RESUMEN
This paper investigates the deformation mechanism and energy absorption behaviour of 316 L triply periodic minimal surface (TPMS) structures with uniform and graded wall thicknesses fabricated by the selective laser melting technique. The uniform P-surface TPMS structure presents a single-level stress plateau for energy absorption and a localized diagonal shear cell failure. A graded strategy was employed to break such localized geometrical deformation to improve the overall energy absorption and to provide a double-level function. Two segments with different wall thicknesses separated by a barrier layer were designed along the compression direction while keeping the same relative density as the uniform structure. The results show that the crushing of the cells of the graded P-surface TPMS structure occurs first within the thin segment and then propagates to the thick segment. The stress-strain response shows apparent double stress plateaus. The stress level and length of each plateau can be adjusted by changing the wall thickness and position of the barrier layer between the two segments. The total energy absorption of the gradient TPMS structure was also found slightly higher than that of the uniform TPMS counterparts. The gradient design of TPMS structures may find applications where the energy absorption requires a double-level feature or a warning function.
RESUMEN
Our previous study in an isolated population showed an association between a genetic variant in the catalase gene (CAT) and essential hypertension (EH). This study indicates that three variants in the promoter and 5'-UTR region of CAT are predominant in Chinese Han, and they form two major haplotypes. A case-control study showed that the CATH2 haplotype confers susceptibility to EH (Pgenotype=0.0017, and Pallilc=0.00078). Subjects bearing CATH1/CATH2 and CATH2/CATH2 genotypes demonstrated a higher susceptibility to EH than CATH1/CATH1 homozygotes, with odds ratios of 1.474 and 1.625, respectively. Also, CATH1/CATH1 individuals had a later-onset age (P=0.015). Expression analysis using luciferase reporter vectors indicated that the CATH1 haplotype showed a lower transcriptional activity than the haplotype CATH2 (P<0.05 in all four cell lines), and we observed similar results in the endogenous allelic expression ratios of CATH1/CATH2 in cell lines. In contrast, most CATH1 haplotypes showed a higher transcription level than CATH2 haplotypes (10 out of 11 or 90.9%) in blood from normal individuals (P<0.01). We therefore hypothesize that CATH1 and CATH2 may play alternating roles at different level of oxidative stress.
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Catalasa/genética , Hipertensión/genética , Mutación , Anciano , Alelos , Secuencia de Bases , China , Femenino , Humanos , Hipertensión/etnología , Masculino , Persona de Mediana Edad , Datos de Secuencia Molecular , Estrés Oxidativo , Estructura Secundaria de Proteína , RiesgoRESUMEN
BACKGROUND: Recent whole genome association studies have independently identified multiple prostate cancer (PC) risk variants on 8q24. We have evaluated association of common variants in this region with PC susceptibility and tumor aggressiveness in a sample of European American men. METHODS: Forty-nine tagging SNPs including three previously reported significant variants (rs1447295, rs6983267, rs16901979) and seven variants in the 5' upstream region of the MYC proto-oncogene were tested for association with susceptibility to PC and tumor aggressiveness in 596 histologically verified PC cases and 567 ethnically matched controls. RESULTS: Significant associations with susceptibility to PC were found at 17 SNPs, four of which (rs1016342, rs1378897, rs871135, and rs6470517) remained significant after adjusting for multiple corrections. One of the associated SNPs, rs871135, is located in the putative gene POU5F1P1 within the 8q24 region. An in slico analysis showed that the associated variant of this SNP alters a transcription factor implicating a plausible regulatory role. Additionally, one of the significantly associated SNPs, rs6470517, with PC susceptibility showed a significant over-representation of the G allele in cases with aggressive tumor. CONCLUSIONS: Although this study does not directly confirm associations of the three specific SNPs (cited above), it corroborates reported signals of association in 8q24 reaffirming that genetic variation on 8q24 influences susceptibility to PC in men of European ancestry. Although our study did not confirm the allelic association of rs1447295, meta-analysis of this SNP provided support to previous reported associations. Further, this study implicates the 8q24 region with aggressive forms of PC.
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Cromosomas Humanos Par 8 , Neoplasias de la Próstata/etnología , Neoplasias de la Próstata/genética , Población Blanca/genética , Población Blanca/estadística & datos numéricos , Adulto , Anciano , Anciano de 80 o más Años , Frecuencia de los Genes , Predisposición Genética a la Enfermedad/etnología , Variación Genética , Estudio de Asociación del Genoma Completo , Humanos , Masculino , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple , Neoplasias de la Próstata/patología , Proto-Oncogenes Mas , Factores de Riesgo , Índice de Severidad de la EnfermedadRESUMEN
BACKGROUND: A genome wide association study found significant association of a sequence variant, rs7566605, in the insulin-induced gene 2 (INSIG2) with obesity. However, the association remained inconclusive in follow-up studies. We tested for association of four tagging SNPs (tagSNPs) including this variant with body mass index (BMI) and abdominal circumference (ABDCIR) in the Samoans of the Western Pacific, a population with high levels of obesity. METHODS: We studied 907 adult Samoan participants from a longitudinal study of adiposity and cardiovascular disease risk in two polities, American Samoa and Samoa. Four tagSNPs were identified from the Chinese HapMap database based on pairwise r2 of >or=0.8 and minor allele frequency of >or=0.05. Genotyping was performed using the TaqMan assay. Tests of association with BMI and ABDCIR were performed under the additive model. RESULTS: We did not find association of rs7566605 with either BMI or ABDCIR in any group of the Samoans. However, the most distally located tagSNPs in Intron 3 of the gene, rs9308762, showed significant association with both BMI (p-value 0.024) and ABDCIR (p-value 0.009) in the combined sample and with BMI (p-value 0.038) in the sample from Samoa. CONCLUSION: Although rs7566605 was not significantly associated with obesity in our study population, we can not rule out the involvement of INSIG2 in obesity related traits as we found significant association of another tagSNP in INSIG2 with both BMI and ABDCIR. This study suggests the importance of comprehensive assessment of sequence variants within a gene in association studies.
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Péptidos y Proteínas de Señalización Intracelular/genética , Proteínas de la Membrana/genética , Obesidad/genética , Adiposidad/genética , Adulto , Índice de Masa Corporal , Femenino , Predisposición Genética a la Enfermedad , Estudio de Asociación del Genoma Completo , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Fenotipo , Polimorfismo de Nucleótido Simple , Samoa , Circunferencia de la Cintura/genéticaRESUMEN
AIM: To perform a comprehensive evaluation of association of common genetic variants in candidate genes in the dopaminergic pathway with schizophrenia in a sample from Croatian population. METHODS: A case-control association study was performed on 104 unrelated patients with schizophrenia recruited from a psychiatric hospital in Zagreb and 131 phenotypically normal Croatian subjects. Forty-nine tagging single nucleotide polymorphisms (tagSNPs) in 8 candidate genes in the dopaminergic pathway were identified from the HapMap database and tested for association. Genotyping was performed using the SNPlex platform. Statistical analysis was conducted to assess allelic and genotypic associations between cases and controls using a goodness of fit chi(2) test and trend test, respectively; adjustment for multiple testing was done by permutation based analysis. RESULTS: Significant allele frequency differences between schizophrenia cases and controls were observed at 4 tagSNPs located in the genes DRD5, HTR1B1, DBH, and TH1 (P<0.005). A trend test also confirmed the genotypic association (P<0.001) of these 4 tagSNPs. Additionally, moderate association (P<0.05) was observed with 8 tagSNPs on SLC6A3, DBH, DRD4, SLC6A4, and COMT. CONCLUSIONS: Common genetic variants in genes involved in the dopaminergic pathway are associated with schizophrenia in the populations of Caucasian descent.
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Dopamina/metabolismo , Variación Genética , Polimorfismo de Nucleótido Simple , Esquizofrenia/genética , Adulto , Anciano , Estudios de Casos y Controles , Croacia , Bases de Datos Genéticas , Dopamina/genética , Femenino , Frecuencia de los Genes , Predisposición Genética a la Enfermedad , Humanos , Masculino , Persona de Mediana Edad , Receptores Dopaminérgicos/genéticaRESUMEN
Metabolic syndrome (MS), a constellation of metabolic risk factors associated with development of cardiovascular diseases and Type 2 diabetes (T2D), has emerged as a public health problem of enormous proportions in developed and developing countries. We have reported previously its prevalence in several island populations of the Eastern Adriatic coast of Croatia. In spite of leading a relatively traditional life style pattern including adherence to a Mediterranean diet, the prevalence of MS in these populations is high and comparable to that in developed nations. However, data on prevalence of MS among the mainland Croatian populations is limited. Therefore, we conducted a study in an outbred population comprising of Croats, Hungarians and Serbs from the Baranja region of mainland Croatia. Although this is an ethnically heterogeneous population, the constituent groups exchange mates and therefore, are not reproductively isolated. The life style patterns are also similar. Overall prevalence of MS, assessed by the National Cholesterol Education Program (NCEP) criteria, is 40% (35% in males and 42% in females) with Body Mass Index (BMI) as the predictor of obesity and 42% (52% in males and 39% in females) with Waist Hip Ratio (WHR) as the predictor of obesity. It is likely that, in addition to genetic risk factors, a host of environmental factors that include dietary habits and relatively urban life style in a modernized society have influenced the levels of the constituent metabolic traits leading to an increased prevalence of MS.
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Síndrome Metabólico/epidemiología , Adolescente , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Índice de Masa Corporal , Enfermedades Cardiovasculares , Croacia/epidemiología , Diabetes Mellitus Tipo 2 , Dislipidemias , Femenino , Intolerancia a la Glucosa , Humanos , Masculino , Síndrome Metabólico/etnología , Persona de Mediana Edad , Obesidad , Prevalencia , Factores de Riesgo , Relación Cintura-Cadera , Adulto JovenRESUMEN
BACKGROUND: Apolipoprotein E (APOE) and elastin (ELN) are plausible candidate genes involved in the pathogenesis of stroke. We tested for association of variants in APOE and ELN with subarachnoid hemorrhage (SAH) in a population-based study. We genotyped 12 single nucleotide polymorphisms (SNPs) on APOE and 10 SNPs on ELN in a sample of 309 Caucasian individuals, of whom 107 are SAH cases and 202 are age-, race-, and gender-matched controls from the Greater Cincinnati/Northern Kentucky region. Associations were tested at genotype, allele, and haplotype levels. A genomic control analysis was performed to check for spurious associations resulting from population substructure. RESULTS: At the APOE locus, no individual SNP was associated with SAH after correction for multiple comparisons. Haplotype analysis revealed significant association of the major haplotype (Hap1) in APOE with SAH (p = 0.001). The association stemmed from both the 5' promoter and the 3' region of the APOE gene. APOE epsilon2 and epsilon 4 were not significantly associated with SAH. No association was observed for ELN at genotype, allele, or haplotype level and our study failed to confirm previous reports of ELN association with aneurysmal SAH. CONCLUSION: This study suggests a role of the APOE gene in the etiology of aneurysmal SAH.
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Apolipoproteínas E/genética , Elastina/genética , Hemorragia Subaracnoidea/genética , Adulto , Estudios de Casos y Controles , Femenino , Frecuencia de los Genes , Predisposición Genética a la Enfermedad , Variación Genética , Humanos , Masculino , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple , Análisis de Secuencia de ADNRESUMEN
The origins of the suburban native of shanghai are varied. With the methods of correlation analysis and principal analysis, we random sampled the surnames of 13 villages and towns located in the districts of Shanghai, and found that Jading, Pudong, Nanhui and the east part of Fengxian make up the group of northeast part, while Jinshan, Songjiang, Qingpu and Chongming make up a completely different one from the other. The surnames of Nanxiang's origin are complex, while Maqiao and Jinhui's are of special kind. The surnames recorded in pedigree have apparent correlation with the modern ones. Moreover, the surnames of northeast part are mainly derived from the areas north to Yangtze River, but those of southwest part come from the areas south to Yangtze River. This explains that the origins of the two districts' throng may be different. The residents of the northeast part, which formed land comparatively recent, probably came from north areas after Tang and Song periods, while those of southeast part came from other northern areas. The residents of shell bar districts such as Maqiao and Jinhui have inherited relation with the culture of remote antiquities of Maqia. The contributing factors of surname are diversified. By researching into the scope of intermarriage of 20th century in Jinhui, we found that before 70's, the intermarriage radius was fixed in 5 kilometers because of match maker custom; in the 70's & 80's, unrestrained love reduced the intermarriage radius into same village about 3 kilometers; after in 90's, the intermarry radius expand to every province because of the rapid social and economic development. The intermarriage scope and consanguinity natural diffuseness can stand for the situations in shanghai and in large parts of south China. The assimilation of adjacent villages under matchmaker custom takes over 2000 years, while takes over 7000 years under unrestrained love. We can see that the impact of the natural diffuseness is rather weak, and the mixed living of emigrants is the main factor. The history of every colony's adjacent living is far shorter than that of assimilation. So there is almost no mixed race in this period. The most parts of south China's situations should be similar. The broken of traditional intermarry suggests us that the auto-disappear speed of abundant genetic resource is high. It is now the most pressure time to gather and research our genetic resource.
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Matrimonio/estadística & datos numéricos , Nombres , Población Suburbana/estadística & datos numéricos , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , China , Recolección de Datos/métodos , Recolección de Datos/estadística & datos numéricos , Femenino , Humanos , Masculino , Matrimonio/tendencias , Persona de Mediana Edad , Estadística como AsuntoRESUMEN
BACKGROUND: The electron transport chain, Rubisco and stomatal conductance are important in photosynthesis. Little is known about their combined responses to heat treatment at different temperatures and following recovery in grapevines (Vitis spp.) which are often grown in climates with high temperatures. METHODOLOGY/FINDINGS: The electron transport function of photosystem II, the activation state of Rubisco and the influence of stomatal behavior were investigated in grapevine leaves during heat treatments and following recovery. High temperature treatments included 35, 40 and 45°C, with 25°C as the control and recovery temperature. Heat treatment at 35°C did not significantly (P>0.05) inhibit net photosynthetic rate (P(n)). However, with treatments at 40 and 45°C, P(n) was decreased, accompanied by an increase in substomatal CO(2) concentration (C(i)), decreases in stomatal conductance (g(s)) and the activation state of Rubisco, and inhibition of the donor side and the reaction center of PSII. The acceptor side of PSII was inhibited at 45°C but not at 40°C. When grape leaves recovered following heat treatment, P(n), g(s) and the activation state of Rubisco also increased, and the donor side and the reaction center of PSII recovered. The increase in P(n) during the recovery period following the second 45°C stress was slower than that following the 40°C stress, and these increases corresponded to the donor side of PSII and the activation state of Rubisco. CONCLUSIONS: Heat treatment at 35°C did not significantly (P>0.05) influence photosynthesis. The decrease of P(n) in grape leaves exposed to more severe heat stress (40 or 45°C) was mainly attributed to three factors: the activation state of Rubisco, the donor side and the reaction center of PSII. However, the increase of P(n) in grape leaves following heat stress was also associated with a stomatal response. The acceptor side of PSII in grape leaves was responsive but less sensitive to heat stress.
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Calor , Fotosíntesis/fisiología , Hojas de la Planta/fisiología , Vitis/fisiología , Dióxido de Carbono/metabolismo , Clorofila/metabolismo , Transporte de Electrón , Activación Enzimática , Fluorescencia , Complejo de Proteína del Fotosistema I/metabolismo , Complejo de Proteína del Fotosistema II/metabolismo , Hojas de la Planta/enzimología , Estomas de Plantas/enzimología , Estomas de Plantas/fisiología , Ribulosa-Bifosfato Carboxilasa/metabolismo , Vitis/enzimologíaRESUMEN
Two of the classical kallikrein genes KLK3 and KLK2 on 19q13.4 are plausible candidates in prostate cancer susceptibility. They are expressed almost exclusively in prostate tissue. We have performed a comprehensive analysis of association of variants in these two genes with prostate cancer among men of European descent using a tagging SNP approach. Thirteen SNPs selected from the HapMap database were analyzed in a sample of 596 histologically verified prostate cancer cases and 567 ethnically matched controls. Five SNPs showed significant association at single marker level. Linkage disequilibrium (LD) analysis revealed four LD blocks. We performed a haplotype analysis within each LD block. A major haplotype in block 1 that contains the first two significantly associated SNPs was significantly underrepresented in the prostate cancer cases; a second haplotype in block 3 also showed significant frequency differences between cases and controls. Four of the studied SNPs show positive associations with serum PSA levels. A structure analysis revealed no population stratification in our samples that could have confounded the association results. These findings suggest a plausible role of kallikrein gene variants in the etiology of prostate cancer among men of European ancestry.
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Cromosomas Humanos Par 19/genética , Polimorfismo de Nucleótido Simple , Antígeno Prostático Específico/genética , Neoplasias de la Próstata/genética , Calicreínas de Tejido/genética , Anciano , Alelos , Estudios de Casos y Controles , ADN de Neoplasias/genética , Frecuencia de los Genes , Haplotipos , Humanos , Desequilibrio de Ligamiento , Masculino , Antígeno Prostático Específico/sangre , Neoplasias de la Próstata/sangre , Población Blanca/genéticaRESUMEN
There is considerable evidence that genetic factors are involved in prostate cancer susceptibility. We have studied the association of 11 single nucleotide polymorphisms (SNPs) in the HEPSIN gene (HPN) with prostate cancer in men of European ancestry. HPN is a likely candidate in prostate cancer susceptibility, as it encodes a transmembrane cell surface serum protease, which is overexpressed in prostate cancer; HPN is also located on 19q11-q13.2, where linkage is found with prostate cancer susceptibility. In this case-control association study (590 men with histologically verified prostate cancer and 576 unrelated controls, all of European descent), we find significant allele frequency differences between cases and controls at five SNPs that are located contiguously within the gene. A major 11-locus haplotype is significantly associated, which provides further support that HPN is a potentially important candidate gene involved in prostate cancer susceptibility. Association of one of the SNPs with Gleason score is also suggestive of a plausible role of HPN in tumor aggressiveness.
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Predisposición Genética a la Enfermedad , Polimorfismo de Nucleótido Simple , Neoplasias de la Próstata/genética , Serina Endopeptidasas/genética , Población Blanca/genética , Estudios de Casos y Controles , Frecuencia de los Genes , Haplotipos , Humanos , Masculino , Neoplasias de la Próstata/patologíaRESUMEN
There are no reports on DNA sequences of hepatitis B virus (HBV) strains from Tibet, although this highland area has a high HBsAg-positive population. We characterized HBV isolates from sera of 26 HBsAg-positive Tibetans. To determine the HBV genotypes and their phylogenetic relationships, we sequenced two genomic regions, one including the pre-S1/pre-S2/S region and the other including the pre-C/C region. The sequences were classified into two different genotypes based on different regions of the genome, except for one isolate. To clarify this finding, two complete HBV genomes that represented the two groups of isolates were sequenced. From the sequencing results, we concluded that HBV strains in Tibet may be classified as genotype C, and there are at least two subgroups. The dominant subgroup is a C/D hybrid with serotype ayw2, and the other is genotype C with serotype adw. This is the first report of complete nucleotide sequences of HBV from Tibet. These results contribute to the investigation of recombinant HBV strains throughout the world and should encourage further study of genotypes and recombination in HBV from this particular region.
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Virus de la Hepatitis B/genética , Secuencia de Aminoácidos , Genotipo , Hepatitis B/sangre , Hepatitis B/virología , Virus de la Hepatitis B/clasificación , Humanos , Datos de Secuencia Molecular , Filogenia , Recombinación Genética , Serotipificación , TibetRESUMEN
The study of genomic divergence between humans and primates may provide insight into the origins of human beings and the genetic basis of unique human traits and diseases. Chromosome 21 is the smallest chromosome in the human genome, and some of its regions have been implicated in mental retardation and other diseases. In this study, we sequenced the coding and regulatory regions of 127 known genes on human chromosome 21 in DNA samples from human and chimpanzees and a part of the corresponding genes from orangutan, gorilla, and macaque. Overall, 3,003 nucleotide differences between human and chimpanzee were identified over approximately 400 kb. The differences in coding, promoter, and exon-intron junction regions were 0.51 +/- 0.02%, 0.88 +/- 0.03%, and 0.85 +/- 0.02%, respectively, much lower than the previously reported 1.23% in genomic regions, which suggests the presence of purifying selection. Significant variation in substitution rate among genes was observed by comparing the divergence between human and chimpanzee. Furthermore, by implementing a bioinformatics-based approach, we showed that the identification of genetic variants specific to the human lineage might lead to an understanding of the mechanisms that are attributable to the phenotypes that unique to humans, by changing the structure and/or dosage of the proteins expressed. A phylogenetic analysis unambiguously confirms the conclusion that chimpanzees were our closest relatives to the exclusion of other primates and the relative divergence of the Homo-Pan and that of (Homo-Pan)-Gorilla are 4.93 million years and 7.26 million years, respectively.