Alzheimer's disease (AD) is the most common type of cognitive impairment in the elderly. In this report, we presented a case of a 52-year-old woman with rapid disease progression within 6 months. She was diagnosed with mild dementia according to the clinical symptoms and neuropsychological assessment results. Based on the results of neuropathological proteins in cerebrospinal fluid, cranial magnetic resonance imaging, and positron emission tomography/computed tomography, the patient showed the presence of β amyloid deposition, pathologic tau along with neurodegeneration [A+T+(N+)], indicative of AD. Whole exome sequencing revealed a heterozygous C-to-T missense mutation of nucleotide 3,755 (c.3755C > T) in exon 25 of the angiotensin converting enzyme (ACE) gene on chromosome 17q23 (rs762056936).
Trace elements play important roles in human health, but little is known about their functions in humoral immunity. Here, we show an important role for iron in inducing cyclin E and B cell proliferation. We find that iron-deficient individuals exhibit a significantly reduced antibody response to the measles vaccine when compared to iron-normal controls. Mice with iron deficiency also exhibit attenuated T-dependent or T-independent antigen-specific antibody responses. We show that iron is essential for B cell proliferation; both iron deficiency and α-ketoglutarate inhibition could suppress cyclin E1 induction and S phase entry of B cells upon activation. Finally, we demonstrate that three demethylases, KDM2B, KDM3B and KDM4C, are responsible for histone 3 lysine 9 (H3K9) demethylation at the cyclin E1 promoter, cyclin E1 induction and B cell proliferation. Thus, our data reveal a crucial role of H3K9 demethylation in B cell proliferation, and the importance of iron in humoral immunity.
The methods of classification of chemical reactive hazards by maximum heat of decomposition,instantaneous power density and adiabatic reaction parameters were reviewed.A novel method of rating chemical reactive hazards based on experiment was presented,which used the criterions composed of onset temperature,heat of reaction and curve of detonation or deflagration.It is of important reference value to safety evaluation of chemicals.The reactive situations of six chemicals of organic peroxide were researched by accelerating rate calorimeter,and classified by the rating method.The hazards of reaction of organic peroxide were annotated,and the rationality of the rating method was validated.Combining the advantages of experiments and different methods could make the chemical reactive hazards rating method more practical.
Abstract Telomerase is expressed in adult mouse, but not in most human, tissues and mouse telomeres are much longer than those in humans. This interspecies difference of telomere homeostasis poses a challenge in modeling human diseases using laboratory mice. Using chromatinized bacterial artificial chromosome reporters, we discovered that the 5′ intergenic region, introns 2 and 6 of human telomerase gene ( hTERT ) were critical for regulating its promoter in somatic cells. Accordingly, we engineered a humanized gene, hmTert , by knocking-in a 47-kilobase hybrid fragment containing these human non-coding sequences into the mTert locus in mouse embryonic stem cells (mESCs). The hmTert gene, encoding the wildtype mTert protein, was fully functional, as a mESC line with homozygous hmTert alleles proliferated for over 400 population doublings without exhibiting chromosomal abnormalities. Like human ESCs, the engineered mESCs contained high telomerase activity, which was repressed upon their differentiation into fibroblast-like cells in a histone deacetylase-dependent manner. Fibroblast-like cells differentiated from these mESCs contained little telomerase activity. Thus, telomerase in mESCs with the hmTert alleles was subjected to human-like regulation. Our study revealed a novel approach to engineer a humanized telomerase gene in mice, achieving a milestone in creating a mouse model with humanized telomere homeostasis.
Animation can make the information and displays more engaging, vivid and more intuitively comprehended. The using animations to help learners understand and remember information has dramatically increased. A Flash animation or Flash cartoon is created using Flash animation software in the. swf file format [3]. It can be easily embedded in other application programs using Microsoft ActiveX technique. In addition, it also supports the action script language to interact with the third party or other programs. It is used to introduce the principle and workflow of NPP.
Serine protease inhibitor B7 (SERPINB7) mutations have been reported to cause Nagashima-type palmoplantar keratosis (NPPK), but their biological effects are largely unknown. We conducted whole-exome sequencing and identified a c.796C>T (p.Arg266Ter) mutation in SERPINB7 in a Chinese pedigree, which presented as an autosomal recessive inheritance pattern. We assessed the function of SERPINB7 in homozygous and heterozygous mutation carriers, and the results suggested that the single c.796C>T mutation may alter the subcellular localization of SERPINB7. One of the homozygous mutation patients (II-3) was treated with ixekizumab and showed moderate improvement in keratinization. In addition, we analysed the spatiotemporal expression of serpinb1l1 and serpinb1l3, the zebrafish homologue of human SERPINB7, which is expressed in larvae and adults. In larvae, both serpinb1l1 and serpinb1l3 were expressed in the digestive tract. Then, we performed RT-PCR on adult fins based on similarity to the site of NPPK expression in humans and found that the genes were expressed in five fins (pectoral, pelvic, dorsal, anal and caudal) of the zebrafish distal extremity. Taken together, our results demonstrated that the single c.796C>T (p.Arg266Ter) mutation may alter the location of SERPINB7-encoded protein in the skin, while zebrafish SERPINB7 homologue was expressed in adult fins. These findings will enable us to construct knock-out models to explore the pathogenesis of palmoplantar keratosis.
The present study aimed to investigate the effects of dietary pioglitazone hydrochloride (PGZ) and l-carnosine (LC) supplementation on the growth performance, meat quality, antioxidant status, and meat shelf life of yellow-feathered broiler chickens. Five hundred broiler chickens were randomly assigned into 4 experimental diets using a 2 × 2 factorial arrangement with 2 PGZ supplemental levels (0 and 15 mg/kg) and 2 LC supplemental levels (0 and 400 mg/kg) in basal diets for 28 d. The feed-to-gain ratio decreased whereas the average daily gain increased with PGZ supplementation. Greater dressing percentages, contents of intramuscular fat (IMF) in breast and thigh muscles, C18:3n-6, C18:1n-9 and monounsaturated fatty acid (MUFA) percentages of thigh muscle were observed with PGZ addition. Additionally, significant synergistic effects between PGZ and LC on the C18:1n-9 and MUFA contents were found. Supplementation with LC decreased drip loss, cooking loss and total volatile basic nitrogen, and increased the redness (a∗) value, the superoxide dismutase and glutathione peroxidase activities in thigh muscles. Moreover, the malondialdehyde content decreased when diets were supplemented with LC, and there was a synergistic effect between PGZ and LC. Additionally, the mRNA abundance of lipogenesis-related genes, such as peroxisome proliferator-activated receptor γ (PPARγ), PPARγ co-activator 1α and fatty acid-binding protein 3, increased with PGZ supplementation, and relevant antioxidation genes, such as nuclear factor erythroid-2-related factor 2 and superoxide dismutase 1, were enhanced with LC supplementation. In conclusion, the results indicated that the supplementation of PGZ and LC could improve the growth performance, antioxidant ability, IMF content, and meat shelf life of yellow-feathered broiler chickens.
This study's objective was to develop a method to evaluate the chaotic characteristic of alaryngeal speech. The proposed method will be capable of distinguishing between normal and alaryngeal voices, including esophageal (SE) and tracheoesophageal (TE) voices. It has been previously shown that alaryngeal voices exhibit chaotic characteristics due to the aperiodicity of their signals. The proposed method will be applied for future use to quantify both chaos behavior (CB) and the difference between SE and TE voices.A total of 74 voice recordings including 34 normal and 40 alaryngeal (26 SE and 14 TE) were used in the study. Voice samples were analyzed to distinguish alaryngeal voices from normal voices and to investigate different chaotic characteristics of SE and TE speech.A chaotic distribution detection-based method was used to investigate the CB of alaryngeal voices. This CB was used to detect the difference between SE and TE voice types. Quantification of the CB parameter was performed. Statistical analyses were used to compare the results of the CB analysis for both the SE and TE voices.Statistical analysis revealed that CB effectively differentiated between all normal and alaryngeal voice types (p < 0.01). Subsequent multiclass receiver operating characteristic (ROC) analysis demonstrated that CB (area under the curve) possessed the greatest classification accuracy relative to correlation dimension (D2).The CB metric shows strong promise as an accurate, useful metric for objective differentiation between all normal and alaryngaeal, SE and TE voice types. The CB calculations showed expected results, as SE voices have significantly more CB than TE voices, constituting substantial improvement over previous methods and becoming the first SE and TE classification method. This metric can help clinicians obtain additional acoustic information when monitoring the efficacy of treatment for patients undergoing total laryngectomies.
When the combat platform is running on the road at a constant speed, it will have different vibration responses due to the different speed and road roughness. Road excitation is the main vibration source of the vibration system of the combat platform. Obtaining accurate road information is the key to analyze and evaluate the impact of the combat platform system on the road. In this paper, based on the fitting expression of road power spectral density recommended by GB/T7031-2005 and Simulink simulation software, the simulation model of combat platform is established when it is moving, and then the time-domain response of 1/2 combat platform system dynamics model under road random excitation is analyzed. The influence of road roughness and running speed on the vibration response of platform body is analyzed. It provides a theoretical basis for the design and structure optimization of combat platform.
The mechanism for the basal targeting of the Miranda (Mira) complex during the asymmetric division of Drosophila neuroblasts (NBs) is yet to be fully understood. We have identified conserved Phosphotyrosyl Phosphatase Activator (PTPA) as a novel mediator for the basal localization of the Mira complex in larval brain NBs. In ptpa NBs, Mira remains cytoplasmic during early mitosis where its basal localization is delayed until anaphase. Detailed analyses indicate that PTPA acts independently of, and prior to, aPKC activity to localize Mira. Mechanistically, our data show that the phosphorylation status of the Thr591 (T591) residue determines the subcellular localization of Mira and that PTPA facilitates the dephosphorylation of T591. Furthermore, PTPA associates with the Protein Phosphatase 4 complex to mediate Mira localization. Based on these results, a two-step process for Mira basal localization during NB division is revealed where PTPA/PP4-mediated cortical association followed by apical aPKC-mediated basal restriction.
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