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1.
Mol Biol Evol ; 40(6)2023 06 01.
Artículo en Inglés | MEDLINE | ID: mdl-37247387

RESUMEN

Recent genomic analyses of evolutionary radiations suggest that ancient introgression may facilitate rapid diversification and adaptive radiation. The loach genus Triplophysa, a genus with most species endemic to Tibetan Plateau, shows ecological diversity and rapid evolution and represents a potential example of adaptive radiation linked to the uplift of the Tibetan Plateau. Here, we interrogate the complex evolutionary history of Triplophysa fishes through the analysis of whole-genome sequences. By reconstructing the phylogeny of Triplophysa, quantifying introgression across this clade, and simulating speciation and migration processes, we confirm that extensive gene flow events occurred across disparate Triplophysa species. Our results suggest that introgression plays a more substantial role than incomplete lineage sorting in underpinning phylogenetic discordance in Triplophysa. The results also indicate that genomic regions affected by ancient gene flow exhibit characteristics of lower recombination rates and nucleotide diversity and may associate with selection. Simulation analysis of Triplophysa tibetana suggests that the species may have been affected by the Gonghe Movement in the third uplift of the Tibetan Plateau, resulting in founder effects and a subsequent reduction in Ne.


Asunto(s)
Altitud , Cipriniformes , Animales , Filogenia , Tibet , Cipriniformes/genética , Adaptación Fisiológica/genética
2.
BMC Plant Biol ; 24(1): 610, 2024 Jun 27.
Artículo en Inglés | MEDLINE | ID: mdl-38926660

RESUMEN

BACKGROUND: During male gametogenesis of flowering plants, sperm cell lineage (microspores, generative cells, and sperm cells) differentiated from somatic cells and acquired different cell fates. Trimethylation of histone H3 on lysine 4 (H3K4me3) epigenetically contributes to this process, however, it remained unclear how H3K4me3 influences the gene expression in each cell type. Here, we conducted chromatin immunoprecipitation sequencing (ChIP-seq) to obtain a genome-wide landscape of H3K4me3 during sperm cell lineage development in tomato (Solanum lycopersicum). RESULTS: We show that H3K4me3 peaks were mainly enriched in the promoter regions, and intergenic H3K4me3 peaks expanded as sperm cell lineage differentiated from somatic cells. H3K4me3 was generally positively associated with transcript abundance and served as a better indicator of gene expression in somatic and vegetative cells, compared to sperm cell lineage. H3K4me3 was mutually exclusive with DNA methylation at 3' proximal of the transcription start sites. The microspore maintained the H3K4me3 features of somatic cells, while generative cells and sperm cells shared an almost identical H3K4me3 pattern which differed from that of the vegetative cell. After microspore division, significant loss of H3K4me3 in genes related to brassinosteroid and cytokinin signaling was observed in generative cells and vegetative cells, respectively. CONCLUSIONS: Our results suggest the asymmetric division of the microspore significantly reshapes the genome-wide distribution of H3K4me3. Selective loss of H3K4me3 in genes related to hormone signaling may contribute to functional differentiation of sperm cell lineage. This work provides new resource data for the epigenetic studies of gametogenesis in plants.


Asunto(s)
Histonas , Solanum lycopersicum , Solanum lycopersicum/genética , Solanum lycopersicum/crecimiento & desarrollo , Solanum lycopersicum/metabolismo , Histonas/metabolismo , Linaje de la Célula , Genoma de Planta , Metilación de ADN , Regulación de la Expresión Génica de las Plantas , Polen/genética , Polen/crecimiento & desarrollo , Epigénesis Genética , Secuenciación de Inmunoprecipitación de Cromatina
3.
J Biomed Sci ; 31(1): 15, 2024 Jan 23.
Artículo en Inglés | MEDLINE | ID: mdl-38263133

RESUMEN

BACKGROUND: CDGSH iron-sulfur domain-containing protein 2 (CISD2), a pro-longevity gene, mediates healthspan in mammals. CISD2 is down-regulated during aging. Furthermore, a persistently high level of CISD2 promotes longevity and ameliorates an age-related skin phenotype in transgenic mice. Here we translate the genetic evidence into a pharmaceutical application using a potent CISD2 activator, hesperetin, which enhances CISD2 expression in HEK001 human keratinocytes from an older person. We also treated naturally aged mice in order to study the activator's anti-aging efficacy. METHODS: We studied the biological effects of hesperetin on aging skin using, firstly, a cell-based platform, namely a HEK001 human keratinocyte cell line established from an older person. Secondly, we used a mouse model, namely old mice at 21-month old. In the latter case, we investigate the anti-aging efficacy of hesperetin on ultraviolet B (UVB)-induced photoaging and naturally aged skin. Furthermore, to identify the underlying mechanisms and potential biological pathways involved in this process we carried out transcriptomic analysis. Finally, CISD2 knockdown HEK001 keratinocytes and Cisd2 knockout mice were used to study the Cisd2-dependent effects of hesperetin on skin aging. RESULTS: Four findings are pinpointed. Firstly, in human skin, CISD2 is mainly expressed in proliferating keratinocytes from the epidermal basal layer and, furthermore, CISD2 is down-regulated in the sun-exposed epidermis. Secondly, in HEK001 human keratinocytes from an older person, hesperetin enhances mitochondrial function and protects against reactive oxygen species-induced oxidative stress via increased CISD2 expression; this enhancement is CISD2-dependent. Additionally, hesperetin alleviates UVB-induced damage and suppresses matrix metalloproteinase-1 expression, the latter being a major indicator of UVB-induced damage in keratinocytes. Thirdly, transcriptomic analysis revealed that hesperetin modulates a panel of differentially expressed genes that are associated with mitochondrial function, redox homeostasis, keratinocyte function, and inflammation in order to attenuate senescence. Intriguingly, hesperetin activates two known longevity-associated regulators, namely FOXO3a and FOXM1, in order to suppress the senescence-associated secretory phenotype. Finally, in mouse skin, hesperetin enhances CISD2 expression to ameliorate UVB-induced photoaging and this occurs via a mechanism involving CISD2. Most strikingly, late-life treatment with hesperetin started at 21-month old and lasting for 5 months, is able to retard skin aging and rejuvenate naturally aged skin in mice. CONCLUSIONS: Our results reveal that a pharmacological elevation of CISD2 expression at a late-life stage using hesperetin treatment is a feasible approach to effectively mitigating both intrinsic and extrinsic skin aging and that hesperetin could act as a functional food or as a skincare product for fighting skin aging.


Asunto(s)
Hesperidina , Envejecimiento de la Piel , Anciano , Animales , Humanos , Ratones , Queratinocitos , Mamíferos , Ratones Transgénicos
4.
J Plant Res ; 2024 Mar 20.
Artículo en Inglés | MEDLINE | ID: mdl-38506958

RESUMEN

The intervention of nectar robbers in plant pollination systems will cause some pollinators to modify their foraging behavior to act as secondary robbers, consequently adopting a mixed foraging strategy. The influence of nectar robbing on pollinator behavior may be affected by spatio-temporal difference of robbing intensity, and consequently, may have different effects on the pollination of host plants. However, whether and how the nectar robbing might influence pollinators under different robbing intensity still needs further investigation. In this study, Symphytum officinale was used to detect the effect of nectar robbers on pollinators under different robbing intensity as well as their effects on plant reproductive success. Six robbing levels and three bumblebees with mixed foraging behaviors were used to evaluate the effect of different robbing intensity on pollinator behavior, visitation rate, flower longevity and pollen deposition. Our results indicated that the robbing rate increased gradually with the proportion of robbed flowers, but which did not affect the frequency of legitimate visits. The increase of robbing rate promoted the corolla abscission, and then enhanced the self-pollen deposition, but which had no significant effect on cross-pollen deposition. These results indicate that the overall fitness of S. officinale was improved by combined self and cross-pollination modes when visited by both pollinators and nectar robbers simultaneously. Although nectar robbing is not uncommon, its consequences for pollination in the interaction web have not been well studied. Our results emphasize the significance of indirect impacts in mediating the adaptive outcomes of species interactions.

5.
Plant J ; 111(5): 1283-1295, 2022 09.
Artículo en Inglés | MEDLINE | ID: mdl-35765221

RESUMEN

Pollen exine is composed of finely-organized nexine, bacula and tectum, and is crucial for pollen viability and function. Pollen exine development involves a complicated molecular network that coordinates the interaction between pollen and tapetal cells, as well as the biosynthesis, transport and assembly of sporopollenin precursors; however, our understanding of this network is very limited. Here, we report the roles of PEM1, a member of methyl-CpG-binding domain family, in rice pollen development. PEM1 expressed constitutively and, in anthers, its expression was detectable in tapetal cells and pollen. This predicted PEM1 protein of 240 kDa had multiple epigenetic-related domains. pem1 mutants exhibited abnormal Ubisch bodies, delayed exine occurrence and, finally, defective exine, including invisible bacula, amorphous and thickened nexine and tectum layer structures, and also had the phenotype of increased anther cuticle. The mutation in PEM1 did not affect the timely degradation of tapetum. Lipidomics revealed much higher wax and cutin contents in mutant anthers than in wild-type. Accordingly, this mutation up-regulated the expression of a set of genes implicated in transcriptional repression, signaling and diverse metabolic pathways. These results indicate that PEM1 mediates Ubisch body formation and pollen exine development mainly by negatively modulating the expression of genes. Thus, the PEM1-mediated molecular network represents a route for insights into mechanisms underlying pollen development. PEM1 may be a master regulator of pollen exine development.


Asunto(s)
Oryza , Familia , Regulación de la Expresión Génica de las Plantas , Mutación , Oryza/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Polen/metabolismo
6.
New Phytol ; 240(3): 1052-1065, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37615062

RESUMEN

Grain notching is a common deformation that decreases rice (Oryza sativa) quality; however, the underlying molecular basis causing grain notching remains unclear. We report mechanisms underlying grain notching in Small and notched grain (Sng) mutants, which contained an arginine to histidine substitution at amino acid position 422 (R422H) of the α-tubulin protein OsTUBA3. The R422H mutation decreased cell length and increased cell width/height of glumes and caryopses, but led to elongated caryopses compressed within shortened glumes, thus giving rise to notched and small grains. Glume and caryopsis cells had different dimensional orientations relative to the directions of organ elongation. Thus, the abnormal cell expansion induced in glumes and caryopses by the R422H mutation had different effects on elongation of these organs. The R422H mutation in OsTUBA3 compromised ß-tubulin binding and led to formation of defective heterodimers. This in turn affected tubulin incorporation and microtubule (MT) nucleation and regrowth, consequently leading to MT instability and reducing the transverse orientation. The defective MT dynamics affected cell expansion and shape, causing different alterations in glume and caryopsis dimensions and resulting in grain notching. These data indicate that Arg422 in OsTUBA3 is crucial for MT dynamics and that substitution with His causes grain notching, reducing grain quality and yield. These findings offer valuable insights into the molecular regulation underlying grain development in rice.

7.
BMC Cancer ; 23(1): 1163, 2023 Nov 29.
Artículo en Inglés | MEDLINE | ID: mdl-38031068

RESUMEN

BACKGROUND: The NOD-, LRR- and pyrin domain­containing 3 (NLRP3) inflammasome is a critical component of the innate immune system. It has been known to play an important role in the carcinogenesis and prognosis of breast cancer patients. While the clinical evidence of the relationship between NLRP3 inflammasome activation and long-term survival is still limited, the possible roles of parenchymal or immune-stromal cells of breast cancer tissues in contributing to such carcinogenesis and progression still need to be clarified. This study is an analysis of patients receiving breast cancer surgery in a previous clinical trial. METHODS: Immunohistochemistry (IHC) was used to detect the expression levels of NLRP3 inflammasome pathway-related proteins, including NLRP3, caspase-1, apoptosis-associated speck-like protein (ASC), IL-1ß, and IL-18, in parenchymal and immune-stromal cells of breast cancer tissues compared to those of adjacent normal tissues, respectively. The relationship between NLRP3 inflammasome expression and clinicopathological characteristics, as well as 5-year survivals were analyzed using the Chi-square test, Kaplan-Meier survival curves, and Cox regression analysis. RESULTS: In the parenchymal cells, ASC and IL-18 protein levels were significantly up-regulated in breast cancer tissues compared with adjacent normal tissues (P<0.05). In the immune-stromal cells, all the five NLRP3 inflammasome pathway-related proteins were significantly elevated in breast cancer tissues compared with adjacent normal tissues (P < 0.05). Carcinoma cell embolus was found to significantly correlate with high NLRP3 expression in parenchymal cells of the tumor (x2=4.592, P=0.032), while the expression of caspase-1 was negatively correlated with tumor progression. Histological grades were found to have a positive correlation with IL-18 expression in immune-stromal cells of the tumor (x2=14.808, P=0.001). Kaplan-Meier survival analysis revealed that high IL-18 expression in the immune-stromal cells and the positive carcinoma cell embolus were both associated with poor survival (P < 0.05). The multivariable Cox proportional hazards regression model implied that the high IL-18 expression and positive carcinoma cell embolus were both independent risk factors for unfavorable prognosis. CONCLUSIONS: The activation of NLRP3 inflammasome pathways in immune-stromal and tumor parenchymal cells in the innate immune system was not isotropic and the main functions are somewhat different in breast cancer patients. Caspase-1 in parenchymal cells of the tumor was negatively correlated with tumor progression, and upregulation of IL-18 in immune-stromal cells of breast cancer tissues is a promising prognostic biomarker and a potential immunotherapy target. TRIAL REGISTRATION: This clinical trial has been registered at the Chictr.org.cn registry system on 21/08/2018 (ChiCTR1800017910).


Asunto(s)
Neoplasias de la Mama , Carcinoma , Embolia , Humanos , Femenino , Inflamasomas/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Interleucina-18 , Neoplasias de la Mama/terapia , Caspasa 1/metabolismo , Carcinogénesis , Interleucina-1beta/metabolismo
8.
Plant J ; 105(3): 565-579, 2021 02.
Artículo en Inglés | MEDLINE | ID: mdl-33249677

RESUMEN

During the sexual reproduction of higher plants, DNA methylation and transcription are broadly changed to reshape a microspore into two sperm cells (SCs) and a vegetative cell (VC). However, when and how the DNA methylation of SCs is established remains not fully understood. Here we investigate the DNA methylation (5 mC) dynamics of SC lineage and the VC in tomato using whole-genome bisulfite sequencing. We find the asymmetric division of the microspore gives its two daughter cells differential methylome. Compared with the generative cell (GC), the VC is hypomethylated at CG sites while hypermethylated at CHG and CHH sites, with the majority of differentially methylation regions targeted to transposable elements (TEs). SCs have a nearly identical DNA methylome to the GC, suggesting that the methylation landscape in SCs may be pre-established following the asymmetric division or inherited from the GC. The random forest classifier for predicting gene and TE expression shows that methylation within the gene body is a more powerful predictor for gene expression. Among all tested samples, gene and TE expression in the microspore may be more predictable by DNA methylation. Our results depict an intact DNA methylome landscape of SC lineage in higher plants, and reveal that the impact of DNA methylation on transcription is variant in different cell types.


Asunto(s)
Metilación de ADN , Solanum lycopersicum/citología , Solanum lycopersicum/genética , Linaje de la Célula , Citosina/metabolismo , Elementos Transponibles de ADN , Regulación de la Expresión Génica de las Plantas , Células Vegetales , Hojas de la Planta/genética , Polen/citología
9.
J Exp Bot ; 73(19): 6942-6954, 2022 11 02.
Artículo en Inglés | MEDLINE | ID: mdl-36052968

RESUMEN

Head rice yield (HRY) is an essential quality trait, and is sensitive to environmental stresses during the grain-filling, harvest, and postharvest stages. It is therefore important for rice production and global food security to select for superior HRY traits; however, the molecular basis of this trait remains unknown. Using diverse rice germplasm material, we performed a genome-wide association study of grain fissure resistance (GFR), the phenotype most associated with HRY, and found that the granule-bound starch synthase I gene Waxy is an important gene controlling GFR. Analysis of near-isogenic lines demonstrated that genetic variations in Waxy conferred different levels of tolerance to fissuring in grains. The null allele wx resulted in the highest GFR, while alleles that increased amylose synthesis reduced GFR. Increases in amylose content led to increases in the ratio of the widths of the amorphous layer to the semi-crystalline layer of the starch granules, and also to increased occurrence of chalkiness. The layer structure determined GFR by affecting the degree of swelling of granules in response to moisture, and chalkiness acted as an accelerator of moisture infiltration to rapidly increase the number of swelling granules. Our study reveals the molecular basis of GFR and HRY, thus opening the door for further understanding of the molecular networks of GFR and HRY.


Asunto(s)
Oryza , Almidón Sintasa , Oryza/fisiología , Amilosa , Estudio de Asociación del Genoma Completo , Ceras , Almidón/química , Almidón Sintasa/genética , Grano Comestible/genética
10.
Theor Appl Genet ; 135(8): 2641-2653, 2022 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-35796761

RESUMEN

KEY MESSAGE: Different digenomic Brassica autoallohexaploids were produced from the crosses of three allotetraploids and ancestral diploids and characterized for the cytological behavior of two subgenomes with two and four copies. Interspecific hybridization and allopolyploidization present an important pathway for plant evolution and breeding. In this study, different types of digenomic autoallohexaploids with two or four copies of two subgenomes (AAAACC, AACCCC, AAAABB, BBBBCC, BBCCCC) were synthesized by the crosses between three Brassica allotetraploids and their diploid progenitors and the chromosome doubling, and their meiotic behaviors were analyzed by fluorescence in situ hybridization (FISH). These autoallohexaploids showed some variations in pollen fertility and seed-sets and produced both euploid and aneuploid progenies with some chromosomes lost. Two subgenomes in these autoallohexaploids showed some aberrant pairings and segregations, and the degrees of meiotic regularity were negatively associated with the genome affinities. The chromosomes of the subgenome with four copies formed few quadrivalents with the average number < 2, and mainly paired as bivalents, and majority of the chromosomes from the subgenome with two copies gave the expected bivalents. The different extents of the equal and unequal segregations corresponded to the chromosome pairings. The development and cytological investigation of these autoallohexaploids provide not only the new germplasm for genetic research and breeding but also the new clues for the genome behavior and interplay between these subgenomes with different copies.


Asunto(s)
Brassica , Brassica/genética , Cromosomas de las Plantas/genética , Genoma de Planta , Hibridación Genética , Hibridación Fluorescente in Situ , Fitomejoramiento , Poliploidía
11.
J Biomed Sci ; 29(1): 53, 2022 Jul 24.
Artículo en Inglés | MEDLINE | ID: mdl-35871686

RESUMEN

BACKGROUND: The human CISD2 gene is located within a longevity region mapped on chromosome 4q. In mice, Cisd2 levels decrease during natural aging and genetic studies have shown that a high level of Cisd2 prolongs mouse lifespan and healthspan. Here, we evaluate the feasibility of using a Cisd2 activator as an effective way of delaying aging. METHODS: Hesperetin was identified as a promising Cisd2 activator by herb compound library screening. Hesperetin has no detectable toxicity based on in vitro and in vivo models. Naturally aged mice fed dietary hesperetin were used to investigate the effect of this Cisd2 activator on lifespan prolongation and the amelioration of age-related structural defects and functional decline. Tissue-specific Cisd2 knockout mice were used to study the Cisd2-dependent anti-aging effects of hesperetin. RNA sequencing was used to explore the biological effects of hesperetin on aging. RESULTS: Three discoveries are pinpointed. Firstly, hesperetin, a promising Cisd2 activator, when orally administered late in life, enhances Cisd2 expression and prolongs healthspan in old mice. Secondly, hesperetin functions mainly in a Cisd2-dependent manner to ameliorate age-related metabolic decline, body composition changes, glucose dysregulation, and organ senescence. Finally, a youthful transcriptome pattern is regained after hesperetin treatment during old age. CONCLUSIONS: Our findings indicate that a Cisd2 activator, hesperetin, represents a promising and broadly effective translational approach to slowing down aging and promoting longevity via the activation of Cisd2.


Asunto(s)
Longevidad , Proteínas del Tejido Nervioso , Envejecimiento/genética , Animales , Proteínas Relacionadas con la Autofagia , Hesperidina , Humanos , Longevidad/genética , Ratones , Ratones Noqueados , Proteínas del Tejido Nervioso/genética
12.
J Nat Prod ; 85(11): 2667-2674, 2022 11 25.
Artículo en Inglés | MEDLINE | ID: mdl-36346918

RESUMEN

Chromatographic separation on the liquid-state fermented products produced by the fungal strain Alternaria alstroemeriae Km2286 isolated from the littoral medicinal herb Atriplex maximowicziana Makino resulted in the isolation of compounds 1-9. Structures were determined by spectroscopic analysis as four undescribed perylenequinones, altertromins A-D (1-4), along with altertoxin IV (5), altertoxin VIII (6), stemphyperylenol (7), tenuazonic acid (8), and allo-tenuazonic acid (9). Compounds 1-6 exhibited antiviral activities against Epstein-Barr virus (EBV) with EC50 values ranging from 0.17 ± 0.07 to 3.13 ± 0.31 µM and selectivity indices higher than 10. In an anti-neuroinflammatory assay, compounds 1-4, 6, and 7 showed inhibitory activity of nitric oxide production in lipopolysaccharide-induced microglial BV-2 cells, with IC50 values ranging from 0.33 ± 0.04 to 4.08 ± 0.53 µM without significant cytotoxicity. This is the first report to describe perylenequinone-type compounds with potent anti-EBV and anti-neuroinflammatory activities.


Asunto(s)
Alternaria , Antiinflamatorios , Antivirales , Atriplex , Infecciones por Virus de Epstein-Barr , Herpesvirus Humano 4 , Perileno , Plantas Medicinales , Quinonas , Humanos , Alternaria/química , Alternaria/aislamiento & purificación , Atriplex/microbiología , Infecciones por Virus de Epstein-Barr/virología , Herpesvirus Humano 4/efectos de los fármacos , Estructura Molecular , Perileno/química , Perileno/aislamiento & purificación , Perileno/farmacología , Plantas Medicinales/microbiología , Quinonas/química , Quinonas/aislamiento & purificación , Quinonas/farmacología , Ácido Tenuazónico/química , Antiinflamatorios/química , Antiinflamatorios/aislamiento & purificación , Antiinflamatorios/farmacología , Antivirales/química , Antivirales/aislamiento & purificación , Antivirales/farmacología
13.
Nature ; 538(7625): 397-401, 2016 Oct 20.
Artículo en Inglés | MEDLINE | ID: mdl-27706135

RESUMEN

Transient, multi-protein complexes are important facilitators of cellular functions. This includes the chaperome, an abundant protein family comprising chaperones, co-chaperones, adaptors, and folding enzymes-dynamic complexes of which regulate cellular homeostasis together with the protein degradation machinery. Numerous studies have addressed the role of chaperome members in isolation, yet little is known about their relationships regarding how they interact and function together in malignancy. As function is probably highly dependent on endogenous conditions found in native tumours, chaperomes have resisted investigation, mainly due to the limitations of methods needed to disrupt or engineer the cellular environment to facilitate analysis. Such limitations have led to a bottleneck in our understanding of chaperome-related disease biology and in the development of chaperome-targeted cancer treatment. Here we examined the chaperome complexes in a large set of tumour specimens. The methods used maintained the endogenous native state of tumours and we exploited this to investigate the molecular characteristics and composition of the chaperome in cancer, the molecular factors that drive chaperome networks to crosstalk in tumours, the distinguishing factors of the chaperome in tumours sensitive to pharmacologic inhibition, and the characteristics of tumours that may benefit from chaperome therapy. We find that under conditions of stress, such as malignant transformation fuelled by MYC, the chaperome becomes biochemically 'rewired' to form a network of stable, survival-facilitating, high-molecular-weight complexes. The chaperones heat shock protein 90 (HSP90) and heat shock cognate protein 70 (HSC70) are nucleating sites for these physically and functionally integrated complexes. The results indicate that these tightly integrated chaperome units, here termed the epichaperome, can function as a network to enhance cellular survival, irrespective of tissue of origin or genetic background. The epichaperome, present in over half of all cancers tested, has implications for diagnostics and also provides potential vulnerability as a target for drug intervention.


Asunto(s)
Chaperonas Moleculares/metabolismo , Complejos Multiproteicos/metabolismo , Neoplasias/metabolismo , Neoplasias/patología , Animales , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Supervivencia Celular/genética , Descubrimiento de Drogas , Femenino , Genes myc/genética , Proteínas HSP70 de Choque Térmico/metabolismo , Proteínas HSP90 de Choque Térmico/metabolismo , Humanos , Ratones , Chaperonas Moleculares/antagonistas & inhibidores , Complejos Multiproteicos/antagonistas & inhibidores , Complejos Multiproteicos/química , Neoplasias/tratamiento farmacológico , Neoplasias/genética , Especificidad de Órganos
14.
Sensors (Basel) ; 22(15)2022 Aug 07.
Artículo en Inglés | MEDLINE | ID: mdl-35957458

RESUMEN

In this research, a microfluid-based extended gate field-effect transistor (EGFET) biosensor with an on-chip sensing window (OCSW) was fabricated. The detection window was composed of six metal layers, and a ruthenium dioxide (RuO2) film was spattered on the surface and functionalized with lactase to detect lactic acid (LA). To detect LA in a more diversified way, a microfluidic system was integrated with the biosensor. Moreover, a special package was used to seal the sensing window and microfluidic tube and insulate it from other parts to prevent water molecule invasion and chip damage. The sensitivity analysis of the EGFET biosensor was studied by a semiconductor parameter analyzer (SPA). The static and dynamic measurements of the EGFET with sensing windows on a chip were analyzed. The sensing characteristics of the EGFET biosensor were verified by the experimental results. The proposed biosensor is suitable for wearable applications due to the advantages of its low weight, low voltage, and simple manufacturing process.


Asunto(s)
Técnicas Biosensibles , Microfluídica , Técnicas Biosensibles/métodos , Ácido Láctico
15.
J Neurochem ; 159(6): 958-979, 2021 12.
Artículo en Inglés | MEDLINE | ID: mdl-34657288

RESUMEN

Adaptation to acute and chronic stress and/or persistent stressors is a subject of wide interest in central nervous system disorders. In this context, stress is an effector of change in organismal homeostasis and the response is generated when the brain perceives a potential threat. Herein, we discuss a nuanced and granular view whereby a wide variety of genotoxic and environmental stressors, including aging, genetic risk factors, environmental exposures, and age- and lifestyle-related changes, act as direct insults to cellular, as opposed to organismal, homeostasis. These two concepts of how stressors impact the central nervous system are not mutually exclusive. We discuss how maladaptive stressor-induced changes in protein connectivity through epichaperomes, disease-associated pathologic scaffolds composed of tightly bound chaperones, co-chaperones, and other factors, impact intracellular protein functionality altering phenotypes, that in turn disrupt and remodel brain networks ranging from intercellular to brain connectome levels. We provide an evidence-based view on how these maladaptive changes ranging from stressor to phenotype provide unique precision medicine opportunities for diagnostic and therapeutic development, especially in the context of neurodegenerative disorders including Alzheimer's disease where treatment options are currently limited.


Asunto(s)
Envejecimiento/metabolismo , Encéfalo/metabolismo , Exposición a Riesgos Ambientales/efectos adversos , Chaperonas Moleculares/metabolismo , Enfermedades Neurodegenerativas/metabolismo , Plasticidad Neuronal/fisiología , Adaptación Fisiológica/fisiología , Envejecimiento/patología , Animales , Encéfalo/patología , Chaperonina 60/metabolismo , Respuesta al Choque Térmico/fisiología , Homeostasis/fisiología , Humanos , Enfermedades Neurodegenerativas/patología , Estrés Oxidativo/fisiología
16.
J Thromb Thrombolysis ; 52(1): 232-238, 2021 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-33661478

RESUMEN

Limited information is available about use of direct oral anticoagulants (DOACs) in lung transplant recipients (LTRs). The purpose of this study is to describe the indications and use of long-term anticoagulation, including the safety and tolerability of DOACs, in LTRs. This was a single-center retrospective study. LTRs who received therapeutic anticoagulation were identified. Patient characteristics, indications for treatment, and complications of therapy were obtained. A total of 203 patients underwent lung transplantation of which 118 patients (58.1%) had an indication for anticoagulation. Patients with an indication for anticoagulation were older than those without (59 ± 14 years versus 48 ± 17 years, p < 0.001) and were more likely to be male (72.0% versus 50.6%, p = 0.002). Of the patients with indication for anticoagulation, 74 (62.7%) received it. Fifty-one (68.9%) of patients receiving anticoagulation were treated with DOACs. In the patients receiving anticoagulation, there were 14 major bleeding events in 13 patients, of which 3 were receiving DOACs and the remainder were receiving heparin or warfarin. The need for anticoagulation is common in LTRs for both atrial arrhythmias and venous thromboembolism. However, many patients with atrial arrhythmias do not receive anticoagulation. The use of DOACs is well tolerated and safe in LTRs.


Asunto(s)
Fibrilación Atrial , Receptores de Trasplantes , Administración Oral , Anticoagulantes/efectos adversos , Fibrilación Atrial/tratamiento farmacológico , Femenino , Humanos , Pulmón , Masculino , Estudios Retrospectivos , Warfarina/uso terapéutico
17.
J Biol Chem ; 294(6): 2162-2179, 2019 02 08.
Artículo en Inglés | MEDLINE | ID: mdl-30409908

RESUMEN

The chaperome is the collection of proteins in the cell that carry out molecular chaperoning functions. Changes in the interaction strength between chaperome proteins lead to an assembly that is functionally and structurally distinct from each constituent member. In this review, we discuss the epichaperome, the cellular network that forms when the chaperome components of distinct chaperome machineries come together as stable, functionally integrated, multimeric complexes. In tumors, maintenance of the epichaperome network is vital for tumor survival, rendering them vulnerable to therapeutic interventions that target critical epichaperome network components. We discuss how the epichaperome empowers an approach for precision medicine cancer trials where a new target, biomarker, and relevant drug candidates can be correlated and integrated. We introduce chemical biology methods to investigate the heterogeneity of the chaperome in a given cellular context. Lastly, we discuss how ligand-protein binding kinetics are more appropriate than equilibrium binding parameters to characterize and unravel chaperome targeting in cancer and to gauge the selectivity of ligands for specific tumor-associated chaperome pools.


Asunto(s)
Antineoplásicos , Sistemas de Liberación de Medicamentos/métodos , Chaperonas Moleculares , Proteínas de Neoplasias , Neoplasias , Mapas de Interacción de Proteínas/efectos de los fármacos , Animales , Antineoplásicos/química , Antineoplásicos/farmacocinética , Antineoplásicos/uso terapéutico , Humanos , Chaperonas Moleculares/antagonistas & inhibidores , Chaperonas Moleculares/metabolismo , Proteínas de Neoplasias/antagonistas & inhibidores , Proteínas de Neoplasias/metabolismo , Neoplasias/tratamiento farmacológico , Neoplasias/metabolismo , Neoplasias/patología
18.
BMC Evol Biol ; 20(1): 151, 2020 11 12.
Artículo en Inglés | MEDLINE | ID: mdl-33183225

RESUMEN

BACKGROUND: The northeastern part of the Qinghai-Tibet Plateau (QTP) presents a high number of plateau loach species. As one of the three major groups of fishes distributed on the QTP, plateau loach has high ecological value. However, the taxonomy and systematics of these fish are still controversial, and a large number of new species have been reported. The reason for this phenomenon is that the degree of morphological variation is low, the phylogenetic information provided by morphological and anatomical features used for species identification is relatively poor, and many cryptic species are observed. Based on the high-density sampling points from the biodiversity hotspots surveyed, this study aims to evaluate the biodiversity of plateau loach in the northeastern part of the QTP and reveal the hidden diversity by comparing morphological species with molecular operational taxonomic units (MOTUs). RESULTS: After careful identification and comparison of the morphology and DNA barcoding of 1630 specimens, 22 species were identified, with 20 considered valid local species and two identified as new species that had not been previously described. Based on the combination of morphological and molecular methods, a total of 24 native species were found, two of which were cryptic species: Triplophysa robusta sp1 and Triplophysa minxianensis sp1. Fourteen of the 24 species form clusters of barcodes that allow them to be reliably identified. The remaining cases involved 10 closely related species, including rapidly differentiated species and species that seemed to have experienced incomplete lineage sorting or showed introgressions. CONCLUSIONS: The results highlight the need to combine traditional taxonomies with molecular methods to correctly identify species, especially closely related species, such as the plateau loach. This study provides a basis for protecting the biodiversity of plateau loach.


Asunto(s)
Cipriniformes , Código de Barras del ADN Taxonómico , Filogenia , Animales , Cipriniformes/genética , ADN , Tibet
19.
Opt Express ; 28(7): 10350-10362, 2020 Mar 30.
Artículo en Inglés | MEDLINE | ID: mdl-32225622

RESUMEN

We design and fabricate a series of broadband silicon arbitrary power splitters with various split ratios using shortcuts to adiabaticity. In this approach, the system evolution is designed using the decoupled system states, and the desired split ratios are guaranteed by the boundary conditions. Furthermore, the system evolutions are optimized to be as close to the adiabatic states as possible, thus enhancing the robustness to wavelength and fabrication variations. The devices are more compact then the conventional adiabatic designs. Fabricated devices show broadband response for a wide wavelength range from 1.47 to 1.62 µm and also have excellent robustness against fabrication errors across an 8-inch wafer.

20.
Opt Lett ; 45(20): 5848-5851, 2020 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-33057300

RESUMEN

We report the first fast switchable multiwavelength optical parametric oscillator based on aperiodic optical superlattice technology. The constructed aperiodically poled lithium niobate (APPLN) integrates the functionalities of two quasi-phase-matching devices on a chip to work simultaneously as an electro-optic (EO) switchable notch-like filter and a multiline optical parametric downconverter. When such an APPLN is built in a 1064-nm-pumped optical resonator system, we achieve the oscillation of dual signals at 1540 and 1550 nm, for a single signal at 1540 nm, and a single signal at 1550 nm in the system when the 3-cm-long APPLN is driven by 0 V, 354 V, and 805 V, respectively. The switching among the three signal spectra is operationally simple and electro-optically fast. The electro-optically switched signals also feature enhanced power spectral density due to the unique EO gain-spectrum filtering mechanism employed in this work.

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