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1.
Cell ; 187(14): 3741-3760.e30, 2024 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-38843831

RESUMO

Experimental studies on DNA transposable elements (TEs) have been limited in scale, leading to a lack of understanding of the factors influencing transposition activity, evolutionary dynamics, and application potential as genome engineering tools. We predicted 130 active DNA TEs from 102 metazoan genomes and evaluated their activity in human cells. We identified 40 active (integration-competent) TEs, surpassing the cumulative number (20) of TEs found previously. With this unified comparative data, we found that the Tc1/mariner superfamily exhibits elevated activity, potentially explaining their pervasive horizontal transfers. Further functional characterization of TEs revealed additional divergence in features such as insertion bias. Remarkably, in CAR-T therapy for hematological and solid tumors, Mariner2_AG (MAG), the most active DNA TE identified, largely outperformed two widely used vectors, the lentiviral vector and the TE-based vector SB100X. Overall, this study highlights the varied transposition features and evolutionary dynamics of DNA TEs and increases the TE toolbox diversity.


Assuntos
Elementos de DNA Transponíveis , Humanos , Elementos de DNA Transponíveis/genética , Engenharia Genética/métodos , Genoma Humano , Animais , Evolução Molecular
2.
Trends Genet ; 38(6): 529-553, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35307201

RESUMO

Transposable element (TE)-derived sequences are ubiquitous in most eukaryotic genomes known to date. Because their expression and mobility can lead to genomic instability, several pathways have evolved to control TEs. Nevertheless, TEs represent an important source of genomic novelty and are often co-opted for novel functions that are relevant for phenotypic divergence and adaptation. Here, we review how animals, in particular vertebrates, mitigate TE mobility and expression, alongside known examples of TE domestication. We argue that the next frontier is to understand the determinants and dynamics of TE domestication: how they shift from 'non-self' targets of epigenetic silencing to 'self' genetic elements. New technologies enable avenues of research that may close the gap between epigenetic silencing and domestication of TEs.


Assuntos
Elementos de DNA Transponíveis , Domesticação , Animais , Elementos de DNA Transponíveis/genética , Epigênese Genética/genética , Eucariotos/genética , Evolução Molecular , Vertebrados/genética
3.
Genomics ; 116(5): 110896, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39025318

RESUMO

Pamphagidae is a family of Acridoidea that inhabits the desert steppes of Eurasia and Africa. This study employed flow cytometry to estimate the genome size of eight species in the Pamphagidae. The results indicate that the genome size of the eight species ranged from 13.88 pg to 14.66 pg, with an average of 14.26 pg. This is the largest average genome size recorded for the Orthoptera families, as well as for the entire Insecta. Furthermore, the study explored the role of repetitive sequences in the genome, including their evolutionary dynamics and activity, using low-coverage next-generation sequencing data. The genome is composed of 14 different types of repetitive sequences, which collectively make up between 59.9% and 68.17% of the total genome. The Pamphagidae family displays high levels of transposable element (TE) activity, with the number of TEs increasing and accumulating since the family's emergence. The study found that the types of repetitive sequences contributing to the TE outburst events are similar across species. Additionally, the study identified unique repetitive elements for each species. The differences in repetitive sequences among the eight Pamphagidae species correspond to their phylogenetic relationships. The study sheds new light on genome gigantism in the Pamphagidae and provides insight into the correlation between genome size and repetitive sequences within the family.


Assuntos
Tamanho do Genoma , Genoma de Inseto , Animais , Elementos de DNA Transponíveis , Ortópteros/genética , Ortópteros/classificação , Sequências Repetitivas de Ácido Nucleico , Gafanhotos/genética , Gafanhotos/classificação , Evolução Molecular
4.
Plant Mol Biol ; 114(5): 108, 2024 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-39356367

RESUMO

In this paper, we have performed an in-depth study of the complete set of the satellite DNA (satDNA) families (i.e. the satellitomes) in the genome of two barley species of agronomic value in a breeding framework, H. chilense (H1 and H7 accessions) and H. vulgare (H106 accession), which can be useful tools for studying chromosome associations during meiosis. The study has led to the analysis of a total of 18 satDNA families in H. vulgare, 25 satDNA families in H. chilense (accession H1) and 27 satDNA families in H. chilense (accession H7) that constitute 46 different satDNA families forming 36 homology groups. Our study highlights different important contributions of evolutionary and applied interests. Thus, both barley species show very divergent satDNA profiles, which could be partly explained by the differential effects of domestication versus wildlife. Divergence derives from the differential amplification of different common ancestral satellites and the emergence of new satellites in H. chilense, usually from pre-existing ones but also random sequences. There are also differences between the two H. chilense accessions, which support genetically distinct groups. The fluorescence in situ hybridization (FISH) patterns of some satDNAs yield distinctive genetic markers for the identification of specific H. chilense or H. vulgare chromosomes. Some of the satellites have peculiar structures or are related to transposable elements which provide information about their origin and expansion. Among these, we discuss the existence of different (peri)centromeric satellites that supply this region with some plasticity important for centromere evolution. These peri(centromeric) satDNAs and the set of subtelomeric satDNAs (a total of 38 different families) are analyzed in the framework of breeding as the high diversity found in the subtelomeric regions might support their putative implication in chromosome recognition and pairing during meiosis, a key point in the production of addition/substitution lines and hybrids.


Assuntos
Cromossomos de Plantas , DNA Satélite , Hordeum , Hibridização in Situ Fluorescente , Hordeum/genética , DNA Satélite/genética , Cromossomos de Plantas/genética , DNA de Plantas/genética , Genoma de Planta/genética , Filogenia , Variação Genética , Meiose/genética , Evolução Molecular , Especificidade da Espécie
5.
Antimicrob Agents Chemother ; 68(4): e0152523, 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38421163

RESUMO

Monitoring antimalarial efficacy is important to detect the emergence of parasite drug resistance. Angola conducts in vivo therapeutic efficacy studies (TESs) every 2 years in its fixed sentinel sites in Benguela, Lunda Sul, and Zaire provinces. Children with uncomplicated Plasmodium falciparum malaria were treated with artemether-lumefantrine (AL), artesunate-amodiaquine (ASAQ), dihydroartemisinin-piperaquine (DP), or artesunate-pyronaridine (ASPY) and followed for 28 (AL and ASAQ) or 42 days (DP and ASPY) to assess clinical and parasitological response to treatment. Two drugs were sequentially assessed in each site in February-July 2021. The primary indicator was the Kaplan-Meier estimate of the PCR-corrected efficacy at the end of the follow-up period. A total of 622 patients were enrolled in the study and 590 (95%) participants reached a study endpoint. By day 3, ≥98% of participants were slide-negative in all study sites and arms. After PCR correction, day 28 AL efficacy was 88.0% (95% CI: 82%-95%) in Zaire and 94.7% (95% CI: 90%-99%) in Lunda Sul. For ASAQ, day 28 efficacy was 92.0% (95% CI: 87%-98%) in Zaire and 100% in Lunda Sul. Corrected day 42 efficacy was 99.6% (95% CI: 99%-100%) for ASPY and 98.3% (95% CI: 96%-100%) for DP in Benguela. High day 3 clearance rates suggest no clinical evidence of artemisinin resistance. This was the fourth of five rounds of TES in Angola showing a corrected AL efficacy <90% in a site. For Zaire, AL has had an efficacy <90% in 2013, 2015, and 2021. ASAQ, DP, and ASPY are appropriate choices as artemisinin-based combination therapies in Angola.


Assuntos
Antimaláricos , Artemisininas , Malária Falciparum , Criança , Humanos , Antimaláricos/uso terapêutico , Artesunato/uso terapêutico , Combinação Arteméter e Lumefantrina/uso terapêutico , Angola , Artemeter/uso terapêutico , Artemisininas/uso terapêutico , Amodiaquina/uso terapêutico , Malária Falciparum/tratamento farmacológico , Combinação de Medicamentos , Plasmodium falciparum
6.
J Transl Med ; 22(1): 28, 2024 01 06.
Artigo em Inglês | MEDLINE | ID: mdl-38184580

RESUMO

BACKGROUND: Electrical activity has a crucial impact on the development and survival of neurons. Numerous recent studies have shown that noninvasive electrical stimulation (NES) has neuroprotective action in various retinal disorders. OBJECTIVE: To systematically review the literature on in vivo studies and provide a comprehensive summary of the neuroprotective action and the mechanisms of NES on retinal disorders. METHODS: Based on the PRISMA guideline, a systematic review was conducted in PubMed, Web of Science, Embase, Scopus and Cochrane Library to collect all relevant in vivo studies on "the role of NES on retinal diseases" published up until September 2023. Possible biases were identified with the adopted SYRCLE's tool. RESULTS: Of the 791 initially gathered studies, 21 articles met inclusion/exclusion criteria for full-text review. The results revealed the neuroprotective effect of NES (involved whole-eye, transcorneal, transscleral, transpalpebral, transorbital electrical stimulation) on different retinal diseases, including retinitis pigmentosa, retinal degeneration, high-intraocular pressure injury, traumatic optic neuropathy, nonarteritic ischemic optic neuropathy. NES could effectively delay degeneration and apoptosis of retinal neurons, preserve retinal structure and visual function with high security, and its mechanism of action might be related to promoting the secretion of neurotrophins and growth factors, decreasing inflammation, inhibiting apoptosis. The quality scores of included studies ranged from 5 to 8 points (a total of 10 points), according to SYRCLE's risk of bias tool. CONCLUSION: This systematic review indicated that NES exerts neuroprotective effects on retinal disease models mainly through its neurotrophic, anti-inflammatory, and anti-apoptotic capabilities. To assess the efficacy of NES in a therapeutic setting, however, well-designed clinical trials are required in the future.


Assuntos
Estimulação Elétrica , Doenças Retinianas , Humanos , Projetos de Pesquisa , Retina , Degeneração Retiniana , Doenças Retinianas/terapia
7.
Ann Bot ; 2024 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-39212622

RESUMO

BACKGROUND AND AIMS: Durum wheat, Triticum turgidum, and bread wheat, Triticum aestivum, are two allopolyploid species of very recent origin that have been subjected to intense selection programs during the thousands of years they have been cultivated. In this paper, we study the durum wheat satellitome and establish a comparative analysis with the previously published bread wheat satellitome. METHODS: We revealed the durum wheat satellitome using the satMiner protocol which is based on consecutive rounds of clustering of Illumina reads by RepeatExplorer2, and estimated abundance and variation for each identified satDNA with RepeatMasker v4.0.5. We have also performed a deep satDNA families characterization including chromosomal location by Fluorescence In Situ Hybridization (FISH) in durum wheat and its comparison with FISH patterns in bread wheat. Basic Local Alignment Search Tool (BLAST®) was used for trailing each satDNA in the assembly of durum wheat genome through NCBI's Genome Data Viewer (GDW) and the genome assemblies of both species were compared. Sequence divergence and consensus turnover rate (CTR) between homologous satDNA families of durum and bread wheat were estimated using MEGA11. KEY RESULTS: This study reveals that in an exceedingly short period, significant qualitative and quantitative changes have occurred in the set of satellite DNAs (satDNAs) of both species, with expansions/contractions of the number of repeats and the loci per satellite, different in each species, and a high rate of sequence change for most of these satellites, in addition to the emergence/loss of satDNAs not shared between the two species analysed. These evolutionary changes in satDNA are common between species but what is truly remarkable and novel about this study is that these processes have taken place in less than the last ~8000 years separating the two species, indicating an accelerated evolution of their satDNAs. CONCLUSIONS: These results, together with the relationship of many of these satellites with transposable elements and the polymorphisms they generate at the level of centromeres and subtelomeric regions of their chromosomes, are analysed and discussed in the context of the evolutionary origin of these species and the selection pressure exerted by man throughout the history of their cultivation.

8.
Exp Brain Res ; 242(9): 2083-2091, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38963560

RESUMO

Transcranial electrical stimulation (tES) often targets the EEG-guided C3/C4 area that may not accurately represent M1 for hand muscles. This study aimed to determine if the neuroanatomy-based scalp acupuncture-guided site (AC) was a more effective spot than the C3 site for neuromodulation. Fifteen healthy subjects received one 20-minute session of high-definition transcranial alternating current stimulation (HD-tACS) intervention (20 Hz at 2 mA) at the AC or C3 sites randomly with a 1-week washout period. Subjects performed ball-squeezing exercises with the dominant hand during the HD-tACS intervention. The AC site was indiscernible from the finger flexor hotspot detected by TMS. At the baseline, the MEP amplitude from finger flexors was greater with less variability at the AC site than at the C3 site. HD-tACS intervention at the AC site significantly increased the MEP amplitude. However, no significant changes were observed after tACS was applied to the C3 site. Our results provide evidence that HD-tACS at the AC site produces better neuromodulation effects on the flexor digitorum superficialis (FDS) muscle compared to the C3 site. The AC localization approach can be used for future tES studies.


Assuntos
Potencial Evocado Motor , Mãos , Couro Cabeludo , Estimulação Transcraniana por Corrente Contínua , Humanos , Masculino , Feminino , Estimulação Transcraniana por Corrente Contínua/métodos , Adulto , Mãos/fisiologia , Couro Cabeludo/fisiologia , Adulto Jovem , Potencial Evocado Motor/fisiologia , Músculo Esquelético/fisiologia , Eletromiografia , Córtex Motor/fisiologia , Eletroencefalografia/métodos
9.
Sensors (Basel) ; 24(12)2024 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-38931778

RESUMO

Transition-edge sensor (TES) microcalorimeters are advanced cryogenic detectors that use a superconducting film for particle or photon detection. We are establishing a new production line for TES detectors to serve as cryogenic anticoincidence (i.e., veto) devices. These detectors are made with a superconducting bilayer of titanium (Ti) and gold (Au) thin films deposited via electron beam evaporation in a high vacuum condition on a monocrystalline silicon substrate. In this work, we report on the development of such sensors, aiming to achieve stable sensing performance despite the effects of aging. For this purpose, patterned and non-patterned Ti/Au bilayer samples with varying geometries and thicknesses were fabricated using microfabrication technology. To characterize the detectors, we present and discuss initial results from repeated resistance-temperature (R-T) measurements over time, conducted on different samples, thereby augmenting existing literature data. Additionally, we present a discussion of the sensor's degradation over time due to aging effects and test a potential remedy based on an easy annealing procedure. In our opinion, this work establishes the groundwork for our new TES detector production line.

10.
Acta Neuropsychiatr ; : 1-5, 2024 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-39355959

RESUMO

Applying transcranial alternating current stimulation (tACS) at 40 Hz to the frontal and parietal regions, either unilaterally (left or right) or bilaterally, can improve cognitive dysfunctions. This study aimed to explore the influence of tACS at gamma frequency over right fronto-parietal (FP) region on attention. The analysis is based on retrospective data from a clinical intervention. We administered test of variables of attention (TOVA; visual mode) to 44 participants with various neuropsychiatric diagnoses before and after 12 sessions of tACS treatment. Alternating currents at 2.0 mA were delivered to the electrode positions F4 and P4, following the 10-20 EEG convention, for 20 mins in each session. We observed significant improvement across 3 indices of the TOVA, including reduction of variability in reaction time (p = 0.0002), increase in d-Prime (separability of targets and non-targets; p = 0.0157), and decrease in commission error rate (p = 0.0116). The mean RT and omission error rate largely remained unchanged. Artificial injection of tACS at 40 Hz over right FP network may improve attention function, especially in the domains of consistency in performance, target/non-target discrimination, and inhibitory control.

11.
Plant J ; 111(5): 1397-1410, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35792830

RESUMO

Transposable elements (TEs) constitute a large proportion of genomes of multicellular eukaryotes, including flowering plants. TEs are normally maintained in a silenced state and their transpositions rarely occur. Hybridization between distant species has been regarded as a 'shock' that stimulates genome reorganization, including TE mobilization. However, whether crosses between genetically close parents that result in viable and fertile offspring can induce TE transpositions has remained unclear. Here, we investigated the activation of long terminal repeat (LTR) retrotransposons in three Lotus japonicus recombinant inbred line (RIL) populations. We found that at least six LTR retrotransposon families were activated and transposed in 78% of the RILs investigated. LORE1a, one of the transposed LTR retrotransposons, showed transgenerational epigenetic activation, indicating the long-term effects of epigenetic instability induced by hybridization. Our study highlights TE activation as an unexpectedly common event in plant reproduction.


Assuntos
Lotus , Retroelementos , Evolução Molecular , Genoma de Planta/genética , Hibridização Genética , Lotus/genética , Plantas/genética , Retroelementos/genética , Sequências Repetidas Terminais/genética
12.
BMC Genomics ; 24(1): 36, 2023 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-36658480

RESUMO

BACKGROUND: Several studies showed genome-wide DNA methylation during Arabidopsis embryogenesis and germination. Although it has been known that the change of DNA methylation mainly occurs at CHH context mediated by small RNA-directed DNA methylation pathway during seed ripening and germination, the causality of the methylation difference exhibited in natural Arabidopsis ecotypes has not been thoroughly studied. RESULTS: In this study we compared DNA methylation difference using comparative pairwise multi-omics dynamics in Columbia-0 (Col) and Cape Verde Island (Cvi) ecotypes. Arabidopsis genome was divided into two regions, common regions in both ecotypes and Col-specific regions, depending on the reads mapping of whole genome bisulfite sequencing libraries from both ecotypes. Ecotype comparison was conducted within common regions and the levels of DNA methylation on common regions and Col-specific regions were also compared. we confirmed transcriptome were relatively dynamic in stage-wise whereas the DNA methylome and small RNAome were more ecotype-dependent. While the global CG methylation remains steady during maturation and germination, we found genic CG methylation differs the most between the two accessions. We also found that ecotype-specific differentially methylated regions (eDMR) are positively correlated with ecotype-specifically expressed 24-nt small RNA clusters. In addition, we discovered that Col-specific regions enriched with transposable elements (TEs) and structural variants that tend to become hypermethylated, and TEs in Col-specific regions were longer in size, more pericentromeric, and more hypermethylated than those in the common regions. Through the analysis of RdDM machinery mutants, we confirmed methylation on Col-specific region as well as on eDMRs in common region are contributed by RdDM pathway. Lastly, we demonstrated that highly variable sequences between ecotypes (HOT regions) were also affected by RdDM-mediated regulation. CONCLUSIONS: Through ecotype comparison, we revealed differences and similarities of their transcriptome, methylome and small RNAome both in global and local regions. We validated the contribution of RdDM causing differential methylation of common regions. Hypermethylated ecotype-specific regions contributed by RNA-directed DNA methylation pathway largely depend on the presence of TEs and copy-gain structural variations. These ecotype-specific regions are frequently associated with HOT regions, providing evolutionary insights into the epigenome dynamics within a species.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , Arabidopsis/genética , Arabidopsis/metabolismo , Ecótipo , Inativação Gênica , Metilação de DNA , Proteínas de Arabidopsis/genética , RNA Interferente Pequeno/genética , Regulação da Expressão Gênica de Plantas
13.
BMC Genomics ; 24(1): 350, 2023 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-37365554

RESUMO

BACKGROUND: Poa annua (annual bluegrass) is an allotetraploid turfgrass, an agronomically significant weed, and one of the most widely dispersed plant species on earth. Here, we report the chromosome-scale genome assemblies of P. annua's diploid progenitors, P. infirma and P. supina, and use multi-omic analyses spanning all three species to better understand P. annua's evolutionary novelty. RESULTS: We find that the diploids diverged from their common ancestor 5.5 - 6.3 million years ago and hybridized to form P. annua ≤ 50,000 years ago. The diploid genomes are similar in chromosome structure and most notably distinguished by the divergent evolutionary histories of their transposable elements, leading to a 1.7 × difference in genome size. In allotetraploid P. annua, we find biased movement of retrotransposons from the larger (A) subgenome to the smaller (B) subgenome. We show that P. annua's B subgenome is preferentially accumulating genes and that its genes are more highly expressed. Whole-genome resequencing of several additional P. annua accessions revealed large-scale chromosomal rearrangements characterized by extensive TE-downsizing and evidence to support the Genome Balance Hypothesis. CONCLUSIONS: The divergent evolutions of the diploid progenitors played a central role in conferring onto P. annua its remarkable phenotypic plasticity. We find that plant genes (guided by selection and drift) and transposable elements (mostly guided by host immunity) each respond to polyploidy in unique ways and that P. annua uses whole-genome duplication to purge highly parasitized heterochromatic sequences. The findings and genomic resources presented here will enable the development of homoeolog-specific markers for accelerated weed science and turfgrass breeding.


Assuntos
Poa , Poa/genética , Elementos de DNA Transponíveis , Melhoramento Vegetal , Genes de Plantas , Poliploidia , Genoma de Planta , Evolução Molecular
14.
Neuroimage ; 280: 120331, 2023 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-37604295

RESUMO

Designing a transcranial electrical stimulation (tES) strategy requires considering multiple objectives, such as intensity in the target area, focality, stimulation depth, and avoidance zone. These objectives are often mutually exclusive. In this paper, we propose a general framework, called multi-objective optimization via evolutionary algorithm (MOVEA), which solves the non-convex optimization problem in designing tES strategies without a predefined direction. MOVEA enables simultaneous optimization of multiple targets through Pareto optimization, generating a Pareto front after a single run without manual weight adjustment and allowing easy expansion to more targets. This Pareto front consists of optimal solutions that meet various requirements while respecting trade-off relationships between conflicting objectives such as intensity and focality. MOVEA is versatile and suitable for both transcranial alternating current stimulation (tACS) and transcranial temporal interference stimulation (tTIS) based on high definition (HD) and two-pair systems. We comprehensively compared tACS and tTIS in terms of intensity, focality, and steerability for targets at different depths. Our findings reveal that tTIS enhances focality by reducing activated volume outside the target by 60%. HD-tTIS and HD-tDCS can achieve equivalent maximum intensities, surpassing those of two-pair tTIS, such as 0.51 V/m under HD-tACS/HD-tTIS and 0.42 V/m under two-pair tTIS for the motor area as a target. Analysis of variance in eight subjects highlights individual differences in both optimal stimulation policies and outcomes for tACS and tTIS, emphasizing the need for personalized stimulation protocols. These findings provide guidance for designing appropriate stimulation strategies for tACS and tTIS. MOVEA facilitates the optimization of tES based on specific objectives and constraints, advancing tTIS and tACS-based neuromodulation in understanding the causal relationship between brain regions and cognitive functions and treating diseases. The code for MOVEA is available at https://github.com/ncclabsustech/MOVEA.


Assuntos
Estimulação Transcraniana por Corrente Contínua , Humanos , Encéfalo , Cognição , Algoritmos , Evolução Biológica
15.
Neuroimage ; 279: 120343, 2023 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-37619797

RESUMO

Non-human primates (NHPs) have become key for translational research in noninvasive brain stimulation (NIBS). However, in order to create comparable stimulation conditions for humans it is vital to study the accuracy of current modeling practices across species. Numerical models to simulate electric fields are an important tool for experimental planning in NHPs and translation to human studies. It is thus essential whether and to what extent the anatomical details of NHP models agree with current modeling practices when calculating NIBS electric fields. Here, we create highly accurate head models of two non-human primates (NHP) MR data. We evaluate how muscle tissue and head field of view (depending on MRI parameters) affect simulation results in transcranial electric and magnetic stimulation (TES and TMS). Our findings indicate that the inclusion of anisotropic muscle can affect TES electric field strength up to 22% while TMS is largely unaffected. Additionally, comparing a full head model to a cropped head model illustrates the impact of head field of view on electric fields for both TES and TMS. We find opposing effects between TES and TMS with an increase up to 24.8% for TES and a decrease up to 24.6% for TMS for the cropped head model compared to the full head model. Our results provide important insights into the level of anatomical detail needed for NHP head models and can inform future translational efforts for NIBS studies.


Assuntos
Eletricidade , Primatas , Animais , Humanos , Anisotropia , Simulação por Computador , Encéfalo
16.
Neuroimage ; 281: 120379, 2023 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-37716590

RESUMO

BACKGROUND: Electric field (E-field) modeling is a potent tool to estimate the amount of transcranial magnetic and electrical stimulation (TMS and tES, respectively) that reaches the cortex and to address the variable behavioral effects observed in the field. However, outcome measures used to quantify E-fields vary considerably and a thorough comparison is missing. OBJECTIVES: This two-part study aimed to examine the different outcome measures used to report on tES and TMS induced E-fields, including volume- and surface-level gray matter, region of interest (ROI), whole brain, geometrical, structural, and percentile-based approaches. The study aimed to guide future research in informed selection of appropriate outcome measures. METHODS: Three electronic databases were searched for tES and/or TMS studies quantifying E-fields. The identified outcome measures were compared across volume- and surface-level E-field data in ten tES and TMS modalities targeting two common targets in 100 healthy individuals. RESULTS: In the systematic review, we extracted 308 outcome measures from 202 studies that adopted either a gray matter volume-level (n = 197) or surface-level (n = 111) approach. Volume-level results focused on E-field magnitude, while surface-level data encompassed E-field magnitude (n = 64) and normal/tangential E-field components (n = 47). E-fields were extracted in ROIs, such as brain structures and shapes (spheres, hexahedra and cylinders), or the whole brain. Percentiles or mean values were mostly used to quantify E-fields. Our modeling study, which involved 1,000 E-field models and > 1,000,000 extracted E-field values, revealed that different outcome measures yielded distinct E-field values, analyzed different brain regions, and did not always exhibit strong correlations in the same within-subject E-field model. CONCLUSIONS: Outcome measure selection significantly impacts the locations and intensities of extracted E-field data in both tES and TMS E-field models. The suitability of different outcome measures depends on the target region, TMS/tES modality, individual anatomy, the analyzed E-field component and the research question. To enhance the quality, rigor, and reproducibility in the E-field modeling domain, we suggest standard reporting practices across studies and provide four recommendations.


Assuntos
Encéfalo , Estimulação Transcraniana por Corrente Contínua , Humanos , Reprodutibilidade dos Testes , Encéfalo/fisiologia , Córtex Cerebral , Eletricidade , Substância Cinzenta , Estimulação Magnética Transcraniana/métodos , Estimulação Transcraniana por Corrente Contínua/métodos
17.
Curr Issues Mol Biol ; 45(1): 490-500, 2023 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-36661518

RESUMO

Testin is a protein expressed in normal human tissues, being responsible, with other cytoskeleton proteins, for the proper functioning of cell−cell junction areas and focal adhesion plaques. It takes part in the regulation of actin filament changes during cell spreading and motility. Loss of heterozygosity in the testin-encoding gene results in altered protein expression in many malignancies, as partly described for cervical cancer. The aim of our study was the assessment of the immunohistochemical (IHC) expression of testin in cervical cancer and its analysis in regard to clinical data as well the expression of the Ki-67 antigen and p16 protein. Moreover, testin expression was assessed by Western blot (WB) in commercially available cell lines. The IHC analysis disclosed that the expression of testin inversely correlated with p16 (r = −0.2104, p < 0.0465) and Ki-67 expression (r = −0.2359, p < 0.0278). Moreover, weaker testin expression was observed in cancer cases vs. control ones (p < 0.0113). The WB analysis of testin expression in the cervical cancer cell lines corresponded to the IHC results and showed a weaker expression compared to that in the control cell line. When we compared the expression of testin in cervical cancer cell lines, we found a weaker expression in HPV-negative cell lines. In summary, we found that the intensity of testin expression and the number of positive cells inversely correlated with the expression of Ki-67 (a marker of proliferation) and p16 (a marker of cell cycle dysregulation). This study shows that the combined assessment of testin, Ki-67 and p16 expression may improve cervical cancer diagnostics.

18.
Mol Genet Genomics ; 298(5): 1045-1058, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37269361

RESUMO

Transposable elements (TEs) are genetic elements that have evolved as crucial regulators of human development and cancer, functioning as both genes and regulatory elements. When TEs become dysregulated in cancer cells, they can serve as alternate promoters to activate oncogenes, a process known as onco-exaptation. This study aimed to explore the expression and epigenetic regulation of onco-exaptation events in early human developmental tissues. We discovered co-expression of some TEs and oncogenes in human embryonic stem cells and first trimester and term placental tissues. Previous studies identified onco-exaptation events in various cancer types, including an AluJb SINE element-LIN28B interaction in lung cancer cells, and showed that the TE-derived LIN28B transcript is associated with poor patient prognosis in hepatocellular carcinoma. This study further characterized the AluJb-LIN28B transcript and confirmed that its expression is restricted to the placenta. Targeted DNA methylation analysis revealed differential methylation of the two LIN28B promoters between placenta and healthy somatic tissues, indicating that some TE-oncogene interactions are not cancer-specific but arise from the epigenetic reactivation of developmental TE-derived regulatory events. In conclusion, our findings provide evidence that some TE-oncogene interactions are not limited to cancer and may originate from the epigenetic reactivation of TE-derived regulatory events that are involved in early development. These insights broaden our understanding of the role of TEs in gene regulation and suggest the potential importance of targeting TEs in cancer therapy beyond their conventional use as cancer-specific markers.


Assuntos
Elementos de DNA Transponíveis , Neoplasias , Gravidez , Humanos , Feminino , Epigênese Genética , Placenta , Sequências Reguladoras de Ácido Nucleico , Neoplasias/genética , Proteínas de Ligação a RNA/genética
19.
J Neurosci Res ; 101(4): 405-423, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36537991

RESUMO

There is substantial intersubject variability of behavioral and neurophysiological responses to transcranial electrical stimulation (tES), which represents one of the most important limitations of tES. Many tES protocols utilize a fixed experimental parameter set disregarding individual anatomical and physiological properties. This one-size-fits-all approach might be one reason for the observed interindividual response variability. Simulation of current flow applying head models based on available anatomical data can help to individualize stimulation parameters and contribute to the understanding of the causes of this response variability. Current flow modeling can be used to retrospectively investigate the characteristics of tES effectivity. Previous studies examined, for example, the impact of skull defects and lesions on the modulation of current flow and demonstrated effective stimulation intensities in different age groups. Furthermore, uncertainty analysis of electrical conductivities in current flow modeling indicated the most influential tissue compartments. Current flow modeling, when used in prospective study planning, can potentially guide stimulation configurations resulting in individually effective tES. Specifically, current flow modeling using individual or matched head models can be employed by clinicians and scientists to, for example, plan dosage in tES protocols for individuals or groups of participants. We review studies that show a relationship between the presence of behavioral/neurophysiological responses and features derived from individualized current flow models. We highlight the potential benefits of individualized current flow modeling.


Assuntos
Estimulação Transcraniana por Corrente Contínua , Humanos , Estimulação Transcraniana por Corrente Contínua/métodos , Estudos Prospectivos , Estudos Retrospectivos , Simulação por Computador , Encéfalo/fisiologia
20.
Genome ; 66(7): 193-201, 2023 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-37120861

RESUMO

Genome size evolution is known to be related with transposable elements, yet such relation in incipient species remains poorly understood. For decades, the willistoni subgroup of Drosophila has been a model for evolutionary studies because of the different evolutionary stages and degrees of reproductive isolation its species present. Our main question here was how speciation influences genome size evolution and the fraction of repetitive elements, with a focus on transposable elements. We quantitatively compared the mobilome of four species and two subspecies belonging to this subgroup with their genome size, and performed comparative phylogenetic analyses. Our results showed that genome size and the fraction of repetitive elements evolved according to the evolutionary history of these species, but the content of transposable elements showed some discrepancies. Signals of recent transposition events were detected for different superfamilies. Their low genomic GC content suggests that in these species transposable element mobilization might be facilitated by relaxed natural selection. Additionally, a possible role of the superfamily DNA/TcMar-Tigger in the expansion of these genomes was also detected. We hypothesize that the undergoing process of speciation could be promoting the observed increase in the fraction of repetitive elements and, consequently, genome size.


Assuntos
Elementos de DNA Transponíveis , Drosophila , Animais , Drosophila/genética , Tamanho do Genoma , Filogenia , Genômica , Evolução Molecular
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