturalistic properties. We found that such sounds could be segregated and identified if they occurred more than once across different mixtures, even when the same sounds were impossible to segregate in single mixtures. Sensitivity to the repetition of sound sources can permit their recovery in the absence of other segregation cues or prior knowledge of sounds, and could help solve the cocktail party problem.
Nutrient regime shift in the western North Atlantic indicated by compound-specific
δ
15
N of deep-sea gorgonian corals
Authors: Sherwood Owen A. , Lehmann Moritz F. , Schubert Carsten J. , Scott David B. , McCarthy Matthew D.
Published: January 2011

Despite the importance of the nitrogen (N) cycle on marine productivity, little is known about variability in N sources and cycling in the ocean in relation to natural and anthropogenic climate change. Beyond the last few decades of scientific observation, knowledge depends largely on proxy records derived from nitrogen stable isotopes (
δ
15
N) preserved in sediments and other bioarchives. Traditional bulk
δ
15
N measurements, however, represent the combined influence of N source and subsequent trophic transfers, often confounding environmental interpretation. Recently, compound-specific analysis of individual amino acids (
δ
15
N-AA) has been shown as a means to deconvolve trophic level versus N source effects on the
δ
15
N variability of bulk organic matter. Here, we demonstrate the first use of
δ
15
N-AA in a paleoceanographic study, through analysis of annually secreted growth rings preserved in the organic endoskeletons of deep-sea gorgonian corals. In the Northwest Atlantic off Nova Scotia, coral
δ
15
N is correlated with increasing presence of subtropical versus subpolar slope waters over the twentieth century. By using the new
δ
15
N-AA approach to control for variable trophic processing, we are able to interpret coral bulk
δ
15
N values as a proxy for nitrate source and, hence, slope water source partitioning. We conclude that the persistence of the warm, nutrient-rich regime since the early 1970s is largely unique in the context of the last approximately 1,800 yr. This evidence suggests that nutrient variability in this region is coordinated with recent changes in global climate and underscores the broad potential of
δ
15
N-AA for paleoceanographic studies of the marine N cycle.
Selenoprotein TRXR-1 and GSR-1 are essential for removal of old cuticle during molting in
Caenorhabditis elegans
Authors: Stenvall Jörgen , Fierro-González Juan Carlos , Swoboda Peter , Saamarthy Karunakar , Cheng Qing , Cacho-Valadez Briseida , Arnér Elias S. J. , Persson Olof P. , Miranda-Vizuete Antonio , Tuck Simon
Published: January 2011

Selenoproteins, in particular thioredoxin reductase, have been implicated in countering oxidative damage occurring during aging but the molecular functions of these proteins have not been extensively investigated in different animal models. Here we demonstrate that TRXR-1 thioredoxin reductase, the sole selenoprotein in
Caenorhabditis elegans
, does not protect against acute oxidative stress but functions instead together with GSR-1 glutathione reductase to promote the removal of old cuticle during molting. We show that the oxidation state of disulfide groups in the cuticle is tightly regulated during the molting cycle, and that when
trxr-1
and
gsr-1
function is reduced, disulfide groups in the cuticle remain oxidized. A selenocysteine-to-cysteine TRXR-1 mutant fails to rescue molting defects. Furthermore, worms lacking SELB-1, the
C. elegans
homolog of
Escherichia coli
SelB or mammalian EFsec, a translation elongation factor known to be specific for selenocysteine in
E. coli
, fail to incorporate selenocysteine, and display the same phenotype as those lacking
trxr-1
. Thus, TRXR-1 function in the reduction of old cuticle is strictly selenocysteine dependent in the nematode. Exogenously supplied reduced glutathione reduces disulfide groups in the cuticle and induces apolysis, the separation of old and new cuticle, strongly suggesting that molting involves the regulated reduction of cuticle components driven by TRXR-1 and GSR-1. Using dauer larvae, we demonstrate that aged worms have a decreased capacity to molt, and decreased expression of GSR-1. Together, our results establish a function for the selenoprotein TRXR-1 and GSR-1 in the removal of old cuticle from the surface of epidermal cells.
RNS2, a conserved member of the RNase T2 family, is necessary for ribosomal RNA decay in plants
Authors: Hillwig Melissa S. , Contento Anthony L. , Meyer Alexander , Ebany Danielle , Bassham Diane C. , MacIntosh Gustavo C.
Published: January 2011

RNase T2 enzymes are conserved in most eukaryotic genomes, and expression patterns and phylogenetic analyses suggest that they may carry out an important housekeeping role. However, the nature of this role has been elusive. Here we show that RNS2, an intracellular RNase T2 from
Arabidopsis thaliana
, is essential for normal ribosomal RNA recycling. This enzyme is the main endoribonuclease activity in plant cells and localizes to the endoplasmic reticulum (ER), ER-derived structures, and vacuoles. Mutants lacking RNS2 activity accumulate RNA intracellularly, and rRNA in these mutants has a longer half-life. Normal rRNA turnover seems essential to maintain cell homeostasis because
rns2
mutants display constitutive autophagy. We propose that RNS2 is part of a process that degrades rRNA to recycle its components. This process appears to be conserved in all eukaryotes.
A structural and functional ground plan for neurons in the hindbrain of zebrafish
Authors: Kinkhabwala Amina , Riley Michael , Koyama Minoru , Monen Joost , Satou Chie , Kimura Yukiko , Higashijima Shin-ichi , Fetcho Joseph
Published: January 2011

The vertebrate hindbrain contains various sensory-motor networks controlling movements of the eyes, jaw, head, and body. Here we show that stripes of neurons with shared neurotransmitter phenotype that extend throughout the hindbrain of young zebrafish reflect a broad underlying structural and functional patterning. The neurotransmitter stripes contain cell types with shared gross morphologies and transcription factor markers. Neurons within a stripe are stacked systematically by extent and location of axonal projections, input resistance, and age, and are recruited along the axis of the stripe during behavior. The implication of this pattern is that the many networks in hindbrain are constructed from a series of neuronal components organized into stripes that are ordered from top to bottom according to a neuron's age, structural and functional properties, and behavioral roles. This simple organization probably forms a foundation for the construction of the networks underlying the many behaviors produced by the hindbrain.
Mapping a sensory-motor network onto a structural and functional ground plan in the hindbrain
Authors: Koyama Minoru , Kinkhabwala Amina , Satou Chie , Higashijima Shin-ichi , Fetcho Joseph
Published: January 2011

The hindbrain of larval zebrafish contains a relatively simple ground plan in which the neurons throughout it are arranged into stripes that represent broad neuronal classes that differ in transmitter identity, morphology, and transcription factor expression. Within the stripes, neurons are stacked continuously according to age as well as structural and functional properties, such as axonal extent, input resistance, and the speed at which they are recruited during movements. Here we address the question of how particular networks among the many different sensory-motor networks in hindbrain arise from such an orderly plan. We use a combination of transgenic lines and pairwise patch recording to identify excitatory and inhibitory interneurons in the hindbrain network for escape behaviors initiated by the Mauthner cell. We map this network onto the ground plan to show that an individual hindbrain network is built by drawing components in predictable ways from the underlying broad patterning of cell types stacked within stripes according to their age and structural and functional properties. Many different specialized hindbrain networks may arise similarly from a simple early patterning.
Myelination transition zone astrocytes are constitutively phagocytic and have synuclein dependent reactivity in glaucoma
Authors: Nguyen Judy V. , Soto Ileana , Kim Keun-Young , Bushong Eric A. , Oglesby Ericka , Valiente-Soriano Francisco J. , Yang Zhiyong , Davis Chung-ha O. , Bedont Joseph L. , Son Janice L. , Wei John O. , Buchman Vladimir L. , Zack Donald J. , Vidal-Sanz Manuel , Ellisman Mark H. , Marsh-Armstrong Nicholas
Published: January 2011

Optic nerve head (ONH) astrocytes have been proposed to play both protective and deleterious roles in glaucoma. We now show that, within the postlaminar ONH myelination transition zone (MTZ), there are astrocytes that normally express Mac-2 (also known as Lgals3 or galectin-3), a gene typically expressed only in phagocytic cells. Surprisingly, even in healthy mice, MTZ and other ONH astrocytes constitutive internalize large axonal evulsions that contain whole organelles. In mouse glaucoma models, MTZ astrocytes further up-regulate Mac-2 expression. During glaucomatous degeneration, there are dystrophic processes in the retina and optic nerve, including the MTZ, which contain protease resistant γ-synuclein. The increased Mac-2 expression by MTZ astrocytes during glaucoma likely depends on this γ-synuclein, as mice lacking γ-synuclein fail to up-regulate Mac-2 at the MTZ after elevation of intraocular pressure. These results suggest the possibility that a newly discovered normal degradative pathway for axons might contribute to glaucomatous neurodegeneration.
Patterns of widespread decline in North American bumble bees
Authors: Cameron Sydney A. , Lozier Jeffrey D. , Strange James P. , Koch Jonathan B. , Cordes Nils , Solter Leellen F. , Griswold Terry L.
Published: January 2011

Bumble bees (Bombus) are vitally important pollinators of wild plants and agricultural crops worldwide. Fragmentary observations, however, have suggested population declines in several North American species. Despite rising concern over these observations in the United States, highlighted in a recent National Academy of Sciences report, a national assessment of the geographic scope and possible causal factors of bumble bee decline is lacking. Here, we report results of a 3-y interdisciplinary study of changing distributions, population genetic structure, and levels of pathogen infection in bumble bee populations across the United States. We compare current and historical distributions of eight species, compiling a database of >73,000 museum records for comparison with data from intensive nationwide surveys of >16,000 specimens. We show that the relative abundances of four species have declined by up to 96% and that their surveyed geographic ranges have contracted by 23–87%, some within the last 20 y. We also show that declining populations have significantly higher infection levels of the microsporidian pathogenNosema bombiand lower genetic diversity compared with co-occurring populations of the stable (nondeclining) species. Higher pathogen prevalence and reduced genetic diversity are, thus, realistic predictors of these alarming patterns of decline in North America, although cause and effect remain uncertain.
Ecological validity and 'white room effects'
Authors: Cicourel Aaron V.
Published: January 2011

Controlled elicitation of linguistic and psycholinguistic experimental data facilitate strong inferences about phonological, syntactic, semantic and pragmatic structures and functions, yet neglect the ecological validity of responses. Ecological validity in this paper refers to whether data gathered under controlled conditions are commensurate with routine problem solving and language use in natural settings. All methods produce "white room" effects that compromise data gathering and analysis. Unexamined folk knowledge and experiences also guide the investigator s interpretation of data from field research, laboratories, testing sessions, and target sentences. Story recall data from children in a combined second-third grade classroom and their narrative responses to cartoons without sound are used to illustrate ecological validity issues. The child's spontaneous, imaginative narratives about the story and cartoons resemble adult folk theory, and their semantic content reveal sociocultural knowledge essential for understanding subjects ' reasoning and information processing skills.
The pragmatic fallacies of the New Theory of Reference
Authors: Hintikka Jaakko
Published: January 2011

As is well known, according to the "new" theory of reference, the reference relation can be carried out by means of rigid designators whose relationship with the object they designate cannot be analyzed away. Moreover, the new theorists claim, the category of proper names in a natural language marks almost invariably rigid designators. In this paper, both claims are rejected. Using distinctions between the referential system (which determines which entities the primitive symbols of language refer to in each possible world) and the identification system (which determines which member of one world is identical with which member of another), and between two types of object identification (public and perspectival), it is argued that the use of a noun phrase as a rigid designator is predicated on the assumption that a language user knows who (or what) the noun phrase refers to in the actual world. The conclusion is that rigid designation is not a conceptually irreducible reference relation, nor are proper names always used as rigid designators.
Keeping an eye on gestures: Visual perception of gestures in face-to-face communication
Authors: Gullberg Marianne , Holmqvist Kenneth
Published: January 2011

Since listeners usually look at the speaker's face, gestural information has to be absorbed through peripheral visual perception. In the literature, it has been suggested that listeners look at gestures under certain circumstances: 1) when the articulation of the gesture is peripheral; 2) when the speech channel is insufficient for comprehension; and 3) when the speaker him- or herself indicates that the gesture is worthy of attention. The research here reported employs eye tracking techniques to study the perception of gestures in face-to-face interaction. The improved control over the listener's visual channel allows us to test the validity of the above claims. We present preliminary findings substantiating claims 1 and 3, and relate them to theoretical proposals in the literature and to the issue of how visual and cognitive attention are related.
Illocutions, implicata, and what a conversation requires
Authors: Green Mitchell S.
Published: January 2011

An approach is provided to the prediction and explanation of quantity implicata (implicata whose calculation depends on adversion to Grice's maxim of Quantity) that, unlike the majority of approaches available, does not construe Quantity as requiring speakers to make the strongest claim that their evidence permits. Central to this treatment is an elaboration of the notion of what a conversation requires as appealed to in the Cooperative Principle and the Quantity maxim. What a conversation requires is construed as depending, at any given point, upon (i) the aim(s) of the conversation taking place, (ii) the conversational record, which includes such features as common ground and salience relations among objects, and (iii) any proffered illocution calling for a reply. In accounting for this third dimension a partial characterization is provided of the speech acts of assertion and interrogation in terms of their role in constraining the progress of the conversation in which they occur.
A metacognitive model of conversational planning
Authors: Hayashi Takuo
Published: January 2011

The present study discusses the mechanism and formalism of conversational planning. It is argued that the planner engages in a variety of metacognition as s/he perceives, interprets, evaluates, and produces cognitive actions that require careful attention and analysis. Following Flavell's (1981) model of cognitive monitoring, a metacognitive model of conversational planning is proposed. The model consists of several cognitive and metacognitive components that are grouped into three categories: Causal Knowledge, Working Knowledge, and Conscious Experiences. Next, to elaborate the metacognitive components of the model, several examples of metacognitive variables in problem-solving situations are proposed. Then, focusing on these variables, the proposed model of conversational planning is illustrated using natural data taken from a clinical supervision session. In the last section, the relevance of the present study to pragmatics is briefly discussed with respect to mental operations involved in interpretation.
Interdisciplinary Research—Difficulties and Benefits
Authors: Kurz Ingrid
Published: January 2011

Part One outlines the desirability and difficulties of an interdisciplinary approach to interpretation research and theory. Part Two describes the design, implementation and first results of a collaborative study: EEG recordings during mental simultaneous interpretation into L1 and L2 were compared with EEG recordings during other cognitive tasks (shadowing, mental arithmetic, listening to music) and with the EEG at rest to investigate the cortical processes during simultaneous interpretation. Both hemispheres are involved in simultaneous interpretation, most of all the temporal regions (left more than right), and there are EEG differences between tasks involving verbal thinking and non-verbal tasks and between simultaneous interpretation into L1 and L2.
Su(dx) E3 ubiquitin ligase–dependent and –independent functions of Polychaetoid, the Drosophila ZO-1 homologue
Authors: Djiane Alexandre , Shimizu Hideyuki , Wilkin Marian , Mazleyrat Sabine , Jennings Martin D. , Avis Johanna , Bray Sarah , Baron Martin
Published: January 2011

Zona occludens (ZO) proteins are molecular scaffolds localized to cell junctions, which regulate epithelial integrity in mammals. Using newly generated null alleles, we demonstrate that polychaetoid (pyd), the unique Drosophila melanogaster ZO homologue, regulates accumulation of adherens junction–localized receptors, such as Notch, although it is dispensable for epithelial polarization. Pyd positively regulates Notch signaling during sensory organ development but acts negatively on Notch to restrict the ovary germline stem cell niche. In both contexts, we identify a core antagonistic interaction between Pyd and the WW domain E3 ubiquitin ligase Su(dx). Pyd binds Su(dx) directly, in part through a noncanonical WW-binding motif. Pyd also restricts epithelial wing cell numbers to control adult wing shape, a function associated with the FERM protein Expanded and independent of Su(dx). As both Su(dx) and Expanded regulate trafficking, we propose that a conserved role of ZO proteins is to coordinate receptor trafficking and signaling with junctional organization.
A novel fast mechanism for GPCR-mediated signal transduction—control of neurotransmitter release
Authors: Kupchik Yonatan M. , Barchad-Avitzur Ofra , Wess Jürgen , Ben-Chaim Yair , Parnas Itzchak , Parnas Hanna
Published: January 2011

Reliable neuronal communication depends on accurate temporal correlation between the action potential and neurotransmitter release. Although a requirement for Ca2+ in neurotransmitter release is amply documented, recent studies have shown that voltage-sensitive G protein–coupled receptors (GPCRs) are also involved in this process. However, how slow-acting GPCRs control fast neurotransmitter release is an unsolved question. Here we examine whether the recently discovered fast depolarization-induced charge movement in the M2-muscarinic receptor (M2R) is responsible for M2R-mediated control of acetylcholine release. We show that inhibition of the M2R charge movement in Xenopus oocytes correlated well with inhibition of acetylcholine release at the mouse neuromuscular junction. Our results suggest that, in addition to Ca2+ influx, charge movement in GPCRs is also necessary for release control.
Heparan sulfate proteoglycan syndecan-3 is a novel receptor for GDNF, neurturin, and artemin
Authors: Bespalov Maxim M. , Sidorova Yulia A. , Tumova Sarka , Ahonen-Bishopp Anni , Magalhães Ana Cathia , Kulesskiy Evgeny , Paveliev Mikhail , Rivera Claudio , Rauvala Heikki , Saarma Mart
Published: January 2011

Glial cell line–derived neurotrophic factor (GDNF) family ligands (GFLs) are potent survival factors for dopaminergic neurons and motoneurons with therapeutic potential for Parkinson’s disease. Soluble GFLs bind to a ligand-specific glycosylphosphatidylinositol-anchored coreceptor (GDNF family receptor α) and signal through the receptor tyrosine kinase RET. In this paper, we show that all immobilized matrix-bound GFLs, except persephin, use a fundamentally different receptor. They interact with syndecan-3, a transmembrane heparan sulfate (HS) proteoglycan, by binding to its HS chains with high affinity. GFL–syndecan-3 interaction mediates both cell spreading and neurite outgrowth with the involvement of Src kinase activation. GDNF promotes migration of cortical neurons in a syndecan-3–dependent manner, and in agreement, mice lacking syndecan-3 or GDNF have a reduced number of cortical γ-aminobutyric acid–releasing neurons, suggesting a central role for the two molecules in cortical development. Collectively, syndecan-3 may directly transduce GFL signals or serve as a coreceptor, presenting GFLs to the signaling receptor RET.
Strain-specific activation of the NF-κB pathway by GRA15, a novel Toxoplasma gondii dense granule protein
Authors: Rosowski Emily E. , Lu Diana , Julien Lindsay , Rodda Lauren , Gaiser Rogier A. , Jensen Kirk D.C. , Saeij Jeroen P.J.
Published: January 2011

NF-κB is an integral component of the immune response to Toxoplasma gondii. Although evidence exists that T. gondii can directly modulate the NF-κB pathway, the parasite-derived effectors involved are unknown. We determined that type II strains of T. gondii activate more NF-κB than type I or type III strains, and using forward genetics we found that this difference is a result of the polymorphic protein GRA15, a novel dense granule protein which T. gondii secretes into the host cell upon invasion. A GRA15-deficient type II strain has a severe defect in both NF-κB nuclear translocation and NF-κB–mediated transcription. Furthermore, human cells expressing type II GRA15 also activate NF-κB, demonstrating that GRA15 alone is sufficient for NF-κB activation. Along with the rhoptry protein ROP16, GRA15 is responsible for a large part of the strain differences in the induction of IL-12 secretion by infected mouse macrophages. In vivo bioluminescent imaging showed that a GRA15-deficient type II strain grows faster compared with wild-type, most likely through its reduced induction of IFN-γ. These results show for the first time that a dense granule protein can modulate host signaling pathways, and dense granule proteins can therefore join rhoptry proteins in T. gondii’s host cell–modifying arsenal.
A highly tilted binding mode by a self-reactive T cell receptor results in altered engagement of peptide and MHC
Authors: Sethi Dhruv K. , Schubert David A. , Anders Anne-Kathrin , Heroux Annie , Bonsor Daniel A. , Thomas Chantz P. , Sundberg Eric J. , Pyrdol Jason , Wucherpfennig Kai W.
Published: January 2011

Self-reactive T cells that escape elimination in the thymus can cause autoimmune pathology, and it is therefore important to understand the structural mechanisms of self-antigen recognition. We report the crystal structure of a T cell receptor (TCR) from a patient with relapsing-remitting multiple sclerosis that engages its self-peptide–major histocompatibility complex (pMHC) ligand in an unusual manner. The TCR is bound in a highly tilted orientation that prevents interaction of the TCR-α chain with the MHC class II β chain helix. In this structure, only a single germline-encoded TCR loop engages the MHC protein, whereas in most other TCR-pMHC structures all four germline-encoded TCR loops bind to the MHC helices. The tilted binding mode also prevents peptide contacts by the short complementarity-determining region (CDR) 3β loop, and interactions that contribute to peptide side chain specificity are focused on the CDR3α loop. This structure is the first example in which only a single germline-encoded TCR loop contacts the MHC helices. Furthermore, the reduced interaction surface with the peptide may facilitate TCR cross-reactivity. The structural alterations in the trimolecular complex are distinct from previously characterized self-reactive TCRs, indicating that there are multiple unusual ways for self-reactive TCRs to bind their pMHC ligand.
Weighted Sobolev inequalities under lower Ricci curvature bounds
Authors: Hein Hans-Joachim
Published: January 2011

We obtain sharp weighted Poincaré and Sobolev inequalities over complete, noncompact Riemannian manifolds with polynomial volume growth and a quadratically decaying lower bound on Ricci. This improves and extends earlier work of Tian-Yau and Minerbe. We deduce a sharp existence result for bounded solutions of the Poisson equation on such manifolds, highlighting the well-known distinction between spaces of volume growth≤2\leq 2and>2> 2in terms of their Green’s functions. We also show that if the manifold is nonparabolic and carries a smooth function which behaves like the radius function of a cone, then these solutions almost decay at the rates expected from a cone.
Slippage in Conservation Cost Sharing
Authors: Lichtenberg Erik , Smith-Ramírez Ricardo
Published: January 2011

We examine whether subsidies for conservation on working farmland induce farmers to expand cultivation on more vulnerable land, potentially offsetting reductions in environmental spillovers, using a switching regression model with endogenous switching and censored endogenous variables applied to Maryland farm‐level data. We find no indication that cost share awards are targeted toward water quality improvements. Receipt of cost sharing increases conservation practice adoption but not the shares of land allocated to conservation, implying little adverse selection in awards. Cost sharing decreases the share of land allocated to vegetative cover, so that environmental quality improvements from conservation are likely offset to some degree.
The Measurement of Cross-cutting Cleavages and Other Multidimensional Cleavage Structures
Authors: Selway Joel Sawat
Published: January 2011

Many studies in economics and political science include the concept of ethnic diversity as a key independent variable in empirical studies. To date, however, only single-dimensional measures of ethnic diversity, such as ethnic fractionalization, have been available. In this paper, I define and measure three multidimensional characteristics of social structure—cross-cuttingness, cross-fractionalization, and subgroup fractionalization—and present a new cross-national data set comprised of indices along combinations of five cleavages: race, language, religion, region, and income. After addressing important definitional and measurement issues, I discuss the data and show how their inclusion in economic growth regressions reopens the theoretical debate regarding the influence of ethnic diversity, indicating the potential for these new indices to shed light on the role of ethnic diversity (and social structure more generally) with regards to a number of phenomena of concern to political scientists. The data set is publicly available from the Inter-University Consortium for Political and Social Research data archives and the Institute for Quantitative Social Science Dataverse Network.
Rectal Biopsies Obtained With Jumbo Biopsy Forceps in the Evaluation of Hirschsprung Disease
Authors: Hirsch Barry Z , Angelides Anastasios G , Goode Susan P , Garb Jane L
Published: January 2011

Background and Aim:

Refractory constipation is an extremely common problem in infants and children. The diagnostic suspicion of Hirschsprung disease often arises in this clinical setting. Diagnosing Hirschsprung disease can be difficult; however, excluding the diagnosis is much easier, only requiring the demonstration of ganglion cells in the distal rectum. The most common method for obtaining tissue from the rectum involves a blind suction biopsy. This technique has been complicated by serious adverse events, equipment malfunction, and inadequate specimens. Our goal was to evaluate the adequacy of specimens obtained with a flexible endoscope and jumbo biopsy forceps to rule out Hirschsprung disease in the child outside the newborn period.

Patients and Methods:

We retrospectively reviewed 668 rectal biopsies taken during 167 endoscopies on 156 patients being evaluated for Hirschsprung disease from 2001 to 2008 at the Baystate Medical Center Children's Hospital. Four biopsies were taken from each patient approximately 2.5 cm from the anal verge. Biopsies were obtained using a flexible endoscope and jumbo biopsy forceps. During the first 6 years the Olympus FB‐50U‐1 large cup fenestrated biopsy forceps was used. During the last 2 years the Boston Scientific Radial Jaw 4 Jumbo biopsy forceps was used instead.

Results:

The Boston Scientific Radial Jaw 4 Jumbo biopsy forceps yielded adequate specimens 93% of the time, which surpassed most published results of other techniques. There were no complications reported.

Conclusions:

Obtaining rectal biopsies with a flexible endoscope and jumbo biopsy forceps is a safe and effective means to rule out the diagnosis of Hirschsprung disease in children.
Functional Characterization of Mutations in the Myosin Vb Gene Associated With Microvillus Inclusion Disease
Authors: Szperl Agata M , Golachowska Magdalena R , Bruinenberg Marcel , Prekeris Rytis , Thunnissen Andy‐Mark WH , Karrenbeld Arend , Dijkstra Gerard , Hoekstra Dick , Mercer David , Ksiazyk Janusz , Wijmenga Cisca , Wapenaar Martin C , Rings Edmond HHM , van IJzendoorn Sven CD
Published: January 2011

Objectives:

Microvillus inclusion disease (MVID) is a rare autosomal recessive enteropathy characterized by intractable diarrhea and malabsorption. Recently, various MYO5B gene mutations have been identified in patients with MVID. Interestingly, several patients with MVID showed only a MYO5B mutation in 1 allele (heterozygous) or no mutations in the MYO5B gene, illustrating the need to further functionally characterize the cell biological effects of the MYO5B mutations.

Patients and Methods:

The genomic DNA of 9 patients diagnosed as having MVID was screened for MYO5B mutations, and quantitative polymerase chain reaction and immunohistochemistry on the material of 2 patients was performed to investigate resultant cellular consequences.

Results:

We demonstrate for the first time that MYO5B mutations can be correlated with altered myosin Vb messenger RNA expression and with an aberrant subcellular distribution of the myosin Vb protein. Moreover, we demonstrate that the typical and myosin Vb–controlled accumulation of Rab11a‐ and FIP5‐positive recycling endosomes in the apical cytoplasm of the cells is abolished in MVID enterocytes, which is indicative of altered myosin Vb function. Moreover, we report 8 novel MYO5B mutations in 9 patients of various ethnic backgrounds with MVID, including compound heterozygous mutations.

Conclusions:

Our functional analysis indicates that MYO5B mutations can be correlated with an aberrant subcellular distribution of the myosin Vb protein, and apical recycling endosomes, which, together with the additional compound heterozygous mutations, significantly strengthen the link between MYO5B and MVID.
Esophageal Subepithelial Fibrosis and Hyalinization Are Features of Eosinophilic Esophagitis
Authors: Li‐Kim‐Moy Jean P , Tobias Vivienne , Day Andrew S , Leach Steven , Lemberg Daniel A
Published: January 2011

Background and Objective:

Eosinophilic esophagitis (EE) is characterized by marked esophageal mucosal eosinophilia on histological examination. Although the clinical and histological features of EE are increasingly recognized, the overlap of clinical symptoms and histological findings with gastroesophageal reflux disease (GERD) can lead to diagnostic difficulty. In children with EE we sought to define the frequency of subepithelial fibrosis and define the clinical correlates of this feature. The specificity of this finding in EE was obtained by comparison with a matched group of children with GERD, to ascertain its usefulness as a histological aid in differentiating between the 2 diagnoses.

Patients and Methods:

Comparison was made between 27 patients with EE and 24 patients with GERD, whose endoscopic biopsy specimens included subepithelial tissue. Demographic data, symptoms, endoscopic findings, and other histological findings were also compared.

Results:

In contrast to patients with GERD, those with EE more commonly reported longer periods of symptoms (especially dysphagia) and were more likely to have endoscopic abnormalities. Subepithelial fibrosis was present in 89% of patients with EE and 37.5% of patients with GERD (P < 0.0001). The features of fibrosis in EE included uniformity and hyalinization, whereas the fibrosis in GERD was predominantly associated with lymphoid tissue.

Conclusions:

Subepithelial fibrosis commonly occurs in children with EE and is associated with increased age and length of symptoms. We propose that along with mucosal eosinophilic infiltration the presence of subepithelial fibrosis is a feature of EE.
Association of Mycobacterium avium subspecies paratuberculosis With Crohn Disease in Pediatric Patients
Authors: Lee Adrienne , Griffiths Tanya A , Parab Rohan S , King Robin K , Dubinsky Marla C , Urbanski Stefan J , Wrobel Iwona , Rioux Kevin P
Published: January 2011

Objectives:

The aim of the present study was to determine the prevalence of Mycobacterium avium subsp paratuberculosis (MAP) DNA in intestinal biopsies from pediatric patients with granulomatous Crohn disease (CD) or ulcerative colitis (UC), and matched control subjects without inflammatory bowel disease (IBD).

Patients and Methods:

DNA was extracted from formalin‐fixed paraffin‐embedded colonic and ileal biopsies from patients with CD (n = 22) or UC (n = 20), and from controls without IBD (n = 21). IS900 nested polymerase chain reaction was performed in triplicate to determine the presence of MAP‐specific DNA.

Results:

In mucosal biopsies from terminal ileum, IS900 amplicons were detected in 1 of 19 (5.2%) control subjects, 1 of 20 (5%) patients with UC, and 7 of 20 (35%) patients with CD (P < 0.05 vs controls, odds ratio 9.6). In colonic biopsies, IS900 amplicons were detected in 0 of 19 control subjects, 1 of 19 (5.2%) patients with UC, and 5 of 19 (26.3%) patients with CD (P < 0.05 vs controls, odds ratio 14.8). In patients with CD, there was no correlation between disease activity and the presence of IS900.

Conclusions:

Our technique enabled sensitive and specific detection of MAP DNA in archival endoscopic biopsy specimens. Although MAP‐specific DNA can be detected in about 5% of intestinal biopsies from children with UC or controls without IBD, its presence was significantly associated with pediatric granulomatous CD, being particularly prevalent in ileal tissue. This easily defined clinical subset of patients may be useful for additional studies to determine the role of MAP in CD.
Functional antagonism between histone H3K4 demethylases in vivo
Authors: Di Stefano Luisa , Walker James A. , Burgio Giosalba , Corona Davide F.V. , Mulligan Peter , Näär Anders M. , Dyson Nicholas J.
Published: January 2011

Dynamic regulation of histone modifications is critical during development, and aberrant activity of chromatin-modifying enzymes has been associated with diseases such as cancer. Histone demethylases have been shown to play a key role in eukaryotic gene transcription; however, little is known about how their activities are coordinated in vivo to regulate specific biological processes. In Drosophila, two enzymes, dLsd1 (Drosophila ortholog of lysine-specific demethylase 1) and Lid (little imaginal discs), demethylate histone H3 at Lys 4 (H3K4), a residue whose methylation is associated with actively transcribed genes. Our studies show that compound mutation of Lid and dLsd1 results in increased H3K4 methylation levels. However, unexpectedly, Lid mutations strongly suppress dLsd1 mutant phenotypes. Investigation of the basis for this antagonism revealed that Lid opposes the functions of dLsd1 and the histone methyltransferase Su(var)3–9 in promoting heterochromatin spreading at heterochromatin–euchromatin boundaries. Moreover, our data reveal a novel role for dLsd1 in Notch signaling in Drosophila, and a complex network of interactions between dLsd1, Lid, and Notch signaling at euchromatic genes. These findings illustrate the complexity of functional interplay between histone demethylases in vivo, providing insights into the epigenetic regulation of heterochromatin/euchromatin boundaries by Lid and dLsd1 and showing their involvement in Notch pathway-specific control of gene expression in euchromatin.
Initial transcribed region sequences influence the composition and functional properties of the bacterial elongation complex
Authors: Deighan Padraig , Pukhrambam Chirangini , Nickels Bryce E. , Hochschild Ann
Published: January 2011

The bacterial RNA polymerase (RNAP) holoenzyme consists of a catalytic core enzyme (α2ββ′ω) in complex with a σ factor that is essential for promoter recognition and transcription initiation. During early elongation, the stability of interactions between σ and the remainder of the transcription complex decreases. Nevertheless, there is no mechanistic requirement for release of σ upon the transition to elongation. Furthermore, σ can remain associated with RNAP during transcription elongation and influence regulatory events that occur during transcription elongation. Here we demonstrate that promoter-like DNA sequence elements within the initial transcribed region that are known to induce early elongation pausing through sequence-specific interactions with σ also function to increase the σ content of downstream elongation complexes. Our findings establish σ-dependent pausing as a mechanism by which initial transcribed region sequences can influence the composition and functional properties of the transcription elongation complex over distances of at least 700 base pairs.
Positive control of cell division: FtsZ is recruited by SsgB during sporulation ofStreptomyces
Authors: Willemse Joost , Borst Jan Willem , de Waal Ellen , Bisseling Ton , van Wezel Gilles P.
Published: January 2011

In bacteria that divide by binary fission, cell division starts with the polymerization of the tubulin homolog FtsZ at mid-cell to form a cell division scaffold (the Z ring), followed by recruitment of the other divisome components. The current view of bacterial cell division control starts from the principle of negative checkpoints that prevent incorrect Z-ring positioning. Here we provide evidence of positive control of cell division during sporulation ofStreptomyces, via the direct recruitment of FtsZ by the membrane-associated divisome component SsgB. In vitro studies demonstrated that SsgB promotes the polymerization of FtsZ. The interactions are shown in vivo by time-lapse imaging and Förster resonance energy transfer and fluorescence lifetime imaging microscopy (FRET-FLIM), and are corroborated independently via two-hybrid studies. As determined by fluorescence recovery after photobleaching (FRAP), the turnover of FtsZ protofilaments increased strongly at the time of Z-ring formation. The surprising positive control of Z-ring formation by SsgB implies the evolution of an entirely new way of Z-ring control, which may be explained by the absence of a mid-cell reference point in the long multinucleoid hyphae. In turn, the localization of SsgB is mediated through the orthologous SsgA, and premature expression of the latter is sufficient to directly activate multiple Z-ring formation and hyperdivision at early stages of theStreptomycescell cycle.
Preparation of Extracts from Yeast
Authors: Simpson Richard J.
Published: January 2011

INTRODUCTION

Because yeast is exceptionally well suited to genetic analysis, both classical and molecular, it is an attractive system for expressing recombinant animal proteins for purification purposes. Methods available for lysing yeast cells include autolysis, pressure cells (e.g., French press), abrasives (glass bead vortexing), and enzymatic lysis (e.g., zymolase). One of the simplest methods, discussed in this protocol, involves the abrasive action of well-agitated glass beads. This is a very effective method for both low volumes (e.g., <1 mL using a microcentrifuge tube) and many liters using a specialized DynoMill apparatus. Cell breakage is typically >95%, as assessed by phase-contrast microscopy.
Multicolor Brainbow Imaging in Zebrafish
Authors: Pan Y. Albert , Livet Jean , Sanes Joshua R. , Lichtman Jeff W. , Schier Alexander F.
Published: January 2011

INTRODUCTION

This protocol describes how to use the Brainbow strategy to label neurons in many different hues. The Brainbow system uses a random Cre/lox recombination to create varied combinations of red, blue, and green fluorescent proteins in each cell. The differences in color allow users to follow multiple cells, regardless of how closely they are positioned. This protocol describes how to use Brainbow imaging in zebrafish and provides examples of how to use color as a guide to trace axonal processes. We use the zebrafish trigeminal sensory ganglion as an example and discuss potential modifications for the general use of this technique.
Labeling Tetracysteine-Tagged Proteins with Biarsenical Dyes for Live Cell Imaging
Authors: Gaietta Guido M. , Deerinck Thomas J. , Ellisman Mark H.
Published: January 2011

INTRODUCTION

Correlation of real-time or time-lapse light microscopy (LM) with electron microscopy (EM) of cells can be performed with biarsenical dyes. These dyes fluorescently label tetracysteine-tagged proteins so that they can be imaged with LM and, upon fluorescent photoconversion of 3,3′-diaminobenzidine tetrahydrochloride (DAB), with EM as well. In the following protocol, cells expressing tetracysteine-tagged proteins are labeled for 1 h with biarsenical dyes. The volumes indicated are for a single 30-mm culture dish containing 2 mL of labeling medium. Scale the suggested volumes up or down depending upon the size of the culture dish used in the labeling. The same procedure can be adapted for longer labeling times by lowering the amount of dye used to 50-100 nM; however, the amount of the competing dithiol EDT is maintained at 10-20 μM. Longer labeling times often produce higher signal-to-noise ratios and cause less trauma to the treated cells prior to imaging.
Fluorescence Photoconversion of Biarsenical-Labeled Cells for Correlated Electron Microscopy (EM)
Authors: Gaietta Guido M. , Deerinck Thomas J. , Ellisman Mark H.
Published: January 2011

INTRODUCTION

Correlated light microscopy (LM)/electron microscopy (EM) analysis can be achieved by using biarsenical dyes to fluorescently label tetracysteine-tagged proteins. Once live cell imaging using LM is complete, cellular activity can be halted promptly using a glutaraldehyde-based fixative. Rapid fixation preserves cellular ultrastructure and limits diffusion of reaction products. This protocol provides details on rapid fixation of cells, followed by fluorescence photoconversion of 3,3′-diaminobenzidine tetrahydrochloride (DAB) and sample processing for EM that can be correlated with the live cell LM images.
Preparation of Dissociated Ommatidia from Drosophila
Authors: Dolph Patrick , Nair Amit , Raghu Padinjat
Published: January 2011

INTRODUCTION

Adult Drosophila have a compound eye composed of approximately 750 repeating units, called ommatidia, packed together to form the retina. Each ommatidium is a precise arrangement of 19 cells: eight photoreceptors (primary sensory neurons) and 11 accessory cells. Analysis of visual physiology in Drosophila photoreceptors has been central to understanding a number of important areas of modern biology, including the G-protein-coupled receptor cycle, phosphoinositide signaling, and calcium signaling. Analysis of photoreceptor performance and synaptic transmission are areas of neurobiology that have been studied using Drosophila photoreceptors as a model system. Electrophysiological analysis of responses to light is a powerful tool for characterizing and understanding visual transduction in Drosophila photoreceptors. This protocol describes the isolation of dissociated ommatidia for use in voltage-clamp recordings of currents from photoreceptors, allowing detailed analysis of ion channels such as the transient receptor potential and potassium channels in photoreceptors. Mechanical dissociation of ommatidia is typically performed in flies that are <4 h post-eclosion. In animals older than this, the ommatidia become progressively more firmly attached to each other and cannot be dissociated mechanically without causing substantial damage to the constituent photoreceptors. Like the rest of the fly, the eye is surrounded by a cuticle. Thus, before the dissociation process, the eye is dissected from the rest of the head and the retina is scooped out of the cuticular covering.