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1.
Mol Biol Evol ; 39(5)2022 05 03.
Artículo en Inglés | MEDLINE | ID: mdl-35574660

RESUMEN

Segmental duplications (SDs) constitute a considerable fraction of primate genomes. They contribute to genetic variation and provide raw material for evolution. Groups of SDs are characterized by the presence of shared core duplicons. One of these core duplicons, low copy repeat (lcr)16a, has been shown to be particularly active in the propagation of interspersed SDs in primates. The underlying mechanisms are, however, only partially understood. Alu short interspersed elements (SINEs) are frequently found at breakpoints and have been implicated in the expansion of SDs. Detailed analysis of lcr16a-containing SDs shows that the hominid-specific SVA (SINE-R-VNTR-Alu) retrotransposon is an integral component of the core duplicon in Asian and African great apes. In orang-utan, it provides breakpoints and contributes to both interchromosomal and intrachromosomal lcr16a mobility by inter-element recombination. Furthermore, the data suggest that in hominines (human, chimpanzee, gorilla) SVA recombination-mediated integration of a circular intermediate is the founding event of a lineage-specific lcr16a expansion. One of the hominine lcr16a copies displays large flanking direct repeats, a structural feature shared by other SDs in the human genome. Taken together, the results obtained extend the range of SVAs' contribution to genome evolution from RNA-mediated transduction to DNA-based recombination. In addition, they provide further support for a role of circular intermediates in SD mobilization.


Asunto(s)
Hominidae , Duplicaciones Segmentarias en el Genoma , Animales , Evolución Molecular , Genoma Humano , Hominidae/genética , Humanos , Primates/genética , Retroelementos
2.
Environ Sci Technol ; 57(1): 842-851, 2023 01 10.
Artículo en Inglés | MEDLINE | ID: mdl-36563039

RESUMEN

Following an exceedance of the lead action level for drinking water in 2016, the Pittsburgh Water and Sewer Authority (PWSA) undertook two sampling programs: the required biannual Lead and Copper Rule (LCR) compliance testing and a home sampling program based on customer requests. The LCR sampling results, at locations expected to be elevated when corrosion is not well controlled, had higher concentrations than customer-requested homes, with 90th percentile values for the LCR sites exceeding the action level through 2019 (except for June 2018). Customer-requested concentrations showed greater variability, with the median lead concentration for customer-requested samples below detection for each year of sampling, suggesting only some homes show elevated lead when corrosion control is not fully effective. Corrosion control adjustments brought the utility back into compliance in 2020 (LCR 90th percentile of 5.1 ppb in June 2020); customer-requested sampling after the addition of orthophosphate indicated below detection levels for 59% of samples. Monte Carlo simulations indicate LCR samples do not all represent high lead risk sites, and the application of corrosion control more significantly affects higher lead concentration sites. Broader water quality sampling provides information about specific homes but is not well suited to assessing the efficacy of corrosion control efforts by utilities.


Asunto(s)
Agua Potable , Contaminantes Químicos del Agua , Plomo/análisis , Abastecimiento de Agua , Contaminantes Químicos del Agua/análisis , Calidad del Agua , Corrosión , Cobre/análisis
3.
Surg Today ; 53(8): 940-948, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-36595075

RESUMEN

PURPOSE: The goal of this study was to determine which markers are the most useful as first- and second-line pre-treatment markers in patients with unresectable or recurrent gastric cancer (URGC). METHODS: This study included 101 URGC patients who were treated with first- and second-line chemotherapy. Several prognostic scores based on nutrition and inflammation were analyzed using a receiver operating characteristic (ROC) analysis to determine the most useful prognostic marker. RESULTS: The lymphocyte-to-C-reactive protein ratio (LCR) had the highest area under the curve for both first- and second-line chemotherapy, according to an ROC analysis. An ROC analysis was used to determine the optimal LCR cut-off for the median survival time before first- and second-line chemotherapy, and patients were divided into high- and low-LCR groups. Patients with a high LCR had a significantly longer survival than those with a low LCR before first- and second-line chemotherapy (p = 0.004, p < 0.001, respectively). A low LCR before both first- and second-line chemotherapy was an independent poor prognostic factor in a multivariate analysis. CONCLUSIONS: URGC patients with a low LCR before both first- and second-line chemotherapy had a significantly worse prognosis than those with a high LCR in this study. Nutritional intervention during chemotherapy induction may lead to a better prognosis.


Asunto(s)
Neoplasias Gástricas , Humanos , Pronóstico , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/metabolismo , Proteína C-Reactiva/metabolismo , Estudios Retrospectivos , Recurrencia Local de Neoplasia , Linfocitos/metabolismo
4.
Int J Mol Sci ; 24(6)2023 Mar 22.
Artículo en Inglés | MEDLINE | ID: mdl-36983064

RESUMEN

Health care systems worldwide have been battling the ongoing COVID-19 pandemic. Since the beginning of the COVID-19 pandemic, Lymphocytes and CRP have been reported as markers of interest. We chose to investigate the prognostic value of the LCR ratio as a marker of severity and mortality in COVID-19 infection. Between 1 March and 30 April 2020, we conducted a multicenter, retrospective cohort study of patients with moderate and severe coronavirus disease 19 (COVID-19), all of whom were hospitalized after being admitted to the Emergency Department (ED). We conducted our study in six major hospitals of northeast France, one of the outbreak's epicenters in Europe. A total of 1035 patients with COVID-19 were included in our study. Around three-quarters of them (76.2%) presented a moderate form of the disease, while the remaining quarter (23.8%) presented a severe form requiring admission to the ICU. At ED admission, the median LCR was significantly lower in the group presenting severe disease compared to that with moderate disease (versus 6.24 (3.24-12) versus 12.63 ((6.05-31.67)), p < 0.001). However, LCR was neither associated with disease severity (OR: 0.99, CI 95% (0.99-1)), p = 0.476) nor mortality (OR: 0.99, CI 95% (0.99-1)). In the ED, LCR, although modest, with a threshold of 12.63, was a predictive marker for severe forms of COVID-19.


Asunto(s)
COVID-19 , Humanos , Proteína C-Reactiva/metabolismo , SARS-CoV-2/metabolismo , Pandemias , Estudios Retrospectivos , Linfocitos/metabolismo , Servicio de Urgencia en Hospital
5.
Wiad Lek ; 76(10): 2269-2276, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37948725

RESUMEN

OBJECTIVE: The aim: This study aims to assess the role of platelets and platelet indices as a cost-effective predictive marker of the cervical cancer patient's response before, 15th, and 25th external radiation. PATIENTS AND METHODS: Materials and methods: A total of 54 cervical cancer patients at Dr. Kariadi Hospital were divided into good and poor therapeutic response groups. Measurements of platelet count and indices including PDW, P-LCR, and PCT were carried out before, 15th, and 25th external radiation. RESULTS: Results: There was no difference in platelet counts, MPV, PDW, P-LCR, and PCT in both groups, but patients with decreased MPV and P-LCR values on 15th-25th external radiation had a better therapeutic response (p= 0.005 and 0.007). CONCLUSION: Conclusions: MPV and P-LCR values at 15th to 25th external radiation appeared to decrease further in the group that responded better to therapy.


Asunto(s)
Volúmen Plaquetario Medio , Neoplasias del Cuello Uterino , Femenino , Humanos , Recuento de Plaquetas , Neoplasias del Cuello Uterino/radioterapia , Plaquetas , Hospitales
6.
BMC Cancer ; 22(1): 641, 2022 Jun 11.
Artículo en Inglés | MEDLINE | ID: mdl-35690739

RESUMEN

BACKGROUND: The systemic inflammatory response resulting from the complex interactions between cancer and the host plays an important role in cancer development. Recently, the lymphocyte-C-reactive protein ratio (LCR), which is a hematological and biochemical marker that reflects the systemic inflammatory response and nutritional status, has been reported to be associated with poor survival. Similar results were observed in patients with certain cancer types. However, these studies focused on the preoperative LCR, and thus far, no studies have reported the relationship between postoperative LCR and prognosis in patients with gastric cancer (GC). METHODS: This study enrolled 455 patients with a histopathological diagnosis of gastric adenocarcinoma who underwent curative surgery at our institution between 2005 and 2018. The relationship between both the preoperative and postoperative LCR and the prognosis of patients with GC was retrospectively investigated. RESULTS: Preoperative LCR showed significant correlations with tumor-related factors, such as tumor size, depth of invasion, and lymph node metastasis. By contrast, no correlation was observed between postoperative LCR and tumor-related factors. The 5 year survival rate was significantly worse in patients with low preoperative LCR than in those with high preoperative LCR (65.4% vs. 83.9%, p < 0.0001). Similarly, the 5 year survival rate was also significantly worse in patients with low postoperative LCR than in those with high postoperative LCR (67.0% vs. 84.1%, p < 0.0001). Furthermore, combination analysis of the pre- and postoperative LCR revealed that the prognosis of patients with both low pre- and postoperative LCR was worse in patients with GC (5 year survival rate was 52.0%). A multivariate analysis indicated that a low pre- and postoperative LCR and age and lymph node metastasis were independent prognostic indicators. CONCLUSIONS: The combination of preoperative and postoperative LCR appears to be useful in predicting the prognosis of patients with GC.


Asunto(s)
Neoplasias Gástricas , Proteína C-Reactiva/análisis , Humanos , Metástasis Linfática , Linfocitos/patología , Pronóstico , Estudios Retrospectivos , Neoplasias Gástricas/patología , Síndrome de Respuesta Inflamatoria Sistémica
7.
FASEB J ; 35(6): e21669, 2021 06.
Artículo en Inglés | MEDLINE | ID: mdl-34033138

RESUMEN

The human ß-globin locus control region (LCR) hypersensitive site 2 (HS2) is one of enhancers for transcription of the ß-like globin genes in erythroid cells. Our previous study showed that the LCR HS2 has active chromatin structure before transcriptional induction of the ß-globin gene, while another enhancer LCR HS3 is activated by the induction. To compare functional difference between them, we deleted each HS (ΔHS2 and ΔHS3) from the human ß-globin locus in hybrid MEL/ch11 cells. Deletion of either HS2 or HS3 dramatically diminished the ß-globin transcription and disrupted locus-wide histone H3K27ac and chromatin interaction between LCR HSs and gene. Surprisingly, ΔHS2 weakened interactions between CTCF sites forming the ß-globin topologically associating domain (TAD), while ΔHS3 did not. CTCF occupancy and chromatin accessibility were reduced at the CTCF sites in the ΔHS2 locus. To further characterize the HS2, we deleted the maf-recognition elements for erythroid activator NF-E2 at HS2. This deletion decreased the ß-globin transcription and enhancer-promoter interaction, but did not affect interactions between CTCF sites for the TAD. In light of these results, we propose that the HS2 has a role in forming a ß-globin TAD by activating neighboring CTCF sites and this role is beyond typical enhancer activity.


Asunto(s)
Factor de Unión a CCCTC/metabolismo , Cromatina/química , Elementos de Facilitación Genéticos , Transcripción Genética , Activación Transcripcional , Globinas beta/genética , Sitios de Unión , Factor de Unión a CCCTC/genética , Cromatina/genética , Cromatina/metabolismo , Humanos , Regiones Promotoras Genéticas , Globinas beta/metabolismo
8.
Environ Res ; 207: 112140, 2022 05 01.
Artículo en Inglés | MEDLINE | ID: mdl-34592255

RESUMEN

There is no safe level of lead exposure. As exposure from point sources like lead paint have decreased, non-point sources such as drinking water have become a greater proportional source of total lead exposure. Even at low levels, lead exposure is shown to harm children, contributing to impaired development as well as learning and behavioral issues. This paper summarizes the key results of an Environmental Defense Fund (EDF) pilot study conducted at 11 child care facilities in 4 US states to evaluate approaches to testing and remediating lead in water at child care facilities. Over 75% of first draw samples contained lead levels under the 1 µg/L level recommended by the American Academy of Pediatrics (AAP). However, 10 of 11 child care facilities produced at least one sample above 1 µg/L. Fixture flushing, aerator cleaning, and fixture replacement were evaluated as remediation strategies. Fixture replacement was effective when initial lead was above 5 µg/L. Aerator cleaning did not have a measurable effect on lead levels for most fixtures but unexpectedly significantly increased lead levels in approximately 30% of fixtures. The 2021 Lead and Copper Rule (LCR) revision was applied to study data to determine whether updates would flag cases of low-level lead in child care settings and was found insufficient to prompt mitigation unless high lead was present at most taps.


Asunto(s)
Agua Potable , Niño , Cuidado del Niño , Cobre , Agua Potable/análisis , Exposición a Riesgos Ambientales , Humanos , Plomo/análisis , Proyectos Piloto , Estados Unidos
9.
Platelets ; 33(2): 291-297, 2022 Feb 17.
Artículo en Inglés | MEDLINE | ID: mdl-33784226

RESUMEN

Our objective was to analyze if there was a significant relationship between platelet parameters (PLT, MPV, PDW, P-LCR, PCT) among dengue, its serological subgroups and controls. Serologically proven adult patients with dengue {(n = 238) (NS1 positive = 218, IgM positive = 14, NS1 & IgM positive = 6)} and age- and gender-matched controls (n = 254) were included. The MPV, PDW and P-LCR were significantly higher, and PLT and PCT were significantly lower in cases compared with controls. Cases as well as controls showed a positive correlation between PLT and PCT, both parameters individually showed negative correlation with MPV, PDW, P-LCR. MPV, PDW and P-LCR showed positive correlation with each other. The results were similar in the serological subgroups. Comparison of our results with other studies points toward an overall hyperdestructive etiology for thrombocytopenia in dengue. There were two subgroups of cases based on the severity of thrombocytopenia. The mean/median value of all the platelet parameters was lesser in the ≤20k group than the >20k group, except for PDW, which was high although not statistically significant. Suppression of megakaryopoiesis with concomitant immune destruction of platelets in severe dengue could explain low MPV and P-LCR with a high PDW in view of the presence of microthrombocytes as a result of immune destruction. Although an overall hyperdestructive mechanism contributes to thrombocytopenia in dengue, regular monitoring of the platelet indices could reflect the status of megakaryopoiesis and thrombokinetic axis, thus aiding easy determination of pathophysiology and treatment.


Asunto(s)
Plaquetas/metabolismo , Dengue/sangre , Estudios de Casos y Controles , Estudios Transversales , Dengue/patología , Hospitalización , Humanos , Estudios Retrospectivos
10.
J Nondestr Eval ; 41(3): 63, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36097513

RESUMEN

Non-destructive stress measurement by ultrasonic testing is based on calculating the acoustoelastic modulus obtained from the relationship between material stress and sound wave velocity. A critically refracted longitudinal (LCR) wave, which is a bulk longitudinal wave penetrating below and parallel to the surface below an effective depth, is most suitable for ultrasonic stress measurement tests because it exhibits a relatively large change in travel time in response to a change in stress. In particular, the residual stress distribution through the thickness of the subject can be calculated if transducers of different frequencies are applied because of the characteristic of propagation to different depths of penetration depending on the frequency. The main purpose of this study was to visualize the internal or residual stress distribution through the thickness of rails using LCR waves. To this end, LCR probes with different center frequencies were designed and manufactured, and the residual stress values ​​of an unused railroad rail and two used railroad rails operated under different conditions were calculated. This was done using the ultrasonic signals received from each probe, of which the distributions were mapped. Through these mapping results, different residual stress values could be calculated according to the depth. The differences in residual stress generation and distribution according to the conditions surrounding the contact between train wheels and rails, and their characteristics, were visualized and analyzed. As a result, it could be concluded that the non-destructive evaluation technique using LCR waves could detect differences in the residual stress of a rail, and thus can be used to measure the residual stress of the rail accurately.

11.
Habitat Int ; 123: None, 2022 May.
Artículo en Inglés | MEDLINE | ID: mdl-35685950

RESUMEN

The application of last-generation spatial data modelling, integrating Earth Observation, population, economic and other spatially explicit data, enables insights into the sustainability of the global urbanisation processes with unprecedented detail, consistency, and international comparability. In this study, the land use efficiency indicator, as developed in the Sustainable Development Goals, is assessed globally for the first time at the level of Functional Urban Areas (FUAs). Each FUA includes the city and its commuting zone as inferred from statistical modelling of available spatial data. FUAs represent the economic area of influence of each urban centre. Hence, the analysis of land consumption within their boundary has significance in the fields of spatial planning and policy analyses as well as many other research areas. We utilize the boundaries of more than 9,000 FUAs to estimate the land use efficiency between 1990 and 2015, by using population and built-up area data extracted from the Global Human Settlement Layer. This analysis shows how, in the observed period, FUAs in low-income countries of the Global South evolved with rates of population growth surpassing the ones of land consumption. However, in almost all regions of the globe, more than half of the FUAs improved their land use efficiency in recent years (2000-2015) with respect to the previous decade (1990-2000). Our study concludes that the spatial expansion of urban areas within FUA boundaries is reducing compactness of settlements, and that settlements located within FUAs do not display higher land use efficiency than those outside FUAs.

12.
Expert Rev Mol Med ; 23: e19, 2021 12 01.
Artículo en Inglés | MEDLINE | ID: mdl-34847982

RESUMEN

Human papillomavirus 16 (HPV16) infection is the aetiologic factor for the development of cervical dysplasia and is regarded as highly carcinogen, because it is implicated in more than 50% of cervical cancer cases, worldwide. The tumourigenic potential of HPV16 has triggered the extensive sequence analysis of viral genome in order to identify nucleotide variations and amino acid substitutions that influence viral oncogenicity and subsequently the initiation and progression of cervical cancer. Nowadays, specific mutations of HPV16 DNA have been associated with an increased risk of high-grade squamous intraepithelial lesions and invasive cervical cancer (ICC) development, including E6: Q14H, H78Y, L83V, Ε7: N29S, S63F, E2: H35Q, P219S, T310K, E5: I65V, whereas highly conserved regions of viral DNA have been extensively characterised. In addition, numerous novel HPV16 mutations are observed among the studied populations from various geographic regions, hence advocating that different HPV16 strains seem to emerge with different tumourigenic capacities. The present review focuses on the variability of the early genes and the long control region, emphasising on the association of specific mutations with the development of severe dysplasia. Finally, it evaluates whether specific regions of HPV16 DNA are able to serve as valuable biomarkers for cervical cancer risk.


Asunto(s)
Proteínas Oncogénicas Virales , Infecciones por Papillomavirus , Neoplasias del Cuello Uterino , Femenino , Papillomavirus Humano 16/genética , Humanos , Proteínas Oncogénicas Virales/genética , Infecciones por Papillomavirus/genética , Proteínas Represoras , Neoplasias del Cuello Uterino/genética
13.
J Med Virol ; 93(9): 5555-5559, 2021 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-34019701

RESUMEN

We aimed to find the most useful biomarker by examining the prognostic effect of neutrophil-lymphocyte ratio (NLR), lymphocyte-monocyte ratio (LMR), platelet-lymphocyte ratio (PLR), and lymphocyte-C reactive protein ratio (LCR) in patients with coronavirus disease 2019 (COVID-19). Three hundred and four patients diagnosed with COVID-19 infection in our hospital within 5 months (April-August 2020) were examined. Laboratory values and demographic findings of the patients were analyzed retrospectively. Thirty-six patients were diagnosed with severe cases. The ratio of NLR, LMR, PLR, and LCR of patients with severe and those with nonsevere clinical symptoms were statistically analyzed. The NLR and PLR ratios of those with severe clinical symptoms were significantly higher (p < 0.001), the LCR rate was significantly lower (p < 0.001), and there was no significant difference in the LMR rate (p = 0.199). When we examined other peripheral blood parameters, we found that CRP was high, lymphocyte and monocyte were low (p < 0.001), but neutrophil (p = 0.416) and platelet (p = 0.998) were not statistically different between the groups. According to the results, routine blood values are abnormal in patients with COVID-19. NLR, PLR, and LCR ratios can be used as more significant biomarkers than other values in predicting the prognosis of patients.


Asunto(s)
Plaquetas , COVID-19/sangre , Linfocitos , Monocitos , Neutrófilos , SARS-CoV-2 , Adulto , Anciano , Biomarcadores/sangre , Proteína C-Reactiva/análisis , Femenino , Humanos , Masculino , Persona de Mediana Edad , Monocitos/metabolismo , Pronóstico , Estudios Retrospectivos
14.
Virol J ; 18(1): 94, 2021 05 03.
Artículo en Inglés | MEDLINE | ID: mdl-33941222

RESUMEN

BACKGROUND: Variations in human papillomavirus (HPV) E6 and E7 have been shown to be closely related to the persistence of the virus and the occurrence and development of cervical cancer. Long control region (LCR) of HPV has been shown multiple functions on regulating viral transcription. In recent years, there have been reports on E6/E7/LCR of HPV-16 and HPV-58, but there are few studies on HPV-52, especially for LCR. In this study, we focused on gene polymorphism of the HPV-52 E6/E7/LCR sequences, assessed the effects of variations on the immune recognition of viral E6 and E7 antigens, predicted the effect of LCR variations on transcription factor binding sites and provided more basic date for further study of E6/E7/LCR in Chengdu, China. METHODS: LCR/E6/E7 of the HPV-52 were amplified and sequenced to do polymorphic and phylogenetic analysis. Sequences were aligned with the reference sequence by MEGA 7.0 to identify SNP. A neighbor-joining phylogenetic tree was constructed by MEGA 7.0, followed by the secondary structure prediction of the related proteins using PSIPRED 4.0. The selection pressure of E6 and E7 coding regions were estimated by Bayes empirical Bayes analysis of PAML 4.9. The HLA class-I and II binding peptides were predicted by the Immune Epitope Database server. The B cell epitopes were predicted by ABCpred server. Transcription factor binding sites in LCR were predicted by JASPAR database. RESULTS: 50 SNP sites (6 in E6, 10 in E7, 34 in LCR) were found. From the most variable to the least variable, the nucleotide variations were LCR > E7 > E6. Two deletions were found between the nucleotide sites 7387-7391 (TTATG) and 7698-7700 (CTT) in all samples. A deletion was found between the nucleotide sites 7287-7288 (TG) in 97.56% (40/41) of the samples. The combinations of all the SNP sites and deletions resulted in 12 unique sequences. As shown in the neighbor-joining phylogenetic tree, except for one belonging to sub-lineage C2, others sequences clustered into sub-lineage B2. No positive selection was observed in E6 and E7. 8 non-synonymous amino acid substitutions (including E3Q and K93R in the E6, and T37I, S52D, Y59D, H61Y, D64N and L99R in the E7) were potential affecting multiple putative epitopes for both CD4+ and CD8+ T-cells and B-cells. A7168G was the most variable site (100%) and the binding sites for transcription factor VAX1 in LCR. In addition, the prediction results showed that LCR had the high probability binding sites for transcription factors SOX9, FOS, RAX, HOXA5, VAX1 and SRY. CONCLUSION: This study provides basic data for understanding the relation among E6/E7/LCR mutations, lineages and carcinogenesis. Furthermore, it provides an insight into the intrinsic geographical relatedness and biological differences of the HPV-52 variants, and contributes to further research on the HPV-52 therapeutic vaccine development.


Asunto(s)
Alphapapillomavirus , Proteínas Oncogénicas Virales , Proteínas E7 de Papillomavirus , Infecciones por Papillomavirus , Filogenia , Alphapapillomavirus/genética , Teorema de Bayes , China , Epítopos de Linfocito B , Femenino , Humanos , Proteínas Oncogénicas Virales/genética , Proteínas E7 de Papillomavirus/genética , Infecciones por Papillomavirus/virología , Factores de Transcripción , Neoplasias del Cuello Uterino/virología , Desarrollo de Vacunas
15.
Genomics ; 112(6): 5066-5071, 2020 11.
Artículo en Inglés | MEDLINE | ID: mdl-32898643

RESUMEN

Persistent infections by high-risk human papillomavirus (HR-HPV) are a necessary condition, but not sufficient for cervical cancer development. Genetic variants of HR-HPV appear to be related to the risk of persistent infections. The study performed a functional evaluation of variants of the HPV-31 promoter region (LCR). For this, cloning and subcloning of variants HPV-31/UFPE-21 HPV-31/UFPE-89, HPV-31/UFPE-66, E2 gene and prototype HPV-31 were performed. Transfection with different concentrations of E2 was done and the concentration of 25 ng was determined to be ideal for LCR activation. HPV-31/UFPE-21 and HPV-31/UFPE-89 have a greater ability to alter Nluc reporter gene expression levels and HPV-31/UFPE-66 showed decreased levels of gene expression of Nluc reporter gene compared to control. Statistical analysis showed a significant difference between the polymorphic LCR regions and the control (p < 0.0001). A more refined profile of variants of HPV-31 and its importance for the prognosis of cervical lesions begins to be drawn.


Asunto(s)
Papillomavirus Humano 31/genética , Regiones Promotoras Genéticas , Proteínas de Unión al ADN/metabolismo , Células HeLa , Humanos , Polimorfismo Genético , Transactivadores/metabolismo , Activación Transcripcional , Proteínas Virales/metabolismo
16.
Physiol Genomics ; 52(1): 1-14, 2020 01 01.
Artículo en Inglés | MEDLINE | ID: mdl-31762410

RESUMEN

Here we postulate that the heritability of complex disease traits previously ascribed solely to the inheritance of the nuclear and mitochondrial genomes is broadened to encompass a third component of the holobiome, the microbiome. To test this, we expanded on the selectively bred low capacity runner/high capacity runner (LCR/HCR) rat exercise model system into four distinct rat holobiont model frameworks including matched and mismatched host nuclear and mitochondrial genomes. Vertical selection of varying nuclear and mitochondrial genomes resulted in differential acquisition of the microbiome within each of these holobiont models. Polygenic disease risk of these novel models were assessed and subsequently correlated with patterns of acquisition and contributions of their microbiomes in controlled laboratory settings. Nuclear-mitochondrial-microbiotal interactions were not for exercise as a reporter of health, but significantly noted for increased adiposity, increased blood pressure, compromised cardiac function, and loss of long-term memory as reporters of disease susceptibility. These findings provide evidence for coselection of the microbiome with nuclear and mitochondrial genomes as an important feature impacting the heritability of complex diseases.


Asunto(s)
Núcleo Celular/genética , Microbioma Gastrointestinal/genética , Predisposición Genética a la Enfermedad , Genoma Mitocondrial , Adiposidad/genética , Animales , Conducta Animal , Presión Sanguínea/genética , Peso Corporal/genética , Enfermedades Cardiovasculares/genética , Cognición , ADN Mitocondrial/genética , Condicionamiento Físico Animal , Ratas , Factores de Riesgo , Selección Genética , Remodelación Ventricular/genética
17.
J Med Virol ; 92(3): 372-381, 2020 03.
Artículo en Inglés | MEDLINE | ID: mdl-31670402

RESUMEN

Human papillomavirus (HPV)16 gene mutation is usually associated with persistent HPV infection and cervical intraepithelial neoplasia (CIN). However, the functional implications of HPV16 mutations remain poorly understood.145 LCR/E6/E7 of the HPV16 isolates were amplified and sequenced, and HPV16 integration status was detected. In total, 89 SNPs (68 in the LCR, 13 in E6, 8 in E7) were discovered, 11 of which were nonsynonymous mutations (8 in E6, 3 in E7). The H85Y and E120D variants in E6 were significantly reduced in the high-grade squamous intraepithelial lesion (HSIL) group compared to the T," a potential binding site for TATA-binding protein, is the most common in LCR variants. A4 (Asian) was associated with an increased risk of HSIL compared to A1-3(P = .009). The H85/E120 in E6 and N29 in HPV16 E7 might play a critical role in carcinogenesis by disrupting p53 and Rb degradation due to affecting their interaction, respectively. In a word, the findings in this study provide preventative and therapeutic interventions of HPV16 -related cervical lesions/cancer.


Asunto(s)
Papillomavirus Humano 16/genética , Papillomavirus Humano 16/patogenicidad , Proteínas Oncogénicas Virales/genética , Proteínas E7 de Papillomavirus/genética , Infecciones por Papillomavirus/virología , Proteínas Represoras/genética , Displasia del Cuello del Útero/virología , Neoplasias del Cuello Uterino/virología , Adulto , Anciano , Sustitución de Aminoácidos , China , ADN Viral , Femenino , Técnicas de Genotipaje , Humanos , Persona de Mediana Edad , Mutación , Filogenia , Conformación Proteica , Lesiones Intraepiteliales Escamosas/virología , Integración Viral/genética , Adulto Joven
18.
Int J Med Sci ; 17(7): 931-938, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32308546

RESUMEN

Objective: High-risk human papillomavirus (HPV) E6 and E7 proteins are the major oncoproteins involved in the tumorigenesis of cervical cancer. The long control region (LCR) in HPV plays an important role in regulating the expression of the E6 and E7 oncogenes. In the current study, we investigated the association of HPV16 LCR variations with cervical cancer. Methods: A total of 139 HPV16-positive cervical cancer patients (case group) and 116 HPV16-positive asymptomatic individuals (control group) were enrolled in the current study. Then, the HPV16 LCR was sequenced to determine the association between LCR variations and cervical cancer. Results: In the current study, HPV16 A1-A3 (19.4%), A4 (78.4%) and D3 (2.2%) variants were found in the case group. However, only A1-A3 (34.5%) and A4 variants (65.5%) were found in the control group. The distribution of the HPV16 variants between the case and control groups was significantly different (P=0.009). Moreover, a total of eleven variations (A7167G, A7173C, C7176T, C7200T, T7269C, C7286A, C7729A, C7763T, A7841G, G7867A and T24C) were significantly different between the case and control groups (P<0.05). For the sub-lineage analysis, only C7873G variations were significantly different between the case and control groups in the A4 (As) variant (P=0.039). Conclusion: Our results showed that specific variations in the HPV16 LCR were associated with cervical cancer. Our study will provide a good reference for further understanding of the relationship between HPV16 LCR variation and cervical cancer.


Asunto(s)
Pueblo Asiatico/genética , Papillomavirus Humano 16/genética , Infecciones por Papillomavirus/complicaciones , Infecciones por Papillomavirus/virología , Neoplasias del Cuello Uterino/microbiología , Estudios de Casos y Controles , Femenino , Frecuencia de los Genes , Variación Genética , Papillomavirus Humano 16/patogenicidad , Humanos , Filogenia
19.
Sensors (Basel) ; 20(19)2020 Oct 08.
Artículo en Inglés | MEDLINE | ID: mdl-33050092

RESUMEN

The accurate measurement of stress at different depths in the end face of a high-pressure compressor rotor is particularly important, as it is directly related to the assembly quality and overall performance of aero-engines. The ultrasonic longitudinal critically refracted (LCR) wave is sensitive to stress and can measure stress at different depths, which has a prominent advantage in stress non-destructive measurements. In order to accurately characterize the propagation depth of LCR waves and improve the spatial resolution of stress measurement, a finite element model suitable for the study of LCR wave propagation depths was established based on a wave equation and Snell law, and the generation and propagation process of LCR waves are analyzed. By analyzing the blocking effect of grooves with different depths on the wave, the propagation depth of the LCR wave at seven specific frequencies was determined in turn. On this basis, the LCR wave propagation depth model is established, and the effects of wedge materials, piezoelectric element diameters, and excitation voltages on the propagation depth of LCR waves are discussed. This study is of great significance to improve the spatial resolution of stress measurements at different depths in the end face of the aero-engine rotor.

20.
Hemoglobin ; 44(3): 214-217, 2020 May.
Artículo en Inglés | MEDLINE | ID: mdl-32605393

RESUMEN

A woman completely lacking Hb A2 on the high performance liquid chromatography (HPLC) analysis, presented with a novel deletional (εγ)δß0-thal and a δ-globin gene variant. This combination causes a ß-thalassemia (ß-thal) minor phenotype. The woman was referred by a hematologist due to abnormal blood counts. Multiplex ligation-dependent probe amplification (MLPA) and microarray analysis showed a heterozygous, 177 kb long deletion that removed the locus control region enhancer plus the ε, Gγ and Aγ genes. Additional sequencing revealed a novel variant HBD: c.209G>A, p.Gly70Asp in the heterozygous state, called Hb A2-Gebenstorf. The combination of the two variants explains the lack of Hb A2 in this woman.


Asunto(s)
Hemoglobina A2/genética , Mutación , Talasemia beta/diagnóstico , Talasemia beta/genética , Globinas delta/genética , Alelos , Cromatografía Líquida de Alta Presión , Análisis Mutacional de ADN , Índices de Eritrocitos , Femenino , Estudios de Asociación Genética/métodos , Predisposición Genética a la Enfermedad , Pruebas Genéticas , Heterocigoto , Humanos , Fenotipo , Talasemia beta/sangre
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