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GGC repeat expansion in the 5' untranslated region (UTR) of NOTCH2NLC is associated with a broad spectrum of neurological disorders, especially neuronal intranuclear inclusion disease (NIID). Studies have found that GGC repeat expansion in NOTCH2NLC induces the formation of polyglycine (polyG)-containing protein, which is involved in the formation of neuronal intranuclear inclusions. However, the mechanism of neurotoxicity induced by NOTCH2NLC GGC repeats is unclear. Here, we used NIID patient-specific induced pluripotent stem cell (iPSC)-derived 3D cerebral organoids (3DCOs) and cellular models to investigate the pathophysiological mechanisms of NOTCH2NLC GGC repeat expansion. IPSC-derived 3DCOs and cellular models showed the deposition of polyG-containing intranuclear inclusions. The NOTCH2NLC GGC repeats could induce the upregulation of autophagic flux, enhance integrated stress response and activate EIF2α phosphorylation. Bulk RNA sequencing for iPSC-derived neurons and single-cell RNA sequencing (scRNA-seq) for iPSC-derived 3DCOs revealed that NOTCH2NLC GGC repeats may be associated with dysfunctions in ribosome biogenesis and translation. Moreover, NOTCH2NLC GGC repeats could induce the NPM1 nucleoplasm translocation, increase nucleolar stress, impair ribosome biogenesis and induce ribosomal RNA sequestration, suggesting dysfunction of membraneless organelles in the NIID cellular model. Dysfunctions in ribosome biogenesis and phosphorylated EIF2α and the resulting increase in the formation of G3BP1-positive stress granules may together lead to whole-cell translational inhibition, which may eventually cause cell death. Interestingly, scRNA-seq revealed that NOTCH2NLC GGC repeats may be associated with a significantly decreased proportion of immature neurons while 3DCOs were developing. Together, our results underscore the value of patient-specific iPSC-derived 3DCOs in investigating the mechanisms of polyG diseases, especially those caused by repeats in human-specific genes.
Assuntos
DNA Helicases , RNA Helicases , Humanos , Proteínas de Ligação a Poli-ADP-Ribose , Proteínas com Motivo de Reconhecimento de RNA , Regiões 5' não Traduzidas , Corpos de Inclusão Intranuclear , Ribossomos , Expansão das Repetições de Trinucleotídeos/genéticaRESUMO
The implantation of human embryos is a complex process involving various cytokines and receptors expressed by both endometrium and embryos. However, the role of cytokines produced by a single embryo in successful implantation is largely unknown. This study aimed to investigate the role of IL-1ß expressed in a single-embryo-conditioned medium (ECM) in embryo implantation. Seventy samples of single ECM were analyzed by a specially designed magnetic-beads-based microfluidic chip from 15 women. We discovered that IL-1ß level increased as the embryo developed, and the difference was significant. In addition, receiver operator characteristic (ROC) curves analysis showed a higher chance of pregnancy when the IL-1ß level on day 5 ECM was below 79.37 pg/mL and the difference between day 5 and day 3 was below 24.90 pg/mL. Our study discovered a possible association between embryonic proteomic expression and successful implantation, which might facilitate single-embryo transfer in the future by helping clinicians identify the embryo with the greatest implantation potential.
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Microfluídica , Proteômica , Gravidez , Humanos , Feminino , Meios de Cultivo Condicionados , Interleucina-1beta , Blastocisto , Implantação do Embrião , CitocinasRESUMO
INTRODUCTION: We determined the prevalence of major depression and suicidal ideation, and the associated risk factors in a large sample of Chinese resident physicians. METHODS: This multi-center cross-sectional study was conducted from December 2019 to February 2020 and involved 1343 residents from eight centers. Extensive characteristics, including demographics, dietary habits, life-related factors, work-related factors, and psychological factors were collected based on a self-reported questionnaire. Specific scales measured the levels of sleep quality, physical activity, depression, perceived organization support, psychological capital, and burnout. Adjusted odds ratios and 95% confidence intervals were determined by binary paired logistic regression. RESULTS: Of the residents enrolled in the study, 12.90% suffered from major depression and 9.70% suffered from suicidal ideation. Four overlapped independent risk factors were identified for major depression and suicidal ideation: poor sleep quality (OR = 1.317, OR = 1.200); lower optimism of psychological capital (OR = 0.899, OR = 0.835); higher depersonalization, (OR = 1.086, OR = 1.097); and reduced personal accomplishment (OR = 0.963, OR = 0.962). The inappropriate working duration weekly (< 40 h vs. 40-60 h; OR = 2.812, > 60 h vs. 40-60 h; OR = 1.945), and higher emotional exhaustion (OR = 1.121) were the only risk factors for major depression. Higher hope of psychological capital (OR = 1.077) was only for suicidal ideation. CONCLUSION: This study revealed a substantial prevalence of major depression and suicidal ideation in Chinese residents, and identified several shared risk factors for major depression and suicidal ideation. These findings enrich the existing theoretical model of depression and demonstrated a critical need for additional studies that investigate intervention strategies that can address the mental health in residents. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR1900027707. Registered 24 Nov. 2019, http://www.chictr.org.cn/index.aspx.
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Transtorno Depressivo Maior , Internato e Residência , Humanos , Ideação Suicida , Estudos Transversais , Transtorno Depressivo Maior/epidemiologia , Transtorno Depressivo Maior/psicologia , Prevalência , Depressão/epidemiologia , Depressão/psicologia , Pontuação de Propensão , Fatores de RiscoRESUMO
Phytochemical investigation on the concentrate of Huangjing wine, resulted in the isolation of three new tyrosol derivatives 4'''-hydroxyphenethyl 2-(R)-hydroxy-3-phenylpropionate (1), 4'''-hydroxyphenethyl(4'-hydroxy-3'-methoxyphenyl)propionate (2) and 4''-hydroxyphenethyl ethyl succinate (3), together with 5 known compounds, ferulic acid (4), L-phenyllactic acid (5), hydroxytyrosol (6), dihydroferulic acid (7), cyclo(L-Pro-D-Tyr) (8). Their structures were elucidated using spectroscopic analysis and by comparison with the literature data. All compounds displayed antioxidant effect in the DPPH (2,2-diphenyl-1-picrylhydrazyl) radical. Among them, the new compound 2 exhibited obvious antioxidant effect, and new compounds 1 and 3 exhibited medium antioxidant effect.
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Vinho , Vinho/análise , Antioxidantes/farmacologia , Antioxidantes/química , Estrutura MolecularRESUMO
Microalgae that have recently captivated interest worldwide are a great source of renewable, sustainable and economical biofuels. The extensive potential application in the renewable energy, biopharmaceutical and nutraceutical industries have made them necessary resources for green energy. Microalgae can substitute liquid fossil fuels based on cost, renewability and environmental concern. Microfluidic-based systems outperform their competitors by executing many functions, such as sorting and analysing small volumes of samples (nanolitre to picolitre) with better sensitivities. In this review, we consider the developing uses of microfluidic technology on microalgal processes such as cell sorting, cultivation, harvesting and applications in biofuels and biosensing.
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Microalgas , Biocombustíveis , Biomassa , Combustíveis Fósseis , MicrofluídicaRESUMO
The clinical application of gentamicin may lead to acute kidney injury (AKI), and the nephrotoxicity of gentamicin is related to the pathological mechanism of several oxidative and inflammatory cytokines. Plant-derived essential oils have good anti-inflammatory and antioxidant properties. This study aimed to clarify the protective effect of Amomum tsao-ko essential oils (AOs) on gentamicin-induced AKI in rats and its possible mechanism. The rat AKI model was induced by intraperitoneal injection of gentamicin. After 14 days of oral AO treatment, the renal function and pathological changes of the kidney tissues were evaluated, and the level of kidney tissue oxidative stress was detected. The content of inflammatory cytokines was measured by ELISA. The expression of ERK1/2, JNK1/2, p38, NF-κB, caspase-3, and Bax/Bcl-2 proteins were estimated by Western blot analysis. The results showed that taking AO reduced the contents of serum urea and creatinine in AKI rats and improve the pathological changes and oxidative stress of the kidney tissue in rats. At the same time, AO reduced inflammation and apoptosis during AKI by regulating the MAPK pathway. The data show that AO has a protective effect on the kidneys and may be a potential drug for treating kidney injury.
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Injúria Renal Aguda , Amomum , Óleos Voláteis , Ratos , Animais , Gentamicinas/efeitos adversos , Caspase 3/metabolismo , Sistema de Sinalização das MAP Quinases , NF-kappa B/metabolismo , Creatinina , Antioxidantes/farmacologia , Proteína X Associada a bcl-2/metabolismo , Óleos Voláteis/uso terapêutico , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/tratamento farmacológico , Injúria Renal Aguda/patologia , Apoptose , Inflamação/metabolismo , Rim , Transdução de Sinais , Estresse Oxidativo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Citocinas/metabolismo , Anti-Inflamatórios/uso terapêutico , Ureia/farmacologiaRESUMO
BACKGROUND: LncRNA WT1-AS inhibits gastric cancer, while its role in other cancers is unknown. We investigated the role of WT1-AS in non-small cell lung cancer (NSCLC). METHODS: Sixty-six NSCLC patients (40 males and 26 females; 36 to 68 years old; mean age 52.7 ± 6.4 years old) were selected from the 178 NSCLC patients operated on for lung cancer between 2010 and 2013. RT-qPCR was used to analyze the expression of lncRNA. Overexpression experiments were performed to assess interactions between lncRNAs. CCK-8 assay was carried to evaluate the roles of WT1-AS and UCA1 in regulating cell proliferation. Cell invasion and migration assays were performed to assess the roles of WT1-AS and UCA1 in regulating cell invasion and migration. Western-blot was performed to illustrate the effect of WT1-AS and UCA1 in EMT. RESULTS: WT1-AS was downregulated in NSCLC and was correlated with poor survival. The expression of WT1-AS in NSCLC was not correlated with clinical stages. LncRNA UCA1 was upregulated in cancer tissues and inversely correlated with WT1-AS. Overexpression of UCA1 did not affect WT1-AS, while overexpression of WT1-AS led to inhibited expression of UCA1. Overexpression of UCA1 resulted in increased proliferation, EMT, migration and invasion of NSCLC cells, while overexpression of WT1-AS showed opposite effects. In addition, overexpression of UCA1 inhibited the role of overexpression of WT1-AS. CONCLUSIONS: Therefore, overexpression of WT1-AS may inhibit the cell proliferation and EMT to decrease cell migration and invasion of NSCLC cells by downregulating UCA1.
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Biomarcadores Tumorais/genética , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Regulação Neoplásica da Expressão Gênica , Neoplasias Pulmonares/mortalidade , RNA Longo não Codificante/genética , Adulto , Idoso , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Movimento Celular , Proliferação de Células , Feminino , Seguimentos , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Transdução de Sinais , Taxa de Sobrevida , Células Tumorais CultivadasRESUMO
Infertility is a state of the male or female reproductive system that is defined as the failure to achieve pregnancy even after 12 or more months of regular unprotected sexual intercourse. Assisted reproductive technology (ART) plays a crucial role in addressing infertility. Various ART are now available for infertile couples. Fertilization in vitro (IVF), intracytoplasmic sperm injection (ICSI) and intrauterine insemination (IUI) are the most common techniques in this regard. Various microfluidic technologies can incorporate various ART procedures such as embryo and gamete (sperm and oocyte) analysis, sorting, manipulation, culture and monitoring. Hence, this review intends to summarize the current knowledge about the application of this approach towards cell biology to enhance ART.
Assuntos
Inseminação Artificial Heteróloga , Técnicas Analíticas Microfluídicas , Injeções de Esperma Intracitoplásmicas , Feminino , Humanos , Microfluídica , GravidezRESUMO
PURPOSE: The efficacy and tolerability of adding chemotherapy to radiotherapy in the era of intensity-modulated radiation therapy (IMRT) remain controversial among older patients with nasopharyngeal carcinoma (NPC). The present study compared IMRT alone with IMRT in combination with chemotherapy in elderly NPC patients. METHODS: Between January 2011 and December 2014, 102 patients aged >65 years with NPC who received IMRT alone (IMRT group) or IMRT in combination with chemotherapy (IMRT/CT group) were enrolled. Patients from both treatment arms were pair-matched (1:1 ratio) based on six clinical factors. Differences in overall survival (OS), disease-free survival (DFS), locoregional relapse-free survival (LRRFS), and distant metastasis-free survival (DMFS) were assessed using the Kaplan-Meier method and Cox proportional hazards models, whereas the toxicity profile was assessed using Common Terminology Criteria for Adverse Events (CTCAE) version 4. RESULTS: No significant differences were noted in OS (72.1% vs. 72.5%, pâ¯= 0.799), DFS (65.9% vs. 70.1%, pâ¯= 0.733), LRRFS (76.4% vs. 71.6%, pâ¯= 0.184), and DMFS (90.8% vs. 98.0%, pâ¯= 0.610) between the IMRT and IMRT/CT groups. Multivariate analyses showed that chemotherapy was not an independent factor for OS, DFS, LRRFS, and DMFS. However, the incidences of grade 3 vomiting/nausea (pâ¯= 0.000), leukopenia/neutropenia (pâ¯= 0.000), thrombocytopenia (pâ¯= 0.041), and anemia (pâ¯= 0.040) were significantly higher in the IMRT/CT group compared with the IMRT group. No grade 4 toxicities were observed. CONCLUSION: IMRT alone was similar to IMRT/CT in treating elderly NPC patients (age >65 years), with comparable survival outcomes and less grade 3 toxicities.
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Quimiorradioterapia , Carcinoma Nasofaríngeo/terapia , Neoplasias Nasofaríngeas/terapia , Radioterapia de Intensidade Modulada , Idoso , Quimiorradioterapia/métodos , Intervalo Livre de Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Carcinoma Nasofaríngeo/patologia , Neoplasias Nasofaríngeas/patologia , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/prevenção & controle , Modelos de Riscos Proporcionais , Radioterapia de Intensidade Modulada/métodos , Estudos RetrospectivosRESUMO
The development of novel magnetic nanoparticles (MNPs) with satisfactory biocompatibility for biomedical applications has been the subject of extensive exploration over the past two decades. In this work, we synthesized superparamagnetic iron oxide MNPs coated with polystyrene sulfonic acid (PSS-MNPs) and with a conventional co-precipitation method. The core size and hydrodynamic diameter of the PSS-MNPs were determined as 8-18 nm and 50-200 nm with a transmission electron microscopy and dynamic light scattering, respectively. The saturation magnetization of the particles was measured as 60 emu g-1 with a superconducting quantum-interference-device magnetometer. The PSS content in the PSS-MNPs was 17% of the entire PSS-MNPs according to thermogravimetric analysis. Fourier-transform infrared spectra were recorded to detect the presence of SO3 - groups, which confirmed a successful PSS coating. The structural properties of the PSS-MNPs, including the crystalline lattice, composition and phases, were characterized with an X-ray powder diffractometer and 3D nanometer-scale Raman microspectrometer. MTT assay and Prussian-blue staining showed that, although PSS-MNPs caused no cytotoxicity in both NIH-3T3 mouse fibroblasts and SK-HEP1 human liver-cancer cells up to 1000 µg mL-1, SK-HEP1 cells exhibited significantly greater uptake of PSS-MNPs than NIH-3T3 cells. The low cytotoxicity and high biocompatibility of PSS-MNPs in human cancer cells demonstrated in the present work might have prospective applications for drug delivery.
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Understanding the effect of liposome size on tendency for accumulation in tumour tissue requires preparation of defined populations of different sized particles. However, controlling the size distributions without changing the lipid composition is difficult, and differences in compositions itself modify distribution behaviour. Here, a commercial microfluidic format as well as traditional methods was used to prepare doxorubicin-loaded liposomes of different size distributions but with the same lipid composition, and drug retention, biodistribution and localization in tumour tissues were evaluated. The small (â¼50 nm diameter) liposomes prepared by microfluidics and large (â¼75 nm diameter) liposomes displayed similar drug retention in in vitro release studies, and similar biodistribution patterns in tumour-bearing mice. However, the extent of extravasation was clearly dependent on size of the liposomes, with the small liposomes showing tissue distribution beyond the vascular area compared to the large liposomes. The use of microfluidics to prepare smaller size distribution liposomes compared to sonication methods is demonstrated, and allowed preparation of different size distribution drug carriers from the same lipid composition to enable new understanding of tissue distribution in compositionally consistent materials is demonstrated.
Assuntos
Antineoplásicos/administração & dosagem , Doxorrubicina/análogos & derivados , Sistemas de Liberação de Medicamentos , Lipossomos , Microfluídica , Animais , Transporte Biológico , Doxorrubicina/administração & dosagem , Liberação Controlada de Fármacos , Feminino , Lipossomos/química , Camundongos , Camundongos Endogâmicos BALB C , Neoplasias Experimentais/tratamento farmacológico , Tamanho da Partícula , Polietilenoglicóis/administração & dosagemRESUMO
To assure faithful chromosome segregation, cells make use of the spindle assembly checkpoint, which can be activated in aneuploid cancer cells. In this study, the efficacies of inhibiting polo-like kinase 1 (PLK1) on the radiosensitization of non-small-cell lung cancer (NSCLC) cells were studied. Clonogenic survival assay was performed to identify the effects of the PLK1 inhibitor on radiosensitivity within NSCLC cells. Mitotic catastrophe assessment was used to measure the cell death and histone H2AX protein (γH2AX) foci were utilized to assess the DNA double-strand breaks (DSB). The transcriptome was analyzed via unbiased profiling of microarray expression. The results showed that the postradiation mitotic catastrophe induction and the DSB repair were induced by PLK1 inhibitor BI-6727, leading to an increase in the radiosensitivity of NSCLC cells. BI-6727 in combination with radiation significantly induced the delayed tumor growth. PLK1-silenced NSCLC cells showed an altered mRNA and protein expression related to DNA damaging, replication, and repairing, including the DNA-dependent protein kinase (DNAPK) and topoisomerase II alpha (TOPO2A). Furthermore, inhibition of PLK1 blocked 2 important DNA repair pathways. To summarize, our study showed PLK1 kinase as an option in the therapy of NSCLC.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Proteínas de Ciclo Celular/antagonistas & inibidores , Quebras de DNA de Cadeia Dupla/efeitos dos fármacos , Reparo do DNA/efeitos dos fármacos , Neoplasias Pulmonares/patologia , Proteínas Serina-Treonina Quinases/antagonistas & inibidores , Proteínas Proto-Oncogênicas/antagonistas & inibidores , Apoptose/efeitos dos fármacos , Carcinoma Pulmonar de Células não Pequenas/patologia , Proteínas de Ciclo Celular/metabolismo , Linhagem Celular Tumoral , Segregação de Cromossomos/efeitos dos fármacos , Replicação do DNA/efeitos dos fármacos , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Proto-Oncogênicas/metabolismo , Pteridinas/farmacologia , Quinase 1 Polo-LikeRESUMO
The Y-chromosome haplogroup C2c1a1a1-M407 is a predominant paternal lineage in Mongolic-speaking populations, especially in Buryats and Kalmyks. However, the origin and internal phylogeny of C2c1a1a1-M407 have not been investigated in detail. In this study, we analyzed twenty-three Y-chromosome sequences of haplogroup C2c1a1a1-M407 and its most closely related clades. We generated a high-resolution phylogenetic tree of haplogroup C2c1a1a1-M407 and its upstream clade C2c1a1-CTS2657, including 32 subclades and 144 non-private Y-chromosome polymorphisms. We discover that all available C2c1a1a1-M407 samples from Mongolic-speaking populations belong to its newly defined downstream clade C2c1a1a1b-F8465, whereas all samples of C2c1a1-CTS2657(xF8465) come from northern Han Chinese, Korean, and Japanese. Furthermore, we observe that C2c1a1a1b-F8465 and its subclade C2c1a1a1b1-F8536 expanded at approximately 0.86 and 0.44 thousand years ago, respectively. Therefore, we conclude that C2c1a1a1-M407 in Mongolic-speaking populations has originated from northeastern Asia. C2c1a1a1b1-F8536, the newly defined subclade of C2c1a1a1-M407, probably represents the genetic relationships between ancient Oyrats, modern Kalmyks, Mongolians, and Buryats.
Assuntos
Povo Asiático/etnologia , Cromossomos Humanos Y/genética , Análise de Sequência de DNA/métodos , Povo Asiático/genética , China/etnologia , Genética Populacional , Haplótipos , Humanos , Japão/etnologia , Filogenia , República da Coreia/etnologiaRESUMO
Gram-negative bacteria produce outer membrane vesicles (OMVs) as delivery vehicles for nefarious bacterial cargo such as virulence factors, which are antibiotic resistance determinants. This study aimed to investigate the impact of polymyxin B treatment on the OMV lipidome from paired polymyxin-susceptible and -resistant Klebsiella pneumoniae isolates. K. pneumoniae ATCC 700721 was employed as a reference strain in addition to two clinical strains, K. pneumoniae FADDI-KP069 and K. pneumoniae BM3. Polymyxin B treatment of the polymyxin-susceptible strains resulted in a marked reduction in the glycerophospholipid, fatty acid, lysoglycerophosphate and sphingolipid content of their OMVs. Conversely, the polymyxin-resistant strains expressed OMVs richer in all of these lipid species, both intrinsically and increasingly under polymyxin treatment. The average diameter of the OMVs derived from the K. pneumoniae ATCC 700721 polymyxin-susceptible isolate, measured by dynamic light scattering measurements, was ~90.6 nm, whereas the average diameter of the OMVs isolated from the paired polymyxin-resistant isolate was ~141 nm. Polymyxin B treatment (2 mg/L) of the K. pneumoniae ATCC 700721 cells resulted in the production of OMVs with a larger average particle size in both the susceptible (average diameter ~124 nm) and resistant (average diameter ~154 nm) strains. In light of the above, we hypothesize that outer membrane remodelling associated with polymyxin resistance in K. pneumoniae may involve fortifying the membrane structure with increased glycerophospholipids, fatty acids, lysoglycerophosphates and sphingolipids. Putatively, these changes serve to make the outer membrane and OMVs more impervious to polymyxin attack.
Assuntos
Membrana Celular/metabolismo , Farmacorresistência Bacteriana , Klebsiella pneumoniae/metabolismo , Lipídeos de Membrana/metabolismo , Polimixina B , Humanos , Klebsiella pneumoniae/isolamento & purificaçãoRESUMO
The House of Aisin Gioro, the imperial clan of Qing dynasty (1644-1911), affected the history of China and the formation of Manchu ethnicity greatly. However, owing to the lack of historical records and archeological evidences, the origin of the House of Aisin Gioro remains ambiguous. To clarify the origin of Aisin Gioro clan, we conducted whole Y-chromosome sequencing on three samples and Y-single-nucleotide polymorphism (Y-SNP) genotyping on other four samples beside those reported in previous work. We confirmed that the paternal lineage of the Aisin Gioro clan belongs to haplogroup C3b1a3a2-F8951, a brother branch of C3*-Star Cluster (currently named as C3b1a3a1-F3796, once linked to Genghis Khan), which is quite different from the predominant lineage C3c-M48 in other Tungusic-speaking populations. We also determined a series of unique Y-SNP markers for the Aisin Gioro clan. Diversity analyses of haplogroup C3b1a3a2-F8951 revealed the early migration of the ancestors of the Aisin Gioro clan from the middle reaches of Amur River to their later settlement in southeastern Manchuria. Hence, our results suggest that the Aisin Gioro clan may be descendants of ancient populations in Transbaikal region and closely related to origin of current Daur populations. Our research indicated that detailed research of stemma and deep sequencing of Y chromosomes are helpful to explore the prehistoric activities of populations lacking historical records and archeological evidences.
Assuntos
Etnicidade/genética , Genealogia e Heráldica , Genética Populacional , Herança Paterna , Filogenia , China , Cromossomos Humanos Y/química , Haplótipos , Sequenciamento de Nucleotídeos em Larga Escala , História do Século XVII , História do Século XVIII , História do Século XIX , História do Século XX , Migração Humana , Humanos , Repetições de Microssatélites , Polimorfismo de Nucleotídeo ÚnicoRESUMO
In previous studies, a specific paternal lineage with a null value for the Y-chromosome short tandem repeat (Y-STR) marker DYS448 was identified as common among Mongolic- and Turkic-speaking populations. This paternal lineage (temporarily named C3*-DYS448del) was determined to be M217+, M93-, P39-, M48-, M407-, and P53.1-, and its origin and phylogeny remain ambiguous. Here, we analyzed Y-chromosome sequences of 10 male that are related this paternal lineage and redefined it as C3b1a1a1a-F1756 (C3b-F1756). We generated a highly revised phylogenetic tree of haplogroup C3b-F1756, including 21 sub-clades and 360 non-private Y-chromosome polymorphisms. Additionally, we performed a comprehensive analysis of the C3*-DYS448del lineage in eastern Eurasia, including 18 270 samples from 297 populations. Whole Y-chromosome sequences, Y-STR haplotypes, and frequency data were used to generate a distribution map, a network, and age estimations for lineage C3*-DYS448del and its sub-lineages. Considering the historical records of the studied populations, we propose that two major sub-branches of C3b-F1756 may correspond to early expansions of ancestors of modern Mongolic- and Turkic-speaking populations. The large number of newly defined Y-chromosome polymorphisms and the revised phylogenetic tree for C3b-F1756 will assist in investigation of the early history of Altaic-speaking populations in the future.
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Cromossomos Humanos Y , Etnicidade/genética , Haplótipos , Repetições de Microssatélites , Herança Paterna , Filogenia , Locos de Características Quantitativas , Evolução Molecular , Marcadores Genéticos , Humanos , Masculino , Mongólia , Polimorfismo de Nucleotídeo Único , TurquiaRESUMO
Since the first publication in 2005, the genome-wide association study (GWAS) strategy has contributed significantly to the understanding of the mechanisms of human genetic diseases. Integrations of statistical methods and systematic biology are important means to explore the GWAS data. Pathway analysis establishes the importance of genetic variants from GWAS and provides insights into their biological significance. It is conducive in correlating the genetic variants, which have only small but interactive changes, to their importance in the biological pathways. At present, pathway analysis has been widely applied to studies of GWAS data, with relatively good results. In the meantime, various analytical methods are being developed and adapted for research on more types of complex data. In this review, we summarize the statistical methods of pathway analysis on GWAS data, and divide them into non-kernel methods and kernel methods. The non-kernel methods include gene set enrichment analysis (GSEA) and hierarchical Bayes prioritization (HBP) analysis, while kernel methods include linear kernel (LIN), identity-by-status kernel (IBS) and powered exponential kernel. We have summarized the calculation principles and features of these statistical methods to provide insights for further developments of new algorithms in GWAS research.
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Doenças Genéticas Inatas/genética , Transdução de Sinais/genética , Algoritmos , Teorema de Bayes , Estudo de Associação Genômica Ampla/métodos , Humanos , Modelos Genéticos , SoftwareRESUMO
A novel concept of using mixed lipids to construct selective peptide-sequence-sensing lyotropic liquid-crystalline (LLC) dispersion systems was investigated. The LLC systems were constructed using a mixture of phytantriol, a lipid that forms lyotropic liquid-crystalline phases, and a novel synthesized peptide-lipid (peplipid) for sensing a target peptide with the RARAR sequence. The internal structure of the dispersed LLC particles was converted from the lamellar structure (liposomes) to the inverse bicontinuous cubic phase (cubosomes) in the presence of the target peptide. The addition of common human proteins did not induce any structural change, indicating a high selectivity of interaction with the target peptide. The concept has potential for the design of targeted controlled release drug delivery agents.
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This review describes the microfluidic techniques developed for the analysis of a single cell. The characteristics of microfluidic (e.g., little sample amount required, high-throughput performance) make this tool suitable to answer and to solve biological questions of interest about a single cell. This review aims to introduce microfluidic related techniques for the isolation, trapping and manipulation of a single cell. The major approaches for detection in single-cell analysis are introduced; the applications of single-cell analysis are then summarized. The review concludes with discussions of the future directions and opportunities of microfluidic systems applied in analysis of a single cell.