During the first 6 years of the Program of Genetic Counselling in Cancer of Valencia (eastern Spain), 310 mutations (155 in
BRCA1
and 155 in
BRCA2
) in 1,763 hereditary breast (BC) and ovarian cancer ...(OC) families were identified. Of the mutations found 105 were distinct (53 in
BRCA1
and 52 in
BRCA2
), eight new and 37 recurrent. Two of the novel mutations were frame-shift placed in exons 2 and 11 of
BRCA1
and the remaining six were placed in
BRCA2
; four frame-shift (three in exon 11 and one in exon 23), one deletion of the entire exon 19 and one in the intervening sequence of exon 22. The
BRCA1
mutations with higher recurrence were c.66_68delAG, c.5123C > A, c.1961delA, c.3770_3771delAG and c.5152+5G > A that covered 45.2 % of mutations of this gene. The age of onset of BCs of c.68_69delAG mutation carriers occurs later than for the other recurrent mutations of this gene (45 vs. 37 years;
p
= 0.008). The
BRCA2
mutations with higher recurrence were c.9026_9030delATCAT, c.3264insT and c.8978_8991del14 which represented 43.2 % of all mutations in this gene, being the most recurrent mutation by far c.9026_9030delATCAT that represents 21.3 % of
BRCA2
mutations and 10.6 % of all mutations. Probands with family histories of BC and OC, or OC and/or BC in at least two first degree relatives, were the more likely to have
BRCA1/BRCA2
mutations (35.2 % of the total mutations). And that most
BRCA1
mutations (73.19 % mutations) occurred in probands with early-onset BC or with family history of OC.
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•A novel LC–MS method using hybrid full scan and MRM was developed.•29 saponins in different architectural components of IFO and IFU were quantified.•Flower bud has the highest ...abundance of the summed saponins.•Fruit pedicel and pericarp, the useless by-products of seed processing, have the abundant saponins.•The summed contents in 3-year-old plants were higher than those in 2-year-old ones.
The roots of Panax notoginseng (Burk) F. H. Chen are used as a highly valuable Chinese herbal medicine in the prevention and treatment of cardiovascular and hematological diseases. Several aerial parts of plant are usually abandoned as the wastes. Panax notoginseng inflorescence (IFO) is commonly used as a folk medicine and dietary ingredient, its fruiting stage is referred as infructescence (IFU). Owing to high chemical complexity and structural similarity of ginsenosides, the co-eluting phenomenon, especially for the isomers, is inevitable in the chromatogram, resulting in the inaccurate quantitation. A novel LCMS method using hybrid positive full scan and multiple reaction monitoring (MRM) modes was developed to characterize ginsenoside distribution in different architectural components of IFO and IFU. MRM was performed for the quantification of G-Ra2 and NG-Fp2, a pair of co-eluting isomers with identical negative MS and MS/MS characteristics, and full scan was conducted to quantify other investigated saponins. Our data indicate that flower buds have the highest abundance of the summed saponins, fruit pedicel and fruit pericarp, commonly considered as the useless by-products of seed processing, contain the abundant saponins. Additionally, the contents of the detected ginsenosides in these architectural components significantly increased along with their growth years. Our findings will facilitate comprehensive utilization and exploitation of P. notoginseng inflorescence and infructescence.
We report the effects of single-layer different bags with different colour (white, yellow, yellow outside and black inside) and double-layer bag (yellow outside and black inside) on several fruit ...quality traits of ‘Ruiguang 47’ nectarine. Fruit (x20 a treatment) were bagged from day 40 after full bloom till harvest, while the yellow/black bags were removed 4 days before harvest. Bagged fruit tend to have earlier ripening and higher fruit weight (white and yellow bag). Fruit treated by yellow/black bags had better colour, anthocyanin content and anthocyanin to chlorophyll ratio (Ant/Chl). Soluble solids content (SSC) was not significantly affected by white and yellow bags but it reduced significantly when treated with yellow/black. In addition, fruit firmness with and without skin of white and yellow bag treatments decreased significantly while increased with yellow outside and black inside single layer bag. In regard to fruit treated by yellow outside and black inside double-layer bag, skin firmness improved significantly in 2011 but had no significant differences in 2012. The results indicate that bagging of ‘Ruiguang 47’ nectarine in white bag can keep better quality. However, removing yellow/black bags 4 days before harvest can improve skin colour and increase fruit firmness.
Highlights • We use systematic strategy and broad search terms in multiple databases and websites. • We use rigorous methods to extract and appraise the data. • Both clinical trials and ...post-marketing observations are included to analyze. • MMRV vaccine increases potential risk of febrile seizure during second observed week. • We provide evidence-based knowledge of febrile seizure risk after MMRV vaccine.
Herpesviruses (HVs) can cause asymptomatic, benign, or fatal infections in a variety of animal species. However, the prevalence and phylogenetic characteristics of HVs in rodents and shrews in China ...are poorly understood. We thus performed a molecular detection and phylogenetic analysis of rat and shrew HVs in southern China between 2012 and 2014. Seventeen (6.7%) of 255 rectal swab specimens from rats and six (6.7%) of 90 rectal swab specimens from shrews tested positive for HVs. Phylogenetic analysis revealed that rodent and shrew HVs detected in this study were species specific, clustering in the Betaherpesvirinae and Gammaherpesvirinae clade. Novel Macavirus was detected in Rattus norvegicus (RN/13YX52/24 and RN/14HC50) and gammaherpesviruses in Suncus murinus (SM/14BY7/16/20/97/99/106).These findings have contributed to our understanding of the taxonomy, phylogeny, and biology of HVs.
Panax notoginseng inflorescences (PNI) and leaves (PNL) are commonly used as folk medicine and food supplements. In this study, an online two-dimensional hydrophilic interaction × reversed-phase ...liquid chromatography coupled to linear trap quadropole mass spectrometry method was developed to determine 24 ginsenosides, including two novel compounds, in PNI and PNL extracted by water and methanol. Our data demonstrated that ginsenosides Rd, Rc, Rb2, Rb3, Rb1, Ra2, Ra1, and Ra3 in both PNI and PNL extracted by water rather than methanol can be transformed to ginsenoside F2, notoginsenoside Fe, ginsenoside Rd2, notoginsenoside Fd, gypenoside XVII, PN02, PN01, and PN03, respectively, by selectively cleaving the β-(1→2)-glucosidic linkage at the C-3 position. Ginsenoside transformation was further verified to be mediated by the proteins isolated from samples. Additionally, the two newly discovered transformed products, namely, PN02 and PN03, were prepared and identified as novel compounds by nuclear magnetic resonance. Our findings provide new insight into the importance of extraction solvents on the component profile of natural products.
Several novel adenoviruses (AdVs) have recently been identified in humans and other animal species. In this study, we report the molecular detection of and phylogenetically characterize bat and human ...AdVs detected in fecal or rectal swab samples collected in southern China. To detect AdVs, a 252-261 bp fragment of the DNA polymerase (DPOL) gene was amplified using nested PCR. A total of 520 rectal swab samples were collected from eight bat species in four geographic regions of southern China (Guangzhou, Yunfu, Huizhou, and Haikou city). Thirty-six (6.9%) samples from the following species tested positive for AdVs: Myotis ricketti, Miniopterus schreibersii, Scotophilus kuhlii, Taphozous melanopogon, Rhinolophus blythi, and Cynopterus sphinx. Eight novel AdVs were detected in 13.3% of the samples from C. sphinx. Of 328 fecal samples from patients with diarrhea, 16 (4.9%) were positive for classical human AdVs. Phylogenetic analysis showed that human AdVs shared low similarity (57.1-69.3%) with bat AdVs in deduced amino acid sequences of the AdV DPOL region. Thus, our study indicated that bat AdVs and human AdVs are species specific. As such, there is no evidence of cross-species transmission of AdV between bats and humans based on current data.
Aluminum-lithium (Al–Li) alloys have become an essential material for aircraft skin in the aerospace industry owing to their high strength and low density. An optimized coherent Cu/Li ratio and well ...controlled precipitation sequence are critical to upgrade the desired properties. In this study, we systematically evaluate the effect of the Cu/Li ratio (ranging from 0.5 to 1.4) on the aging hardening and precipitation behavior of Al–Cu–Li alloys with specific rare earth elements (Sc, Zr, and Ce). Using state-of-the-art aberration-corrected transmission electron microscopy equipped with super-energy-dispersive X-ray spectroscopy (EDS) and atomic scale spatially resolved electron energy loss spectroscopy (EELS) with K3 camera, classical strengthening phases, such as Cu containing precipitates T1 (Al2CuLi), θ′ (Al2Cu) and Li-rich phase δ′ (Al3Li), have been identified during the artificial aging and natural aging treatment. A new Li-rich phase (namely, the GP-Li zone) with a hexagonal shape has been identified in alloys with Cu/Li ratios of 0.5 and 1. High density GP-Li zones are formed after five months natural aging, which are found fully coherent with the Al matrix. The discovery of GP-Li zones shows a new precipitation path for Li atoms in the supersaturated solid solution. Besides, the GP-Li zone stimulates the nucleation of T1 and θ′ phase at the interfaces indicating that there is an alternative approach for the nucleation mechanism of T1 and θ′. The crossover between the suppression of δ′ phase formation and the acceleration of T1 and θ′ precipitation occurs when the Cu/Li ratio is increased during the artificial aging process, resulting in a decrease in the aging hardening ability at first, followed by a large recovery in aging hardening. The findings of this study provide a strategy to design high strength Al–Li alloys through the manipulation of Cu/Li ratios and the newly identified GP-Li phase.
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To exploit the biological and pharmacological properties of immunoglobulin constant domain Fc fragment and increase the killing efficacy of T cells, a single chain variable fragment specific to CD3 ...was fused with Fcab (Fc antigen binding), a mutant Fc fragment with specificity against Human epidermal growth factor receptor 2 (HER2) developed by F-star. The bispecific fusion named as FcabCD3 was expressed by transient transfection in HEK-293T cells and purified by affinity chromatography. Specific cytolytic activity of retargeted T cells to kill HER2 positive SKBR3 cell line was evaluated in vitro. FcabCD3 was able to retarget T cells to kill both Herceptin insensitive Colo205-luc cell line and HER2 low expression MDA-MB-231-luc cell line. Furthermore, FcabCD3 was effective in eliminating the Colo205 tumor established on BALB/c nu/nu mice.
LZ-8, an immunomodulatory protein isolated from Ganoderma lucidum (also known as Ling-Zhi or Reishi), has been shown to promote cell proliferation and IL-2 production in T cells. In this study, we ...show that LZ-8 induces the expansion of both murine and human CD4+ T cells into FOXP3+ regulatory T (Treg) cells. LZ-8 treatment was found to stimulate a 4-fold and a 10-fold expansion in the Treg populations of murine and human primary CD4+ T cells, respectively. In addition, the expression of CTLA-4 and IL-10 was induced in LZ-8-treated CD4+ T cells. Using neutralizing antibodies and gene-deficient T-cell lines, we also found that LZ-8 promotes Treg expansion through a CD45-mediated signaling pathway and that the CD18-dependent induction of IL-2 was involved in Treg formation and IL-10 production. The suppressive activity of LZ-8 was confirmed using a murine model of DSS-induced colitis; the disease was alleviated by the adoptive transfer of LZ-8-treated CD4+ T cells. In conclusion, a new regulatory function for LZ-8 was identified, and the molecular mechanisms underlying this function were elucidated.
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