bluuebunny/crossref_metadata_2025_split huggingface dataset:
Distinct perinatal features of the hyperpolarization-activated non-selective cation current Ih in the rat cortical plate
Authors: Battefeld Arne , Rocha Nino , Stadler Konstantin , Bräuer Anja U , Strauss Ulf 
Published: June 2012

Abstract

Background
During neocortical development, multiple voltage- and ligand-gated ion channels are differentially expressed in neurons thereby shaping their intrinsic electrical properties. One of these voltage-gated ion channels, the hyperpolarization-activated cyclic nucleotide-gated (HCN) channel and its current I
h, is an important regulator of neuronal excitability. Thus far, studies on an early I
h appearance in rodent neocortex are missing or conflicting. Therefore, we focused our study on perinatal neocortical I
h and its properties.

Results
In the perinatal rat neocortex we observed a rapid increase in the number of neurons exhibiting I
h. Perinatal I
h had unique properties: first, a pronounced cAMP sensitivity resulting in a marked shift of the voltage sufficient for half-maximum activation of the current towards depolarized voltages and second, an up to 10 times slower deactivation at physiological membrane potentials when compared to the one at postnatal day 30. The combination of these features was sufficient to suppress membrane resonance in our in silico and in vitro experiments. Although all four HCN subunits were present on the mRNA level we only detected HCN4, HCN3 and HCN1 on the protein level at P0. HCN1 protein at P0, however, appeared incompletely processed. At P30 glycosilated HCN1 and HCN2 dominated. By in silico simulations and heterologous co-expression experiments of a ‘slow’ and a ‘fast’ I
h conducting HCN channel subunit in HEK293 cells, we mimicked most characteristics of the native current, pointing to a functional combination of subunit homo- or heteromeres.

Conclusion
Taken together, these data indicate a HCN subunit shift initiated in the first 24 hours after birth and implicate a prominent perinatal role of the phylogenetically older HCN3 and/or HCN4 subunits in the developing neocortex.
Combinatorial network of transcriptional regulation and microRNA regulation in human cancer
Authors: Yu Hui , Tu Kang , Wang Yi-Jie , Mao Jun-Zhe , Xie Lu , Li Yuan-Yuan , Li Yi-Xue 
Published: June 2012

Abstract

Background
Both transcriptional control and microRNA (miRNA) control are critical regulatory mechanisms for cells to direct their destinies. At present, the combinatorial regulatory network composed of transcriptional regulations and post-transcriptional regulations is often constructed through a forward engineering strategy that is based solely on searching of transcriptional factor binding sites or miRNA seed regions in the putative target sequences. If the reverse engineering strategy is integrated with the forward engineering strategy, a more accurate and more specific combinatorial regulatory network will be obtained.

Results
In this work, utilizing both sequence-matching information and parallel expression datasets of miRNAs and mRNAs, we integrated forward engineering with reverse engineering strategies and as a result built a hypothetical combinatorial gene regulatory network in human cancer. The credibility of the regulatory relationships in the network was validated by random permutation procedures and supported by authoritative experimental evidence-based databases. The global and local architecture properties of the combinatorial regulatory network were explored, and the most important tumor-regulating miRNAs and TFs were highlighted from a topological point of view.

Conclusions
By integrating the forward engineering and reverse engineering strategies, we manage to sketch a genome-scale combinatorial gene regulatory network in human cancer, which includes transcriptional regulations and miRNA regulations, allowing systematic study of cancer gene regulation. Our work establishes a pipeline that can be extended to reveal conditional combinatorial regulatory landscapes correlating to specific cellular contexts.
New finite-size correction for local alignment score distributions
Authors: Park Yonil , Sheetlin Sergey , Ma Ning , Madden Thomas L , Spouge John L 
Published: June 2012

Abstract

Background
Local alignment programs often calculate the probability that a match occurred by chance. The calculation of this probability may require a “finite-size” correction to the lengths of the sequences, as an alignment that starts near the end of either sequence may run out of sequence before achieving a significant score.

Findings
We present an improved finite-size correction that considers the distribution of sequence lengths rather than simply the corresponding means. This approach improves sensitivity and avoids substituting an ad hoc length for short sequences that can underestimate the significance of a match. We use a test set derived from ASTRAL to show improved ROC scores, especially for shorter sequences.

Conclusions
The new finite-size correction improves the calculation of probabilities for a local alignment. It is now used in the BLAST+ package and at the NCBI BLAST web site (http://blast.ncbi.nlm.nih.gov).
C5a and its receptors in human anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis
Authors: Yuan Jun , Gou Shen-Ju , Huang Jing , Hao Jian , Chen Min , Zhao Ming-Hui 
Published: June 2012

Abstract
Introduction
The complement system is crucial for the development of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). In particular, C5a plays a central role. In this study, plasma and urinary levels of C5a as well as renal C5a receptors (CD88 and C5L2) expression were investigated in patients with AAV.

Methods
Twenty-four patients with AAV in the active phase, 19 patients with AAV in the remission phase, and 20 patients with lupus nephritis (LN) were included. Plasma and urinary levels of C5a were measured with enzyme-linked immunosorbent assay (ELISA). The staining of CD88 and C5L2 in renal specimens was detected with immunohistochemistry.

Results
The level of plasma C5a was significantly higher in patients with AAV in the active phase than that in patients in remission, that in patients with LN, and that in normal controls. The urinary C5a level was significantly higher in patients with AAV in the active phase than that in patients in remission and that in normal controls, but not significantly different between patients with active AAV and patients with LN. The mean optical density of CD88 staining in the tubulointerstitium was significantly lower in AAV patients than that in normal controls (0.0052 ± 0.0011 versus 0.029 ± 0.0042; P = 0.005). The mean optical density of C5L2 in glomeruli was significantly higher in AAV patients than that in normal controls (0.013 ± 0.0027 versus 0.0032 ± 0.0006; P < 0.001). The mean optical density of CD88 staining closely correlated with the initial eGFR (r = 0.835; P < 0.001) in AAV patients. Double-labeling immunofluorescence assay suggested that CD88 did not express on neutrophils, monocytes, or macrophages, but C5L2 expressed on neutrophils (or monocytes) and macrophages.

Conclusion
The elevated plasma and urinary C5a levels indicated complement activation in human AAV. The level of renal CD88 expression could reflect the disease severity of ANCA-associated glomerulonephritis. CD88 expression was downregulated, and C5L2 was upregulated in ANCA-associated glomerulonephritis.
The genomic landscape shaped by selection on transposable elements across 18 mouse strains
Authors: Nellåker Christoffer , Keane Thomas M , Yalcin Binnaz , Wong Kim , Agam Avigail , Belgard T Grant , Flint Jonathan , Adams David J , Frankel Wayne N , Ponting Chris P 
Published: June 2012

Abstract
Background
Transposable element (TE)-derived sequence dominates the landscape of mammalian genomes and can modulate gene function by dysregulating transcription and translation. Our current knowledge of TEs in laboratory mouse strains is limited primarily to those present in the C57BL/6J reference genome, with most mouse TEs being drawn from three distinct classes, namely short interspersed nuclear elements (SINEs), long interspersed nuclear elements (LINEs) and the endogenous retrovirus (ERV) superfamily. Despite their high prevalence, the different genomic and gene properties controlling whether TEs are preferentially purged from, or are retained by, genetic drift or positive selection in mammalian genomes remain poorly defined.

Results
Using whole genome sequencing data from 13 classical laboratory and 4 wild-derived mouse inbred strains, we developed a comprehensive catalogue of 103,798 polymorphic TE variants. We employ this extensive data set to characterize TE variants across the Mus lineage, and to infer neutral and selective processes that have acted over 2 million years. Our results indicate that the majority of TE variants are introduced though the male germline and that only a minority of TE variants exert detectable changes in gene expression. However, among genes with differential expression across the strains there are twice as many TE variants identified as being putative causal variants as expected.

Conclusions
Most TE variants that cause gene expression changes appear to be purged rapidly by purifying selection. Our findings demonstrate that past TE insertions have often been highly deleterious, and help to prioritize TE variants according to their likely contribution to gene expression or phenotype variation.
Apple miRNAs and tasiRNAs with novel regulatory networks
Authors: Xia Rui , Zhu Hong , An Yong-qiang , Beers Eric P , Liu Zongrang 
Published: June 2012

Abstract
Background
MicroRNAs (miRNAs) and their regulatory functions have been extensively characterized in model species but whether apple has evolved similar or unique regulatory features remains unknown.

Results
We performed deep small RNA-seq and identified 23 conserved, 10 less-conserved and 42 apple-specific miRNAs or families with distinct expression patterns. The identified miRNAs target 118 genes representing a wide range of enzymatic and regulatory activities. Apple also conserves two TAS gene families with similar but unique trans-acting small interfering RNA (tasiRNA) biogenesis profiles and target specificities. Importantly, we found that miR159, miR828 and miR858 can collectively target up to 81 MYB genes potentially involved in diverse aspects of plant growth and development. These miRNA target sites are differentially conserved among MYBs, which is largely influenced by the location and conservation of the encoded amino acid residues in MYB factors. Finally, we found that 10 of the 19 miR828-targeted MYBs undergo small interfering RNA (siRNA) biogenesis at the 3' cleaved, highly divergent transcript regions, generating over 100 sequence-distinct siRNAs that potentially target over 70 diverse genes as confirmed by degradome analysis.

Conclusions
Our work identified and characterized apple miRNAs, their expression patterns, targets and regulatory functions. We also discovered that three miRNAs and the ensuing siRNAs exploit both conserved and divergent sequence features of MYB genes to initiate distinct regulatory networks targeting a multitude of genes inside and outside the MYB family.
Abiraterone for the Treatment of Metastatic Castrate-Resistant Prostate Cancer
Authors: Beckett Robert D , Rodeffer Kathryn M , Snodgrass Rachel 
Published: June 2012

OBJECTIVE: To review the clinical pharmacology, efficacy, and safety of abiraterone acetate for metastatic castrate-resistant prostate cancer (mCRPC) and evaluate the drug for health-system formulary inclusion. DATA SOURCES: Literature was identified through a search of MEDLINE (1977-February 2012) and International Pharmaceutical Abstracts(1977-February 2012) using the search term abiraterone. References of identified articles were reviewed. STUDY SELECTION AND DATA EXTRACTION: All clinical trials published in English were evaluated. Studies conducted in the setting of mCRPC were included in the literature review. DATA SYNTHESIS: Despite benefits from androgen deprivation for the treatment of prostate cancer, most patients experience disease progression within 12-48 months, a phase described as castrate resistant. Abiraterone is the only Food and Drug Administration–approved hormonal treatment option for mCRPC in men who have received docetaxel and is recommended as a second-line agent for this indication in the National Comprehensive Cancer Network prostate cancer guidelines. One Phase 3 study, 2 Phase 2 studies, and 2 Phase 1 studies conducted in the setting of second-line treatment of mCRPC were identified. Treatment with abiraterone was associated with at least a 50% reduction in prostate-specific antigen (PSA) in 38-51% of patients; PSA progression ranged from 5.6-10.2 months. The only study assessing mortality outcomes found a 13% absolute reduction in mortality (ie, 42% vs 55%; HR 0.65; 95% CI 0.54 to 0.77), relative to placebo, over a median 12.8 months of follow-up. Abiraterone has been compared only to placebo, not to existing treatment options. CONCLUSIONS: Abiraterone provides a moderate improvement in disease progression and mortality in a patient population with limited treatment options. It is recommended to add this medication to outpatient formularies restricted to second-line treatment of mCRPC.
Effects of Presentation Mode on Veridical and False Memory in Individuals with Intellectual Disability
Authors: Carlin Michael , Toglia Michael P. , Belmonte Colleen , DiMeglio Chiara 
Published: June 2012

AbstractIn the present study the effects of visual, auditory, and audio–visual presentation formats on memory for thematically constructed lists were assessed in individuals with intellectual disability and mental age–matched children. The auditory recognition test included target items, unrelated foils, and two types of semantic lures: critical related foils and related foils. The audio–visual format led to better recognition of old items and lower false-alarm rates for all foil types. Those with intellectual disability had higher false-alarm rates for all foil types and experienced particular difficulty discriminating presented items from those most strongly activated internally during acquisition (i.e., critical foils). Results are consistent with the activation-monitoring framework and fuzzy-trace theory and inform best practices for designing visual supports to maximize performance in educational and work environments.
Stress, Locus of Control, and Family Cohesion and Adaptability in Parents of Children with Down, Williams, Fragile X, and Prader-Willi Syndromes
Authors: Lanfranchi Silvia , Vianello Renzo 
Published: June 2012

AbstractThe present study analyzes differences in parental stress in families of children with Down, Williams, Fragile X, and Prader-Willi syndromes, exploring factors that influence parental stress, such as child's characteristics, parental locus of control, and family cohesion and adaptability. Differences between mothers and fathers are also investigated. Parents were given self-report questionnaires to assess family stress, parental locus of control, and family cohesion and adaptability. Results showed that stress levels were lower in families of children with Down syndrome and higher in those of children with Prader-Willi syndrome. Children's characteristics and their parents' locus of control were found to be related to family stress levels in all four syndromes, but several aspects specific to a given syndrome also came to light, as well as some shared and some gender-specific features relating to mothers and fathers.
Evidence for Reciprocal Interaction Effects Among Adults with Self-Injury and Their Caregivers
Authors: Wolff Jason J. , Clary Jamie , Harper Vickie N. , Bodfish James W. , Symons Frank J. 
Published: June 2012

Abstract
Patterns of caregiver responses to client adaptive behavior were compared between adults with intellectual disabilities with and without self-injurious behavior. Participants with moderate to profound intellectual disability and self-injury (n  =  89) and age/IQ matched control participants (n  =  20) were selected from a large sample of adults living in a regional residential center. Approximately 45 minutes of direct observation data were collected for each participant during unstructured leisure time. Data were sequentially analyzed and Yule's Q scores derived and compared among groups. Results indicated that caregivers were more responsive to prosocial initiations and adaptive engagement among individuals with severe self-injurious behavior than to those with mild or no self-injurious behavior and that these responses were more likely to be in the form of a demand.
A Qualitative Analysis of General Receptive Vocabulary of Adolescents with Down Syndrome
Authors: Facon Bruno , Nuchadee Marie-Laure , Bollengier Thérèse 
Published: June 2012

Abstract
This study aimed to discover whether general receptive vocabulary is qualitatively phenotypical in Down syndrome. Sixty-two participants with Down syndrome (M age  =  16.74 years, SD  =  3.28) were individually matched on general vocabulary raw total score with 62 participants with intellectual disability of undifferentiated etiology (M age  =  16.20 years, SD  =  3.08) and 62 typical children (M age  =  5.32 years, SD  =  0.82). Item analyses using the transformed item difficulties method to detect differential item functioning across groups showed that the groups' rank orders of item difficulty were highly similar. It was concluded that the general receptive vocabulary of older children and adolescents with Down syndrome is not qualitatively distinguished when its overall size is held constant. Methodological and theoretical implications of this finding are discussed.
Extending Coalescent Theory to Autotetraploids
Authors: Arnold B , Bomblies K , Wakeley J 
Published: June 2012

Abstract
We develop coalescent models for autotetraploid species with tetrasomic inheritance. We show that the ancestral genetic process in a large population without recombination may be approximated using Kingman’s standard coalescent, with a coalescent effective population size 4N. Numerical results suggest that this approximation is accurate for population sizes on the order of hundreds of individuals. Therefore, existing coalescent simulation programs can be adapted to study population history in autotetraploids simply by interpreting the timescale in units of 4N generations. We also consider the possibility of double reduction, a phenomenon unique to polysomic inheritance, and show that its effects on gene genealogies are similar to partial self-fertilization.
Three Routes to Suppression of the Neurodegenerative Phenotypes Caused by Kinesin Heavy Chain Mutations
Authors: Djagaeva Inna , Rose Debra J , Lim Angeline , Venter Chris E , Brendza Katherine M , Moua Pangkong , Saxton William M 
Published: June 2012

Abstract
Kinesin-1 is a motor protein that moves stepwise along microtubules by employing dimerized kinesin heavy chain (Khc) subunits that alternate cycles of microtubule binding, conformational change, and ATP hydrolysis. Mutations in the Drosophila Khc gene are known to cause distal paralysis and lethality preceded by the occurrence of dystrophic axon terminals, reduced axonal transport, organelle-filled axonal swellings, and impaired action potential propagation. Mutations in the equivalent human gene, Kif5A, result in similar problems that cause hereditary spastic paraplegia (HSP) and Charcot–Marie–Tooth type 2 (CMT2) distal neuropathies. By comparing the phenotypes and the complementation behaviors of a large set of Khc missense alleles, including one that is identical to a human Kif5A HSP allele, we identified three routes to suppression of Khc phenotypes: nutrient restriction, genetic background manipulation, and a remarkable intramolecular complementation between mutations known or likely to cause reciprocal changes in the rate of microtubule-stimulated ADP release by kinesin-1. Our results reveal the value of large-scale complementation analysis for gaining insight into protein structure–function relationships in vivo and point to possible paths for suppressing symptoms of HSP and related distal neuropathies.
Activity-Dependent A-to-I RNA Editing in Rat Cortical Neurons
Authors: Sanjana Neville E , Levanon Erez Y , Hueske Emily A , Ambrose Jessica M , Li Jin Billy 
Published: June 2012

Abstract
Changes in neural activity influence synaptic plasticity/scaling, gene expression, and epigenetic modifications. We present the first evidence that short-term and persistent changes in neural activity can alter adenosine-to-inosine (A-to-I) RNA editing, a post-transcriptional site-specific modification found in several neuron-specific transcripts. In rat cortical neuron cultures, activity-dependent changes in A-to-I RNA editing in coding exons are present after 6 hr of high potassium depolarization but not after 1 hr and require calcium entry into neurons. When treatments are extended from hours to days, we observe a negative feedback phenomenon: Chronic depolarization increases editing at many sites and chronic silencing decreases editing. We present several different modulations of neural activity that change the expression of different mRNA isoforms through editing.
Patterns of Neutral Diversity Under General Models of Selective Sweeps
Authors: Coop Graham , Ralph Peter 
Published: June 2012

Abstract
Two major sources of stochasticity in the dynamics of neutral alleles result from resampling of finite populations (genetic drift) and the random genetic background of nearby selected alleles on which the neutral alleles are found (linked selection). There is now good evidence that linked selection plays an important role in shaping polymorphism levels in a number of species. One of the best-investigated models of linked selection is the recurrent full-sweep model, in which newly arisen selected alleles fix rapidly. However, the bulk of selected alleles that sweep into the population may not be destined for rapid fixation. Here we develop a general model of recurrent selective sweeps in a coalescent framework, one that generalizes the recurrent full-sweep model to the case where selected alleles do not sweep to fixation. We show that in a large population, only the initial rapid increase of a selected allele affects the genealogy at partially linked sites, which under fairly general assumptions are unaffected by the subsequent fate of the selected allele. We also apply the theory to a simple model to investigate the impact of recurrent partial sweeps on levels of neutral diversity and find that for a given reduction in diversity, the impact of recurrent partial sweeps on the frequency spectrum at neutral sites is determined primarily by the frequencies rapidly achieved by the selected alleles. Consequently, recurrent sweeps of selected alleles to low frequencies can have a profound effect on levels of diversity but can leave the frequency spectrum relatively unperturbed. In fact, the limiting coalescent model under a high rate of sweeps to low frequency is identical to the standard neutral model. The general model of selective sweeps we describe goes some way toward providing a more flexible framework to describe genomic patterns of diversity than is currently available.