The mitochondrial tRNAAsp T7561C, tRNAHis C12153T and A12172G mutations may be associated with essential hypertension in a Han Chinese pedigree.

OBJECTIVES: Mutations in mitochondrial tRNA (mt-tRNA) are the important causes for maternally inherited hypertension, however, the pathophysiology of mt-tRNA mutations in clinical expression of hypertension remains poorly understood. MATERIAL AND METHODS: In this study, we report the molecular features of a Han Chinese pedigree with maternally transmitted essential hypertension. The entire mitochondrial genomes are PCR amplified and sequenced, Moreover, phylogenetic analysis, haplogroup analysis, as well as pathogenicity scoring system are used to assess the potential roles for mtDNA mutations. RESULTS: Strikingly, among ten matrilineal relatives, three of them suffer from variable degree of hypertension at different age at onset. Sequence analysis of the complete mitochondrial genomes suggests the presence of three possible pathogenic mtDNA mutations: tRNAAsp T7561C, tRNAHis C12153T and A12172G, together with a set of variants belonging to East Asian mitochondrial haplogroup M7a. Interestingly, the T7561C mutation occurs at position 44 in the variable region of tRNAAsp, while the C12153T and A12172G mutations are localized at extremely conserved nucleotides in the D-arm and anticodon stem of tRNAHis gene, respectively, which are critical for tRNA steady-state level and function. CONCLUSIONS: Mitochondrial T7561C, C12153T and A12172G mutations may lead to the failure in tRNAs metabolism, and cause mitochondrial dysfunction that is responsible for hypertension. However, the homoplasmy form of mt-tRNA mutations, incomplete penetrance of hypertension suggest that T7561C, C12153T and A12172G mutations are insufficient to produce the clinical phenotype, hence, other risk factors such as environmental factors, nuclear genes and epigenetic modifications may contribute to the phenotypic manifestation of maternally inherited hypertension in this Chinese pedigree.

Dynamic Simulation of Human Gait Model With Predictive Capability.

In this paper, it is proposed that the central nervous system (CNS) controls human gait using a predictive control approach in conjunction with classical feedback control instead of exclusive classical feedback control theory that controls based on past error. To validate this proposition, a dynamic model of human gait is developed using a novel predictive approach to investigate the principles of the CNS. The model developed includes two parts: a plant model that represents the dynamics of human gait and a controller that represents the CNS. The plant model is a seven-segment, six-joint model that has nine degrees-of-freedom (DOF). The plant model is validated using data collected from able-bodied human subjects. The proposed controller utilizes model predictive control (MPC). MPC uses an internal model to predict the output in advance, compare the predicted output to the reference, and optimize the control input so that the predicted error is minimal. To decrease the complexity of the model, two joints are controlled using a proportional-derivative (PD) controller. The developed predictive human gait model is validated by simulating able-bodied human gait. The simulation results show that the developed model is able to simulate the kinematic output close to experimental data.

Tumor promoting effect of circ_002172 associates with induced immune escape in breast cancer via the miR-296-5p/CXCL12 axis.

Comprehending the biology of tumorigenesis needs identification of determinants of the immune reaction during cancer development. This study intends to illustrate the mechanistic actions of a bioinformatically predicted circRNA circ_002172 in cytotoxic T lymphocytes (CTL) infiltration and escape of breast cancer (BC) from immunological destruction. Expression patterns of circ_002172, miR-296-5p, and CXCL12 were determined in BC tissues and cells. Effects of circ_002172, miR-296-5p, and CXCL12 on cell viability, migration, and invasion were examined through artificial modulation of their expression. The role of circ_002172 and CXCL12 on tumorigenesis was validated in subcutaneously transplanted and orthotopically transplanted tumors in nude mice. Upregulation of circ_002172 and CXCL12 and downregulation of miR-296-5p occurred in BC tissues and cells. Circ_002172 promoted the oncogenic phenotypes of BC cells in vitro and growth of tumors in vivo, which was reversed by knockdown of CXCL12 expression. Circ_002172, as a miR-296-5p sponge, upregulated expression CXCL12. Moreover, Ectopic expression of circ_002172 inhibited cytotoxic T lymphocytes (CTL) infiltration to promote the immune escape of BC. In conclusion, the tumor-promoting role of circ_002172 in BC was achieved by inducing immune escape via the miR-296-5p/CXCL12 axis.

MiR-6511b-5p suppresses metastasis of pMMR colorectal cancer through methylation of CD44 by directly targeting BRG1.

PURPOSE: Distal metastases are a major cause of poor prognosis in colorectal cancer patients. Approximately 95% of metastatic colorectal cancers are defined as DNA mismatch repair proficient (pMMR). Our previous study found that miR-6511b-5p was downregulated in pMMR colorectal cancer. However, the mechanism of miR-6511b-5p in pMMR colorectal cancer metastases remain unclear. METHODS: We first used quantitative real-time PCR to evaluate the role of miR-6511b-5p in colorectal cancer. Second, we conducted invasion assays and wound healing assays to investigate the role of miR-6511b-5p and CD44 in colorectal cancer cells metastases. Third, luciferase reporter assay, in situ hybridization (ISH), and immunohistochemistry assays were performed to study the relationship between miR-6511b-5p and BRG1. Finally, real-time quantitative PCR, immunohistochemistry, and chromatin immunoprecipitation (ChIP) assays were performed to analyze the relationship between BRG1 and CD44 in colorectal cancer. RESULTS: We found that lower expression of miR-6511b-5p appeared more often in pMMR colorectal cancer patients compared with dMMR (mismatch repair deficient) cases, and was positively correlated with metastases. In vitro, overexpression of miR-6511b-5p inhibited metastasis by decreasing CD44 expression via directly targeting BRG1 in colorectal cancer. Furthermore, BRG1 knockdown decreased the expression of CD44 by promoting CD44 methylation in colorectal cancer cells. CONCLUSION: Our data suggest that miR-6511b-5p may act as a promising biomarker and treatment target for pMMR colorectal cancer, particularly in metastatic patients. Mechanistically, miR-6511b-5p suppresses invasion and migration of colorectal cancer cells through methylation of CD44 via directly targeting BRG1.

Electrophilic Sulfonium-Promoted Peptide and Protein Amidation in Aqueous Media.

A novel amidation strategy using electrophilic sulfonium, which is soluble and stable in aqueous conditions, was developed. The sulfoniums could activate thioacid and carboxyl acid to efficiently react with amines to afford amides. This method enables applications in amidation in both aqueous media and solid-phase peptide synthesis, peptide/protein modifications, and reactive lysines of a proteome at pH 10 with activity-based protein profiling. A peptide ligand-directed labeling of the USP7-UBL2 domain was also performed using this method.

Histidine-specific bioconjugation via visible-light-promoted thioacetal activation.

Histidine (His, H) undergoes various post-translational modifications (PTMs) and plays multiple roles in protein interactions and enzyme catalyzed reactions. However, compared with other amino acids such as Lys or Cys, His modification is much less explored. Herein we describe a novel visible-light-driven thioacetal activation reaction which enables facile modification on histidine residues. An efficient addition to histidine imidazole N3 under biocompatible conditions was achieved with an electrophilic thionium intermediate. This method allows chemo-selective modification on peptides and proteins with good conversions and efficient histidine-proteome profiling with cell lysates. 78 histidine containing proteins were for the first time found with significant enrichment, most functioning in metal accumulation in brain related diseases. This facile His modification method greatly expands the chemo-selective toolbox for histidine-targeted protein conjugation and helps to reveal histidine's role in protein functions.

Hsa_circ_0000515 is a novel circular RNA implicated in the development of breast cancer through its regulation of the microRNA-296-5p/CXCL10 axis.

Cancer metastasis is a major cause of death among women afflicted with breast cancer (BC) and understanding the molecular processes involved is a major focus in BC research. Circular RNAs (circRNAs) have emerged as genomic regulatory molecules in carcinogenesis and metastasis; however, their role in BC is unclear. We characterized a novel circRNA, hsa_circ_0000515, in context of BC. We collected 340 cancerous tissues surgically resected from BC patients and found hsa_circ_0000515 was upregulated in BC tissues and associated with poor prognosis of BC. Silencing of hsa_circ_0000515 impaired cell cycle progression, cell proliferation, and invasion, attenuated inflammatory response, and reduced the proangiogenetic potential of BC cells. RNA pull-down and dual-luciferase reporter gene assays showed that hsa_circ_0000515 binds miR-296-5p, preventing it from repressing CXCL10 expression. We also observed that miR-296-5p inhibition or CXCL10 overexpression promoted cell cycle progression, restored proliferative, invasive and proangiogenetic abilities, and increased inflammatory response in MCF-7 cells in the absence of hsa_circ_0000515. In vivo analyses showed that partial loss of hsa_circ_0000515 reduced the tumor growth of MCF-7 cells in nude mice. The key findings from this study revealed that targeting hsa_circ_0000515 might be an effective strategy to combat BC.

Idiopathic pulmonary hemosiderosis in adults: review of cases reported in the latest 15 years.

BACKGROUND: Idiopathic pulmonary hemosiderosis (IPH) is a rare disorder of unknown etiology which can cause diffuse alveolar hemorrhage. IPH is found primarily in children. In adults, however, it is extremely rare. A systematic review was applied to identify the details of IPH in adults. METHODS: Articles of English or Chinese language published between 2000 and 2015 were included. Data were extracted on the clinical features, examinations, treatments and clinical outcome. RESULTS: A total of 37 cases of adult-onset IPH were included (13 females and 24 males). IPH combined with coeliac disease was found in five patients, three of whom received gluten-free diet (GFD) only and got full remission. Upon diagnosis, median age was 34 years. The main manifestations were: hemoptysis (n = 30, 81%), dyspnea (n = 23, 64%), anemia (n = 20, 54%). Most patients were treated by corticosteroids initially. The mortality rage was 14% on acute phase. CONCLUSION: The adult patients in this study showed some differences from the previously characterized IPH. It is characterized by immunologically mediated, middle-age onset, male dominance, absence of anemia, high mortality on acute phase.

Biophysical effects of pulsed lasers in the retina and other tissues containing strongly absorbing particles: shockwave and explosive bubble generation.

Damage by pulsed lasers to the retina or other tissues containing strongly absorbing particles may occur through biophysical mechanisms other than simple heating. Shockwaves and bubbles have been observed experimentally, and depending on pulse duration, may be the cause of retinal damage at threshold fluence levels. We perform detailed calculations on the shockwave and bubble generation expected from pulsed lasers. For a variety of different laser pulse durations and fluences, we tabulate the expected strength of the shockwave and size of the bubble that will be generated. We also explain how these results will change for absorbing particles with different physical properties such as absorption coefficient, bulk modulus, or thermal expansion coefficient. This enables the assessment of biological danger, and possible medical benefits, for lasers of a wide range of pulse durations and energies, incident on tissues with absorbing particles with a variety of thermomechanical characteristics.

Sweet potato starch residue as starting material to prepare polyacrylonitrile adsorbent via SI-SET-LRP.

Sweet potato starch residue (SPSR) was used as starting material to prepare an eco-friendly adsorbent. SPSR was modified by bromoacetyl bromide to obtain a macroinitiator for surface-initiated single electron transfer-living radical polymerization (SI-SET-LRP) of acrylonitrile (AN) catalyzed by La(0)/hexamethylenetetramine (HMTA) in N,N-dimethylformamide (DMF) in the presence of ascorbic acid (VC). The amidoxime (AO) adsorbent was prepared by the reaction of the graft copolymer bromoactylated sweet potato starch (BSPS)/polyacrylonitrile (BSPS-g-PAN) with hydroxylamine. The maximum adsorption capacity for Hg(II) was 4.03 mmol·g(-1). This simple method provided a novel approach to recycle and reuse agricultural residues for controlling heavy metal pollution.

Amputee Subject Testing Protocol, Results, and Analysis of a Powered Transtibial Prosthetic Device.

A powered ankle-foot prothesis and its control system were previously designed and built. To evaluate this prosthesis, amputee subject testing was performed. The testing results are analyzed and compared between the powered prosthesis, passive prosthesis, and able-bodied gait. Qualitative comparison showed the prosthesis achieved the design objectives. During stance phase, active ankle moment was generated in the powered prosthesis before push-off to help the amputee walk more naturally. During swing phase, the powered prosthesis was able to move to natural position to achieve foot clearance. However, the prosthesis is slightly under powered compared with the able-bodied ankle.

The emergence of chaos in a laser irradiated spherical absorber.

We show in this paper that the simple system of a spherical absorber immersed in water can exhibit complex and chaotic behavior upon absorption of laser energy. We report on computer experiments performed on this simple system. We present power spectra and calculate Lyapunov exponents that show that for increasing laser pulse durations and increasing laser energy the pressure response of the system changes from periodic to a regime displaying spatiotemporal chaos. This is important from a theoretical point of view because the complex behavior displayed in this simple system makes it an excellent choice for investigations into the nonlinear dynamics of fluids and the complicated transition to turbulence. This is also important for people using these systems for various applications in material science and biomedicine.