RESUMEN
The growing appreciation of immune cell-cell interactions within disease environments has led to extensive efforts to develop immunotherapies. However, characterizing complex cell-cell interfaces in high resolution remains challenging. Thus, technologies leveraging therapeutic-based modalities to profile intercellular environments offer opportunities to study cell-cell interactions with molecular-level insight. We introduce photocatalytic cell tagging (PhoTag) for interrogating cell-cell interactions using single-domain antibodies (VHHs) conjugated to photoactivatable flavin-based cofactors. Following irradiation with visible light, the flavin photocatalyst generates phenoxy radical tags for targeted labeling. Using this technology, we demonstrate selective synaptic labeling across the PD-1/PD-L1 axis in antigen-presenting cell-T cell systems. In combination with multiomics single-cell sequencing, we monitored interactions between peripheral blood mononuclear cells and Raji PD-L1 B cells, revealing differences in transient interactions with specific T cell subtypes. The utility of PhoTag in capturing cell-cell interactions will enable detailed profiling of intercellular communication across different biological systems.
Asunto(s)
Antígeno B7-H1 , Leucocitos Mononucleares , Comunicación Celular , Flavinas , InmunoterapiaRESUMEN
Lactobacillus kefir alcohol dehydrogenase (LkADH) and ketoreductase from Chryseobacterium sp. CA49 (ChKRED12) exhibit different chemoselectivity and stereoselectivity toward a substrate with both keto and aldehyde carbonyl groups. LkADH selectively reduces the keto carbonyl group while retaining the aldehyde carbonyl group, producing optically pure R-alcohols. In contrast, ChKRED12 selectively reduces the aldehyde group and exhibits low reactivity toward ketone carbonyls. This study investigated the structural basis for these differences and the role of specific residues in the active site. Molecular dynamics (MD) simulations and quantum chemical calculations were used to investigate the interactions between the substrate and the enzymes and the essential cause of this phenomenon. The present study has revealed that LkADH and ChKRED12 exhibit significant differences in the structure of their respective active pockets, which is a crucial determinant of their distinct chemoselectivity toward the same substrate. Moreover, residues N89, N113, and E144 within LkADH as well as Q151 and D190 within ChKRED12 have been identified as key contributors to substrate stabilization within the active pocket through electrostatic interactions and van der Waals forces, followed by hydride transfer utilizing the coenzyme NADPH. Furthermore, the enantioselectivity mechanism of LkADH has been elucidated using quantum chemical methods. Overall, these findings not only provide fundamental insights into the underlying reasons for the observed differences in selectivity but also offer a detailed mechanistic understanding of the catalytic reaction.
Asunto(s)
Aldehídos , Cetonas , Simulación de Dinámica Molecular , Cetonas/química , Cetonas/metabolismo , Aldehídos/química , Aldehídos/metabolismo , Especificidad por Sustrato , Teoría Cuántica , Lactobacillus/enzimología , Lactobacillus/metabolismo , Dominio Catalítico , Alcohol Deshidrogenasa/metabolismo , Alcohol Deshidrogenasa/químicaRESUMEN
'Cell Painting' is an imaging-based high-throughput phenotypic profiling (HTPP) method in which cultured cells are fluorescently labeled to visualize subcellular structures (i.e., nucleus, nucleoli, endoplasmic reticulum, cytoskeleton, Golgi apparatus / plasma membrane and mitochondria) and to quantify morphological changes in response to chemicals or other perturbagens. HTPP is a high-throughput and cost-effective bioactivity screening method that detects effects associated with many different molecular mechanisms in an untargeted manner, enabling rapid in vitro hazard assessment for thousands of chemicals. Here, 1201 chemicals from the ToxCast library were screened in concentration-response up to â¼100 µM in human U-2 OS cells using HTPP. A phenotype altering concentration (PAC) was estimated for chemicals active in the tested range. PACs tended to be higher than lower bound potency values estimated from a broad collection of targeted high-throughput assays, but lower than the threshold for cytotoxicity. In vitro to in vivo extrapolation (IVIVE) was used to estimate administered equivalent doses (AEDs) based on PACs for comparison to human exposure predictions. AEDs for 18/412 chemicals overlapped with predicted human exposures. Phenotypic profile information was also leveraged to identify putative mechanisms of action and group chemicals. Of 58 known nuclear receptor modulators, only glucocorticoids and retinoids produced characteristic profiles; and both receptor types are expressed in U-2 OS cells. Thirteen chemicals with profile similarity to glucocorticoids were tested in a secondary screen and one chemical, pyrene, was confirmed by an orthogonal gene expression assay as a novel putative GR modulating chemical. Most active chemicals demonstrated profiles not associated with a known mechanism-of-action. However, many structurally related chemicals produced similar profiles, with exceptions such as diniconazole, whose profile differed from other active conazoles. Overall, the present study demonstrates how HTPP can be applied in screening-level chemical assessments through a series of examples and brief case studies.
Asunto(s)
Bioensayo , Ensayos Analíticos de Alto Rendimiento , Humanos , Medición de Riesgo/métodos , Ensayos Analíticos de Alto Rendimiento/métodos , Células Cultivadas , Bioensayo/métodosRESUMEN
BACKGROUND: To study the role of computed tomography (CT)-derived radiomics features and clinical characteristics on the prognosis of "driver gene-negative" lung adenocarcinoma (LUAD) and to explore the potential molecular biological which may be helpful for patients' individual postoperative care. METHODS: A total of 180 patients with stage I-III "driver gene-negative" LUAD in the First Affiliated Hospital of Sun Yat-Sen University from September 2003 to June 2015 were retrospectively collected. The Least Absolute Shrinkage and Selection Operator (LASSO) Cox regression model was used to screen radiomics features and calculated the Rad-score. The prediction performance of the nomogram model based on radiomics features and clinical characteristics was validated and then assessed with respect to calibration. Gene set enrichment analysis (GSEA) was used to explore the relevant biological pathways. RESULTS: The radiomics and the clinicopathological characteristics were combined to construct a nomogram resulted in better performance for the estimation of OS (C-index: 0.815; 95% confidence interval [CI]: 0.756-0.874) than the clinicopathological nomogram (C-index: 0.765; 95% CI: 0.692-0.837). Decision curve analysis demonstrated that in terms of clinical usefulness, the radiomics nomogram outperformed the traditional staging system and the clinicopathological nomogram. The clinical prognostic risk score of each patient was calculated based on the radiomics nomogram and divided by X-tile into high-risk (> 65.28) and low-risk (≤ 65.28) groups. GSEA results showed that the low-risk score group was directly related to amino acid metabolism, and the high-risk score group was related to immune and metabolism pathways. CONCLUSIONS: The radiomics nomogram was promising to predict the prognosis of patients with "driver gene-negative" LUAD. The metabolism and immune-related pathways may provide new treatment orientation for this genetically unique subset of patients, which may serve as a potential tool to guide individual postoperative care for those patients.
Asunto(s)
Adenocarcinoma del Pulmón , Neoplasias Pulmonares , Humanos , Nomogramas , Estudios Retrospectivos , Adenocarcinoma del Pulmón/diagnóstico por imagen , Adenocarcinoma del Pulmón/genética , Adenocarcinoma del Pulmón/patología , Pronóstico , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologíaRESUMEN
Tertiary lymphoid structure (TLS) represents lymphocyte clusters in non-lymphoid organs. The formation and maintenance of TLS are dependent on follicular helper T (TFH) cells. However, the role of TFH cells during renal TLS formation and the renal fibrotic process has not been comprehensively elucidated in chronic kidney disease. Here, we detected the circulating TFH cells from 57 IgAN patients and found that the frequency of TFH cells was increased in IgA nephropathy patients with renal TLS and also increased in renal tissues from the ischemic-reperfusion-injury (IRI)-induced TLS model. The inducible T-cell co-stimulator (ICOS) is one of the surface marker molecules of TFH. Remarkably, the application of an ICOS-neutralizing antibody effectively prevented the upregulation of TFH cells and expression of its canonical functional mediator IL-21, and also reduced renal TLS formation and renal fibrosis in IRI mice in vivo. In the study of this mechanism, we found that recombinant IL-21 could directly promote renal fibrosis and the expression of p65. Furthermore, BAY 11-7085, a p65 selective inhibitor, could effectively alleviate the profibrotic effect induced by IL-21 stimulation. Our results together suggested that TFH cells contribute to TLS formation and renal fibrosis by IL-21. Targeting the ICOS-signaling pathway network could reduce TFH cell infiltration and alleviate renal fibrosis.
Asunto(s)
Glomerulonefritis por IGA , Estructuras Linfoides Terciarias , Animales , Ratones , Células T Auxiliares Foliculares , Interleucinas , Proteína Coestimuladora de Linfocitos T InduciblesRESUMEN
Switchgrass (Panicum virgatum L.) is an important perennial C4 species due to its large potential for cellulosic bioenergy feedstock production. Identification of quantitative trait loci (QTL) controlling important developmental traits is valuable to understanding the genetic basis and using marker-assisted selection (MAS) in switchgrass breeding. One F1 hybrid population derived from NL94 (â) × SL93 (â) and one S1 (first-generation selfed) population from NL94 were used in this study. Both the populations showed significant variations for genotype and genotype by environment interactions for three traits studied: plant vigor, spring green-up, and plant biomass. Plant vigor had strong and positive correlations with plant biomass in both populations. Broad-sense heritability estimates for plant vigor ranged from 0.46 to 0.74 and 0.45 to 0.74 in the hybrid and selfed population, respectively. Spring green-up had similar heritability estimates, 0.42-0.78 in the hybrid population, and 0.47-0.82 in the selfed population. Heritability of plant biomass was 0.54-0.64 in the hybrid population and 0.64-0.74 in the selfed population. Fifteen QTLs for spring green-up, 6 QTLs for plant vigor, and 3 QTLs for biomass yield were detected in the hybrid population, whereas 4 QTLs for spring green-up, 4 QTLs for plant vigor, and 1 QTL for biomass yield were detected in the selfed population. Markers associated with these QTLs can be used in MAS to accelerate switchgrass breeding program. This study provided new information in understanding the genetic control of biomass components and demonstrated substantial heterotic vigor that could be explored for breeding hybrid cultivars in switchgrass. Supplementary Information: The online version contains supplementary material available at 10.1007/s11032-022-01296-7.
RESUMEN
OBJECTIVE: The long-term safety of consuming low-carbohydrate diets (LCDs) remains controversial. As high protein and high fat might accelerate chronic kidney disease (CKD) progression, the impact of LCD on mortality might be different in subjects with CKD and subjects without CKD. Therefore, the objective of this study was to assess the association of LCD with mortality among individuals with and without CKD. METHODS: Data from 1158 subjects with CKD and 9523 subjects without CKD in the Third National Health and Nutrition Examination Survey were analyzed. The LCD score was calculated based on a 24-hour dietary recall interview. Mortality was from baseline until 31 December 2015. Cox proportional hazards regression models were fitted to estimate multivariable-adjusted hazard ratios and 95% confidence intervals. RESULTS: During the median follow-up of 24 years, 751 (65%) deaths and 2624 (28%) deaths were recorded in the CKD group and the non-CKD group, respectively. The multivariable-adjusted hazard ratio for all-cause mortality comparing the highest versus lowest quarters of LCD score was 1.51 (95% confidence interval, 1.01-2.25, P for trend = 0.045) in the CKD group. However, there were no association between the LCD score and all-cause mortality in the non-CKD group. CONCLUSIONS: The LCD scores were found significantly positively associated with all-cause mortality in adults with CKD, but not in adults without CKD.
Asunto(s)
Dieta Baja en Carbohidratos , Insuficiencia Renal Crónica , Adulto , Carbohidratos , Dieta Baja en Carbohidratos/métodos , Femenino , Humanos , Masculino , Encuestas Nutricionales , Encuestas y CuestionariosRESUMEN
OBJECTIVES: To develop and validate a radiomics model for evaluating treatment response to immune-checkpoint inhibitor plus chemotherapy (ICI + CT) in patients with advanced esophageal squamous cell carcinoma (ESCC). METHODS: A total of 64 patients with advance ESCC receiving first-line ICI + CT at two centers between January 2019 and June 2020 were enrolled in this study. Both 2D ROIs and 3D ROIs were segmented. ComBat correction was applied to minimize the potential bias on the results due to different scan protocols. A total of 788 features were extracted and radiomics models were built on corrected/uncorrected 2D and 3D features by using 5-fold cross-validation. The performance of the radiomics models was assessed by its discrimination, calibration and clinical usefulness with independent validation. RESULTS: Five features and support vector machine algorithm were selected to build the 2D uncorrected, 2D corrected, 3D uncorrected and 3D corrected radiomics models. The 2D radiomics models significantly outperformed the 3D radiomics models in both primary and validation cohorts. When ComBat correction was used, the performance of 2D models was better (p = 0.0059) in the training cohort, and significantly better (p < 0.0001) in the validation cohort. The 2D corrected radiomics model yielded the optimal performance and was used to build the nomogram. The calibration curve of the radiomics model demonstrated good agreement between prediction and observation and the decision curve analysis confirmed the clinical utility. CONCLUSIONS: The easy-to-use 2D corrected radiomics model could facilitate noninvasive preselection of ESCC patients who would benefit from ICI + CT.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Esofágicas/diagnóstico por imagen , Carcinoma de Células Escamosas de Esófago/diagnóstico por imagen , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Máquina de Vectores de Soporte , Anticuerpos Monoclonales Humanizados/administración & dosificación , Sesgo , Biomarcadores de Tumor , Carboplatino/administración & dosificación , Terapia Combinada/métodos , Docetaxel/administración & dosificación , Neoplasias Esofágicas/tratamiento farmacológico , Neoplasias Esofágicas/patología , Carcinoma de Células Escamosas de Esófago/tratamiento farmacológico , Carcinoma de Células Escamosas de Esófago/patología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Nomogramas , Tomografía Computarizada por Rayos X/métodos , Resultado del TratamientoRESUMEN
INTRODUCTION: Increasing evidence has demonstrated that loss of peritubular capillaries plays a critical role in renal interstitial fibrosis. Leucine-rich α2-glycoprotein-1 (LRG1) has been observed promoting angiogenesis in the ocular disease mouse model and myocardial infarction model. We aimed to explore the role of LRG1 in renal interstitial fibrosis. METHODS: We analyzed the expression of LRG1 in the plasma and kidney of CKD patients by ELISA and immunohistochemistry. Relationships between the expression of LRG1 in plasma and kidney and renal fibrosis and inflammation were analyzed. Tube formation assay was used to detect the angiogenesis in the human umbilical vein endothelial cell lines (HUVECs). And real-time PCR was used to detect the mRNA expression of LRG1, inflammatory factors, renal tubular injury indicators, pro-fibrotic cytokines, and CD31. We examined the effects of genetic ablation of LRG1 on renal fibrosis induced by unilateral ureteral obstruction (UUO) mice model at day 7. RESULTS: We demonstrated that the expression of LRG1 in renal tissues and plasma samples was upregulated in CKD patients. And the expression of LRG1 was elevated in human renal tubular epithelial cell line (HK-2) cells in response to the stimulation of TNF-α in vitro, and in kidney after UUO in vivo. The deficiency of the LRG1 gene aggravated renal fibrosis, inflammatory cells infiltration, and capillary rarefaction after UUO. In vitro, LRG1 promoted the tube formation of HUVEC cells. LRG1 inhibits fibronectin secretion induced by TGF-ß1 in HK-2 and overexpression of LRG1 in HK-2 cells decreased fibronectin secretion. CONCLUSION: LRG1 may prevent renal fibrosis by inhibiting the secretion of inflammatory and pro-fibrotic cytokines and promoting angiogenesis.
Asunto(s)
Citocinas/fisiología , Glicoproteínas/fisiología , Enfermedades Renales/etiología , Riñón/patología , Rarefacción Microvascular/etiología , Adulto , Animales , Femenino , Fibrosis/etiología , Humanos , Masculino , Ratones , Persona de Mediana EdadRESUMEN
A three-component reaction has been developed for the construction of multiaryl-substituted pyrrole derivatives from arylketones, amines, and nitrovinylarenes under metal-free conditions. Hence, homologous 1,2,4-triaryl-substituted pyrrole products were obtained in good to high yields. Furthermore, 2,3,5-triaryl-substituted pyrroles were selectively formed in the absence of nitrovinylarenes. The photophysical properties of some pyrrole products have been investigated to show good aggregation-induced emission (AIE) activity.
RESUMEN
A multifunctional sensing platform based on bright blue-fluorescent nitrogen-doped carbon dots (N-CDs) has been ingeniously designed for the sensitive determination of Hg2+ and pH. The N-CDs were facilely fabricated via a one-step hydrothermal treatment of citric acid and folic acid with admirable merits including exceptional stability, low toxicity and distinguished biocompatibility. Intriguingly, the obtained N-CDs can be utilized to detect Hg2+ on the basis of the dynamic quenching effect, showing a linear range of 0 µM-400 µM as well as a detection limit of 0.124 µM. In addition, the obtained N-CDs revealed a significant emission enhancement with increasing pH from 4.0 to 10.0 and acquired a good linearity in the pH range of 6.8-7.8. Taking advantage of efficient analysis of Hg2+ and pH in aqueous solution, the as-synthesized N-CDs have been extended to the visualization biosensing platform to timely track Hg2+ and pH in living cells.
Asunto(s)
Mercurio , Puntos Cuánticos , Carbono , Concentración de Iones de Hidrógeno , Mercurio/análisis , Mercurio/química , NitrógenoRESUMEN
Natural products represent a rich reservoir of small molecule drug candidates utilized as antimicrobial drugs, anticancer therapies, and immunomodulatory agents. These molecules are microbial secondary metabolites synthesized by co-localized genes termed Biosynthetic Gene Clusters (BGCs). The increase in full microbial genomes and similar resources has led to development of BGC prediction algorithms, although their precision and ability to identify novel BGC classes could be improved. Here we present a deep learning strategy (DeepBGC) that offers reduced false positive rates in BGC identification and an improved ability to extrapolate and identify novel BGC classes compared to existing machine-learning tools. We supplemented this with random forest classifiers that accurately predicted BGC product classes and potential chemical activity. Application of DeepBGC to bacterial genomes uncovered previously undetectable putative BGCs that may code for natural products with novel biologic activities. The improved accuracy and classification ability of DeepBGC represents a major addition to in-silico BGC identification.
Asunto(s)
Vías Biosintéticas/genética , Biología Computacional/métodos , Minería de Datos/métodos , Familia de Multigenes/genética , Aprendizaje Profundo , Genoma , Genoma Bacteriano/genéticaRESUMEN
Cancer cell stemness results in the occurrence and progression of tumors and Oct4 (octamer-binding transcription factor) has been confirmed to be a critical contributor and marker of cancer cell stemness. Here, we aimed to explore the underlying mechanisms contributing to Oct4 protein stability, which is necessary for thyroid cancer (TC) cell stemness. We indicated that carboxy terminus of HSP70-interacting protein (CHIP) protein was lowly expressed in TC tissues and cells, and positively correlated with the overall survival of TC patients. By analyzing the co-expression network in TC tissues, we found that CHIP and Oct4 expression exhibited a negative correlation. Functional experiments showed that CHIP knockdown promoted the stemness of TC cells, while CHIP overexpression reduced the stemness of TC spheroids formed by TC cells, in which CHIP expression was significantly decreased. Furthermore, CHIP had no effect on TC cell viability. Mechanistic studies revealed that CHIP directly interacted with Oct4 protein and induced Oct4 ubiquitination, whereas a catalytic CHIP mutant (H260Q) did not. And CHIP regulated the stemness of TC cells in an Oct4-dependent manner. Overall, this work indicates that the CHIP/Oct4 axis is essential for TC cell stemness.
Asunto(s)
Proliferación Celular , Células Madre Neoplásicas/metabolismo , Factor 3 de Transcripción de Unión a Octámeros/genética , Neoplasias de la Tiroides/patología , Ubiquitina-Proteína Ligasas/genética , Línea Celular Tumoral , Proliferación Celular/genética , Supervivencia Celular/genética , Regulación Neoplásica de la Expresión Génica , Técnicas de Silenciamiento del Gen , Humanos , Masculino , Células Madre Neoplásicas/patología , Factor 3 de Transcripción de Unión a Octámeros/metabolismo , Estabilidad Proteica , Neoplasias de la Tiroides/genética , Neoplasias de la Tiroides/metabolismo , Ubiquitina-Proteína Ligasas/metabolismo , UbiquitinaciónRESUMEN
Background and objectives: Unhealthy, physically inactive lifestyles increase the risk of future cardiovascular events and impaired physical fitness in individuals with schizophrenia. Insufficient literature exists to provide fundamental information about appropriate exercise training modality for this population. This pilot study preliminarily investigated the effects of a 12-week moderate-intensity bench-step exercise training (BSET) program on cardiopulmonary fitness, mood state, and cognition in patients with schizophrenia. Methods: Twenty-eight patients with schizophrenia completed this study. The participants were allocated into either bench-step exercise-training (BSET; N = 14) or control (CTRL; N = 14) groups according to their preferences. The BSET group received a 12-week bench-step intervention, whereas the CTRL group did not participate in any training. The Beck Depression Inventory-II (BDI-II), 6-min walk test (6MWD), and Symbol Digit Modalities Test (SDMT) were assessed at baseline (PRE) and at the end of the intervention (POST) to determine mood state, endurance fitness, and attention, respectively. Results: After a 12-week BSET intervention, the 6MWD was significantly increased in the BSET (p = 0.007) but not in the CTRL (p > 0.05). The participants with BSET intervention showed a significant decrease in BDI-II at the end of the intervention (p = 0.03). However, SDMT scores were not different in both BSET and CTRL (p > 0.05). Conclusions: This study demonstrated that the 12-week intervention of moderate-intensity bench-step exercise training (frequency: 1 session/week; each session of 30 min; step cadence: 96 beats/min) might effectively enhance cardiopulmonary fitness and mood state in patients with schizophrenia. However, attention did not change after the bench-step exercise intervention.
Asunto(s)
Esquizofrenia , Ejercicio Físico , Humanos , Aptitud Física , Proyectos Piloto , Esquizofrenia/terapiaRESUMEN
Bright blue fluorescent N-doped carbon dots (N-CDs) with satisfactory yield (54%) were successfully fabricated by one-step hydrothermal treatment of astragalus. The obtained N-CDs possessed superior stability, solubility and high resistance to photo bleaching, and can be used as label-free nanosensors for the determination of Fe3+. The quantitative analysis of Fe3+ showed a linear range of 50 to 250 µM with the detection limit as low as 42 nM. Moreover, the as-prepared N-CDs have been used in cellular imaging owing to their distinct merits of simplicity, convenience, fast response and good selectivity towards Fe3+. Besides, the N-CDs could also be further used as fluorescent inks for drawing luminescent patterns.
RESUMEN
Here, we report an environmentally friendly fabrication strategy of bright yellow fluorescent carbon dots (y-CDs) and construct a rapid and accurate multifunctional sensing platform for the effective detection of temperature and Cu2+. The y-CDs were favorably obtained through a one-step hydrothermal treatment of natural Smilax China for the first time and exhibit long-wavelength emission at 542 nm under an excitation wavelength of 470 nm. Additionally, the obtained y-CDs exhibit superior biocompatibility and distinguished stability under different conditions, and display a respectable fluorescence quantum yield of up to 22.37%. Appealingly, the as-prepared y-CDs were implemented as temperature probes within ranges of 25 °C-40 °C and 45 °C-80 °C. Significantly, based on the static quenching effect, the as-prepared y-CDs were developed as an effective platform for fluorescence sensing of Cu2+, with linear ranges of 0.5 µM-10 µM, 75 µM-225 µM and 250 µM-350 µM, achieving a detection limit of 28 nM. Furthermore, confocal fluorescence imaging of PC12 cells was achieved successfully, which indicated that the as-synthesized y-CDs could visualize Cu2+ fluctuations in living cells.
Asunto(s)
Cobre/análisis , Colorantes Fluorescentes/química , Puntos Cuánticos/química , Temperatura , Animales , Carbono/química , Carbono/toxicidad , Límite de Detección , Microscopía Confocal/métodos , Microscopía Fluorescente/métodos , Células PC12 , Puntos Cuánticos/toxicidad , Ratas , Smilax/química , Espectrometría de Fluorescencia/métodosRESUMEN
An efficient synthesis of pyrroles and indoles has been developed via three-component ordered annulation of amines, ketones, and nitrovinylarenes. The reaction selectivity can be well controlled under metal-free conditions to afford the corresponding heterocyclic products in good yields.
RESUMEN
The domestication of the horse â¼ 5.5 kya and the emergence of mounted riding, chariotry, and cavalry dramatically transformed human civilization. However, the genetics underlying horse domestication are difficult to reconstruct, given the near extinction of wild horses. We therefore sequenced two ancient horse genomes from Taymyr, Russia (at 7.4- and 24.3-fold coverage), both predating the earliest archeological evidence of domestication. We compared these genomes with genomes of domesticated horses and the wild Przewalski's horse and found genetic structure within Eurasia in the Late Pleistocene, with the ancient population contributing significantly to the genetic variation of domesticated breeds. We furthermore identified a conservative set of 125 potential domestication targets using four complementary scans for genes that have undergone positive selection. One group of genes is involved in muscular and limb development, articular junctions, and the cardiac system, and may represent physiological adaptations to human utilization. A second group consists of genes with cognitive functions, including social behavior, learning capabilities, fear response, and agreeableness, which may have been key for taming horses. We also found that domestication is associated with inbreeding and an excess of deleterious mutations. This genetic load is in line with the "cost of domestication" hypothesis also reported for rice, tomatoes, and dogs, and it is generally attributed to the relaxation of purifying selection resulting from the strong demographic bottlenecks accompanying domestication. Our work demonstrates the power of ancient genomes to reconstruct the complex genetic changes that transformed wild animals into their domesticated forms, and the population context in which this process took place.
Asunto(s)
Animales Domésticos/genética , Evolución Molecular , Genoma/fisiología , Caballos/genética , Animales , Sistema Cardiovascular/anatomía & histología , Perros , Miembro Posterior/anatomía & histología , Miembro Posterior/fisiología , Caballos/anatomía & histología , Humanos , Endogamia , Federación de RusiaRESUMEN
Soil dissolved organic matter (DOM) plays an important role in the biogeochemistry of carbon, nitrogen, and phosphorus and in the transport of heavy metals and pesticides in soil. In moisture soil, green manures and soils were sampled in situ at the ploughed stage of green manures. A 56-day laboratory incubation experiment was conducted to simulate the dynamic changes of soil DOM influenced by the decomposition of green manures, the green manures were Hairy vetch (Vicia villosa Roth.), February orchid (Orychophragmus Violaceus L.), Rye (Secale cereale L.), the soil without green manure was used as a control (CK). The composition and ultraviolet-visible spectrum parameters of soil DOM were investigated at different incubation stages. Results showed that green manures could increase the dissolved organic carbon (DOC), the total organic acids (TOAs) and total carbohydrate (TCs) contents, and all treatments were reached a peak on the 1st day and decreased later. Hairy vetch affected DOC and TOAs most and were increased by 114.01% and 109.10% higher than CK respectively at the 1st and 14th day. Rye influenced the total carbohydrate (TCs) most and was maximumly 323.18% higher than CK at the 42nd day. Green manures could increase the dissolved organic nitrogen (DON) content, DON in all green manure treatments increased on the 1st day, decreased several days later and increased again after 20ï½30 d. Hairy vetch effected DON best and was 305.83% higher than CK at the 42nd day. All green manures increased in SUVA254, SUVA260, SUVA272, SUVA280 and SAUC240-400, while decreasing in A250/A365 and A240/A420. The PCA analysis of ultraviolet-visible spectrum parameters showed that SUVA254, SUVA260, SUVA272, SUVA280 had a high positive correlation between each other, and the same situation was found between A250/A365 and A240/A420. Among them, SAUC240-400 was a key factor parameter featuring the characteristics of DOM. The results suggested that green manures could increase the contents of DOM and its aromaticity, hydrophobic percentage, humification degree and average molecular weight, and could be increased and the stability of DOM could be enhanced accordingly. The ultraviolet-visible spectrum parameters could indicate the changes of characteristics of DOM in this study.
Asunto(s)
Estiércol , Suelo , Ácidos , Carbono , China , Metales Pesados , Peso Molecular , Nitrógeno , Compuestos Orgánicos , FósforoRESUMEN
BACKGROUND: Venomous organisms serve as wonderful systems to study the evolution and expression of genes that are directly associated with prey capture. To evaluate the relationship between venom gene expression and prey utilization, we examined these features among individuals of different ages of the venomous, worm-eating marine snail Conus ebraeus. We determined expression levels of six genes that encode venom components, used a DNA-based approach to evaluate the identity of prey items, and compared patterns of venom gene expression and dietary specialization. RESULTS: C. ebraeus exhibits two major shifts in diet with age-an initial transition from a relatively broad dietary breadth to a narrower one and then a return to a broader diet. Venom gene expression patterns also change with growth. All six venom genes are up-regulated in small individuals, down-regulated in medium-sized individuals, and then either up-regulated or continued to be down-regulated in members of the largest size class. Venom gene expression is not significantly different among individuals consuming different types of prey, but instead is coupled and slightly delayed with shifts in prey diversity. CONCLUSION: These results imply that changes in gene expression contribute to intraspecific variation of venom composition and that gene expression patterns respond to changes in the diversity of food resources during different growth stages.