We previously conducted a systematic field synopsis of 1059 breast cancer candidate gene studies and investigated 279 genetic variants, 51 of which showed associations. The major limitation of this ...work was the small sample size, even pooling data from all 1059 studies. Thereafter, genome-wide association studies (GWAS) have accumulated data for hundreds of thousands of subjects. It's necessary to re-evaluate these variants in large GWAS datasets.
Of these 279 variants, data were obtained for 228 from GWAS conducted within the Asian Breast Cancer Consortium (24,206 cases and 24,775 controls) and the Breast Cancer Association Consortium (122,977 cases and 105,974 controls of European ancestry). Meta-analyses were conducted to combine the results from these two datasets.
Of those 228 variants, an association was observed for 12 variants in 10 genes at a Bonferroni-corrected threshold of P < 2·19 × 10−4. The associations for four variants reached P < 5 × 10−8 and have been reported by previous GWAS, including rs6435074 and rs6723097 (CASP8), rs17879961 (CHEK2) and rs2853669 (TERT). The remaining eight variants were rs676387 (HSD17B1), rs762551 (CYP1A2), rs1045485 (CASP8), rs9340799 (ESR1), rs7931342 (CHR11), rs1050450 (GPX1), rs13010627 (CASP10) and rs9344 (CCND1). Further investigating these 10 genes identified associations for two additional variants at P < 5 × 10−8, including rs4793090 (near HSD17B1), and rs9210 (near CYP1A2), which have not been identified by previous GWAS.
Though most candidate gene variants were not associated with breast cancer risk, we found 14 variants showing an association. Our findings warrant further functional investigation of these variants.
National Institutes of Health.
Abstract
Gasoline and diesel vehicles are one of the main sources of PMs generation which are harmful to human health and the environment. The light emitted from the headlights of these vehicles may ...cause to make the PMs more/less/not dangerous than the raw PMs to human health and the environment by changing their properties. However, there is no information available in this field. Therefore, this research is presented to investigate the effect of light emitted from one of the most common vehicle headlights (Halogen type) on the physical properties of PMs. Three PM samples taken directly from one diesel vehicle operating at an idle condition, and inside of a diesel particulate filter and gasoline vehicle exhaust pipe (engine was off) were exposed to the vehicle headlight for 6 hrs at 10 cm distance. It is observed that the vehicle light has the potential to change the structure, shape, and size of the PMs, while the fresh PMs from diesel vehicle receives more changes (43.5% increase in particle diameter) compared with the other two samples containing mature/aged PMs (increases of 3.6 and 9.9%, respectively). Also, the effect of the beam from the scanning electron microscope on the PM physical properties is presented.
The aim of this study was to examine the association of non-random X chromosome inactivation (XCI) and loss of heterozygosity (LOH) at Xq25 with breast cancer development.
Seventy-nine breast cancer ...patients, 39 female lung cancer patients, 30 other cancer patients and 77 healthy females were analysed for LOH using a panel of 11 microsatellite markers spanning Xq25. The androgen receptor (AR) gene was chosen as an XCI marker.
LOH of at least one microsatellite locus at Xq25 was identified in 46/65 breast cancers examined, while only 10/25 cancers of other origins demonstrated LOH in this region (p = 0.014). The critical deletion region in breast cancer was around marker DXS1047 (47.23%). Moreover, we found that tissues from eight breast cancers showed LOH at all of the informative loci tested at Xq25, while the other 38 showed partial (interstitial or telomeric) alterations at Xq25. Interestingly, the pattern of XCI of these eight breast cancers tended to be non-random. We estimated the frequencies of AR alleles and found that women with two long AR alleles (≥21 CAG repeats) had an increased risk of developing breast cancer, while those with two short AR alleles (<21 CAG repeats) were likely to be normal (p = 0.00069).
The extraordinary high frequencies of LOH at Xq25 found in this study strongly imply that there might be one or more tumour suppressor genes (TSGs) related to the development of breast cancer at Xq25 in the Taiwanese female population.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
DPP-IV is a prolyl dipeptidase, cleaving the peptide bond after the penultimate proline residue. It is an important drug target
for the treatment of type II diabetes. DPP-IV is active as a dimer, and ...monomeric DPP-IV has been speculated to be inactive.
In this study, we have identified the C-terminal loop of DPP-IV, highly conserved among prolyl dipeptidases, as essential
for dimer formation and optimal catalysis. The conserved residue His 750 on the loop contributes significantly for dimer stability. We have determined the quaternary structures of the wild type,
H750A, and H750E mutant enzymes by several independent methods including chemical cross-linking, gel electrophoresis, size
exclusion chromatography, and analytical ultracentrifugation. Wild-type DPP-IV exists as dimers both in the intact cell and
in vitro after purification from human semen or insect cells. The H750A mutation results in a mixture of DPP-IV dimer and monomer.
H750A dimer has the same kinetic constants as those of the wild type, whereas the H750A monomer has a 60-fold decrease in
k cat . Replacement of His 750 with a negatively charged Glu (H750E) results in nearly exclusive monomers with a 300-fold decrease in catalytic activity.
Interestingly, there is no dynamic equilibrium between the dimer and the monomer for all forms of DPP-IVs studied here. This
is the first study of the function of the C-terminal loop as well as monomeric mutant DPP-IVs with respect to their enzymatic
activities. The study has important implications for the discovery of drugs targeted to the dimer interface.
What’s known on the subject? and What does the study add?
It has been known that there is an increase of oxidative damage in the bladder tissues of animals after PBOO. However, no reliable oxidative ...stress biomarkers in either urine or plasma have been available for the assessment of the severity of PBOO.
This study clearly demonstrated that the levels of oxidative stress biomarkers are increased in urine and plasma of the rabbits with PBOO.
OBJECTIVE
•
To investigate oxidative stress and oxidative damage biomarkers in urine and plasma after partial bladder outlet obstruction (PBOO) in rabbits.
MATERIALS AND METHODS
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In all, 16 male New Zealand White rabbits were separated equally into four groups: a control group and PBOO‐treated groups for 2, 4 and 8 weeks.
•
The oxidative stress biomarkers assessed included urinary 8‐hydroxy‐2′‐deoxyguanosine (8‐OHdG) and plasma malondialdehyde (MDA).
•
We also measured the total antioxidant capacity (TAC) in blood plasma.
•
8‐OHdG, MDA and TAC were measured at both the beginning and indicated time points of the experimental design.
RESULTS
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There was no significant difference in body weight among rabbits in the four groups.
•
However, there was a significant increase in bladder weight after 2 weeks of PBOO. After 4 and 8 weeks of PBOO, there was an additional significant increase in bladder weight in all three groups.
•
There was no difference in blood creatinine levels among the groups.
•
In the 4‐ and 8‐week PBOO groups, there was a significant increase of 8‐OHdG in urine and of MDA in plasma, while there was a significant decrease in TAC in plasma.
CONCLUSION
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The results showed that oxidative stress could be detected in the plasma and urine of rabbits after 4 and 8 weeks of PBOO, and not only from bladder tissue as previously reported. Thus, there could be an easy and alternative way to evaluate bladder function by analysis of urine and/or plasma.
•
Additionally, rabbits with chronic PBOO showed an increase in systemic oxidative stress, which could be a novel starting point for examining the link between the lower urinary tract symptoms/benign prostate hyperplasia and metabolic syndrome in future studies.
Japanese Neologisms in Chinese Schmidt, Christian; Chen, Chien-shou
Lexicography (Berlin),
06/2022, Letnik:
9, Številka:
1
Journal Article
Recenzirano
Japanese loanwords in Chinese are currently not accepted as legitimate loanwords in the general loanword framework (Haspelmath and Tadmor, 2009a), mainly because they are considered to be graphic ...loans (Masini, 1997; Tranter, 2009) and not sound-meaning borrowings. This paper formulates a counterargument, developed mainly from the perspective of the Chinese scholarship: it focuses on how graphemic borrowing impacts the judgment of loanwordness and the types of resolving strategies that have been developed. The origin of word form, word meaning, and the pathways of historical borrowing particularly stand out as non-linguistic factors of loanwordness. Based on a metaanalysis of 25 studies of Japanese loanwords in Chinese, the authors propose a typology of Japanese loanwords in Chinese that bridges the Western and the Chinese frameworks. To put forward a concrete example, we compile a list of 2,920 Japanese loanwords in Chinese, which are discussed by at least three scholars, ordered by degrees of agreement within the Chinese scholarship. We compare this list against the vocabulary list of the World Loanword Database and demonstrate that Wiebusch and Tadmor (2009), in ignoring Japanese loanwords, also omits numerous loanwords in Chinese. We echo Tranter (2009) in arguing that Japanese loanwords in Chinese can be classified as material borrowing, putting graphemic borrowing on the same footing with phonetic borrowing, since graphemic borrowing is not limited to, though preferred by, the Chinese writing system. We demonstrate this by comparing how writing systems impact borrowing.
Intensity modulated radiotherapy (IMRT) beams may have strong fluence variations and are advantageous at disease sites such as lung and head and neck (H&N), where neighboring tissues have very ...different electron densities. We use Monte Carlo (MC) dose calculations to evaluate the dosimetric effects of these inhomogeneities for 10 clinical IMRT treatment plans for five lung patients and four H&N patients. All beams are 6 MV photons. “Standard plans” were first produced on a clinical treatment planning system which optimizes beam intensity distributions to meet dose and dose-volume constraints and calculates dose using a measurement-based pencil-beam algorithm with an equivalent pathlength inhomogeneity correction. Patient anatomy and electron densities were obtained from patient-specific CT images. The dose distribution of each beam was recalculated with the MC method, using the same CT images, beam geometry, beam weighting and optimized fluence intensity distributions as the corresponding standard plan. For the lung cases, the MC calculated dose distributions are characterized by reduced penetrations and increased penumbra due to larger secondary electron range in the low-density media, which is not accurately accounted for in the pencil beam algorithm. For the lung cases, the PTV was underdosed; except for one dose-volume index, underdose was less than 10%. Individual H&N fields are affected to different degrees by tissue inhomogeneities, depending on specific anatomy, especially the size and location of air cavities in relation to the beam orientation and field size. For four H&N plans, PTV coverage changed by less than 2%; for the fifth, there was less than 10% difference between the standard and the MC plans. Critical normal tissue DVHs (cord, lung, brainstem) are changed by <10% at the high dose end and mean lung doses are changed by <6%.
In this paper, we study a consumption, investment and life insurance strategy model in which agent has time-inconsistent preferences. We numerically find that time-inconsistent preferences lead agent ...to more consumption-wealth ratio and less insurance-wealth ratio, and that time-inconsistent agent purchases life insurance in advance. Moreover, both the consumption-wealth ratio and amount of life insurance purchased for naive agent are less than for sophisticated one, while total available wealth for naive agent is more than for sophisticated one. In particular, total amount of life insurance purchased increases when agent is young, but the situation reverses when she is older.
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