Recent research suggests that increased left hemisphere cortical activity, primarily of the left frontal cortex, is associated with improved naming performance in stroke patients with aphasia. Our ...aim was to determine whether anodal transcranial direct-current stimulation (tDCS), a method thought to increase cortical excitability, would improve naming accuracy in stroke patients with aphasia when applied to the scalp overlying the left frontal cortex.
Ten patients with chronic stroke-induced aphasia received 5 days of anodal tDCS (1 mA for 20 minutes) and 5 days of sham tDCS (for 20 minutes, order randomized) while performing a computerized anomia treatment. tDCS positioning was guided by a priori functional magnetic resonance imaging results for each individual during an overt naming task to ensure that the active electrode was placed over structurally intact cortex.
Results revealed significantly improved naming accuracy of treated items (F1,9=5.72, P<0.040) after anodal tDCS compared with sham tDCS. Patients who demonstrated the most improvement were those with perilesional areas closest to the stimulation site. Crucially, this treatment effect persisted at least 1 week after treatment.
Our findings suggest that anodal tDCS over the left frontal cortex can lead to enhanced naming accuracy in stroke patients with aphasia and, if proved to be effective in larger studies, may provide a supplementary treatment approach for anomia.
Trimethylation of histone H3 at lysine 4 (H3K4me3) is a chromatin modification known to mark the transcription start sites of active genes. Here, we show that H3K4me3 domains that spread more broadly ...over genes in a given cell type preferentially mark genes that are essential for the identity and function of that cell type. Using the broadest H3K4me3 domains as a discovery tool in neural progenitor cells, we identify novel regulators of these cells. Machine learning models reveal that the broadest H3K4me3 domains represent a distinct entity, characterized by increased marks of elongation. The broadest H3K4me3 domains also have more paused polymerase at their promoters, suggesting a unique transcriptional output. Indeed, genes marked by the broadest H3K4me3 domains exhibit enhanced transcriptional consistency rather than increased transcriptional levels, and perturbation of H3K4me3 breadth leads to changes in transcriptional consistency. Thus, H3K4me3 breadth contains information that could ensure transcriptional precision at key cell identity/function genes.
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•Broad H3K4me3 domains mark cell identity genes and can be used as a discovery tool•Broad H3K4me3 domains are a distinct entity defined by specific Pol II regulation•Genes marked by broad H3K4me3 domains have increased transcriptional consistency•Perturbation of H3K4me3 breadth leads to changes in transcriptional consistency
Genes marked by broad H3K4me3 domains have increased transcriptional consistency.
Only a very small fraction of long noncoding RNAs (lncRNAs) are well characterized. The evolutionary history of lncRNAs can provide insights into their functionality, but the absence of lncRNA ...annotations in non-model organisms has precluded comparative analyses. Here we present a large-scale evolutionary study of lncRNA repertoires and expression patterns, in 11 tetrapod species. We identify approximately 11,000 primate-specific lncRNAs and 2,500 highly conserved lncRNAs, including approximately 400 genes that are likely to have originated more than 300 million years ago. We find that lncRNAs, in particular ancient ones, are in general actively regulated and may function predominantly in embryonic development. Most lncRNAs evolve rapidly in terms of sequence and expression levels, but tissue specificities are often conserved. We compared expression patterns of homologous lncRNA and protein-coding families across tetrapods to reconstruct an evolutionarily conserved co-expression network. This network suggests potential functions for lncRNAs in fundamental processes such as spermatogenesis and synaptic transmission, but also in more specific mechanisms such as placenta development through microRNA production.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, KISLJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
While most cells maintain a diploid state, polyploid cells exist in many organisms and are particularly prevalent within the mammalian placenta 1, where they can generate more than 900 copies of the ...genome 2. Polyploidy is thought to be an efficient method of increasing the content of the genome by avoiding the costly and slow process of cytokinesis 1, 3, 4. Polyploidy can also affect gene regulation by amplifying a subset of genomic regions required for specific cellular function 1, 3, 4. This mechanism is found in the fruit fly Drosophila melanogaster, where polyploid ovarian follicle cells amplify genomic regions containing chorion genes, which facilitate secretion of eggshell proteins 5. Here, we report that genomic amplification also occurs in mammals at selective regions of the genome in parietal trophoblast giant cells (p-TGCs) of the mouse placenta. Using whole-genome sequencing (WGS) and digital droplet PCR (ddPCR) of mouse p-TGCs, we identified five amplified regions, each containing a gene family known to be involved in mammalian placentation: the prolactins (two clusters), serpins, cathepsins, and the natural killer (NK)/C-type lectin (CLEC) complex 6–12. We report here the first description of amplification at selective genomic regions in mammals and present evidence that this is an important mode of genome regulation in placental TGCs.
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•Trophoblast giant cells amplify genomic regions containing placental genes•Prolactins, serpins, cathepsins, and the NK/CLEC complex are amplified•Genes contained within the amplified clusters are highly expressed•Amplification occurs during endoreplication, independent of replication timing
Hannibal and Baker provide the first description of amplification at selective genomic regions in mammals and present evidence that this is an important mode of genome regulation in polyploid placental trophoblast giant cells.
Previous evidence suggests that anodal transcranial direct current stimulation (A-tDCS) applied to the left hemisphere can improve aphasic participants' ability to name common objects. The current ...study further examined this issue in a more tightly controlled experiment in participants with fluent aphasia.
We examined the effect of A-tDCS on reaction time during overt picture naming in 8 chronic stroke participants. Anode electrode placement targeted perilesional brain regions that showed the greatest activation on a pretreatment functional MRI scan administered during overt picture naming with the reference cathode electrode placed on the contralateral forehead. A-tDCS (1 mA; 20-minute) was compared with sham tDCS (S-tDCS) in a crossover design. Participants received 10 sessions of computerized anomia treatment; 5 sessions included A-tDCS and 5 included S-tDCS.
Coupling A-tDCS with behavioral language treatment reduced reaction time during naming of trained items immediately posttreatment (Z=1.96, P=0.025) and at subsequent testing 3 weeks later (Z=2.52, P=0.006).
A-tDCS administered during language treatment decreased processing time during picture naming by fluent aphasic participants. Additional studies combining A-tDCS, an inexpensive method with no reported serious side effects, with behavioral language therapy are recommended.
While a few researchers have started to chip away at the notion that retail density is always negative, extant studies do not empirically address the question of why some shoppers respond negatively ...to a specific level of density while others respond positively. We examine this issue by drawing upon field theory (Lewin
1939
) to shed light on how shoppers vary in terms of deeper motives (McClelland
1953
) to seek control or intimacy with others in retail mall settings, and whether these motives influence shopping orientations. Shopping orientation is then hypothesized to affect perceptions of crowding, and, in turn, subsequent affective responses to the mall shopping experience. Moreover, we examine whether individual differences (gender and age) can help retailers segment those with different shopping orientations and the motives that influence these orientations. We found that task and social shopping orientations were influenced by deeper motives for control and intimacy. The causal relationships between shopping motive, shopping orientation, and consumers’ affective responses of stress and excitement were also discovered. Finally, we address theoretical and managerial implications of our results.
Although numerous published reports have demonstrated the beneficial effects of transcranial direct-current stimulation (tDCS) on task performance, fundamental questions remain regarding the optimal ...electrode configuration on the scalp. Moreover, it is expected that lesioned brain tissue will influence current flow and should therefore be considered (and perhaps leveraged) in the design of individualized tDCS therapies for stroke. The current report demonstrates how different electrode configurations influence the flow of electrical current through brain tissue in a patient who responded positively to a tDCS treatment targeting aphasia. The patient, a 60-year-old man, sustained a left hemisphere ischemic stroke (lesion size = 87.42 mL) 64 months before his participation. In this study, we present results from the first high-resolution (1 mm3 ) model of tDCS in a brain with considerable stroke-related damage; the model was individualized for the patient who received anodal tDCS to his left frontal cortex with the reference cathode electrode placed on his right shoulder. We modeled the resulting brain current flow and also considered three additional reference electrode positions: right mastoid, right orbitofrontal cortex, and a “mirror” configuration with the anode over the undamaged right cortex. Our results demonstrate the profound effect of lesioned tissue on resulting current flow and the ability to modulate current pattern through the brain, including perilesional regions, through electrode montage design. The complexity of brain current flow modulation by detailed normal and pathologic anatomy suggest: (1) That computational models are critical for the rational interpretation and design of individualized tDCS stroke-therapy; and (2) These models must accurately reproduce head anatomy as shown here.
The mammalian placenta is remarkably distinct between species, suggesting a history of rapid evolutionary diversification. To gain insight into the molecular drivers of placental evolution, we ...compared biochemically predicted enhancers in mouse and rat trophoblast stem cells (TSCs) and found that species-specific enhancers are highly enriched for endogenous retroviruses (ERVs) on a genome-wide level. One of these ERV families, RLTR13D5, contributes hundreds of mouse-specific histone H3 lysine 4 monomethylation (H3K4me1)- and histone H3 lysine 27 acetylation (H3K27ac)-defined enhancers that functionally bind Cdx2, Eomes and Elf5-core factors that define the TSC regulatory network. Furthermore, we show that RLTR13D5 is capable of driving gene expression in rat placental cells. Analysis in other tissues shows that species-specific ERV enhancer activity is generally restricted to hypomethylated tissues, suggesting that tissues permissive for ERV activity gain access to an otherwise silenced source of regulatory variation. Overall, our results implicate ERV enhancer co-option as a mechanism underlying the extensive evolutionary diversification of placental development.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Discovery of lineage-specific somatic copy number variation (CNV) in mammals has led to debate over whether CNVs are mutations that propagate disease or whether they are a normal, and even essential, ...aspect of cell biology. We show that 1,000 N polyploid trophoblast giant cells (TGCs) of the mouse placenta contain 47 regions, totaling 138 Megabases, where genomic copies are underrepresented (UR). UR domains originate from a subset of late-replicating heterochromatic regions containing gene deserts and genes involved in cell adhesion and neurogenesis. While lineage-specific CNVs have been identified in mammalian cells, classically in the immune system where V(D)J recombination occurs, we demonstrate that CNVs form during gestation in the placenta by an underreplication mechanism, not by recombination nor deletion. Our results reveal that large scale CNVs are a normal feature of the mammalian placental genome, which are regulated systematically during embryogenesis and are propagated by a mechanism of underreplication.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The invention of the placenta facilitated the evolution of mammals. How the placenta evolved from the simple structure observed in birds and reptiles into the complex organ that sustains human life ...is one of the great mysteries of evolution. By using a timecourse microarray analysis including the entire lifetime of the placenta, we uncover molecular and genomic changes that underlie placentation and find that two distinct evolutionary mechanisms were utilized during placental evolution in mice and human. Ancient genes involved in growth and metabolism were co-opted for use during early embryogenesis, likely enabling the accelerated development of extraembryonic tissues. Recently duplicated genes are utilized at later stages of placentation to meet the metabolic needs of a diverse range of pregnancy physiologies. Together, these mechanisms served to develop the specialized placenta, a novel structure that led to expansion of the eutherian mammal, including humankind.
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