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On page 472 showing 9421 ~ 9440 papers out of 2,794,544 papers

A Strain-Based Method to Estimate Tire Parameters for Intelligent Tires under Complex Maneuvering Operations.

  • Mª Fernanda Mendoza-Petit‎ et al.
  • Sensors (Basel, Switzerland)‎
  • 2019‎

The possibility of using tires as active sensors opens the door to a huge number of different ways to accomplish this goal. In this case, based on a tire equipped with strain sensors, also known as an Intelligent Tire, relevant vehicle dynamics information can be provided. The purpose of this research is to improve the strain-based methodology for Intelligent Tires to estimate all tire forces, based only on deformations measured in the contact patch. Firstly, through an indoor test rig data, an algorithm has been developed to pick out the relevant features of strain data and correlate them with tire parameters. This information of the tire contact patch is then transmitted to a fuzzy logic system to estimate the tire parameters. To evaluate the reliability of the proposed estimator, the well-known simulation software CarSim has been used to back up the estimation results. The software CarSim has been used to provide the vehicle parameters in complex maneuvers. Finally, the estimations have been checked with the simulation results. This approach has enabled the behaviour of the intelligent tire to be tested for different maneuvers and velocities, providing key information about the tire parameters directly from the only contact that exists between the vehicle and the road.


Prevalence and Risk Factors for Undiagnosed Glucose Intolerance Status in Apparently Healthy Young Adults Aged <40 Years: The Korean National Health and Nutrition Examination Survey 2014-2017.

  • Young Sang Lyu‎ et al.
  • International journal of environmental research and public health‎
  • 2019‎

Background: Early-onset diabetes results in longer lifetime hyperglycemic exposure that consequently leads to earlier chronic diabetes complications and premature death. The aim of this study was to quantify the prevalence and risk factors of undiagnosed diabetes and undiagnosed prediabetes in apparently healthy young adults aged <40 years. Methods: This study used data from the Korean National Health and Nutrition Examination Survey, a cross-sectional, nationally representative survey conducted by the Korean Ministry of Health and Welfare from 2014 to 2017. A total of 4442 apparently healthy young adults enrolled in this study. Multivariate logistic regression analyses were conducted separately to evaluate associated risk factors with undiagnosed diabetes and undiagnosed prediabetes in groups stratified by sex. Results: The prevalence of undiagnosed diabetes and undiagnosed prediabetes was 1.2% and 25.0%, respectively. Obesity (body mass index ≥ 30.0 kg/m2) was a significant risk factor of undiagnosed diabetes regardless of sex (men, odds ratio (OR): 9.808, 95% confidence interval (CI): 1.619-59.412; women, OR: 7.719, 95% CI: 1.332-44.747). Family history of diabetes was significantly associated with undiagnosed diabetes (OR: 3.407, 95% CI: 1.224-9.481) in women only. Increased age, obesity status, and family history of diabetes were significant risk factors for undiagnosed prediabetes. Alcohol consumption was found to be negatively associated with undiagnosed prediabetes in women. Conclusions: Increased attention and implementation of precise strategies for identifying young adults at high risk for undiagnosed diabetes would allow for increased wellbeing as well as reduced healthcare burdens associated with diabetes.


Insulin Treatment Forces Arteriogenesis in Diabetes Mellitus by Upregulation of the Early Growth Response-1 (Egr-1) Pathway in Mice.

  • Senthilkumar Thulasingam‎ et al.
  • International journal of molecular sciences‎
  • 2019‎

The process of arteriogenesis is severely compromised in patients with diabetes mellitus (DM). Earlier studies have reported the importance of Egr-1 in promoting collateral outward remodeling. However, the role of Egr-1 in the presence of DM in outward vessel remodeling was not studied. We hypothesized that Egr-1 expression may be compromised in DM which may lead to impaired collateral vessel growth. Here, we investigated the relevance of the transcription factor Egr-1 for the process of collateral artery growth in diabetic mice. Induction of arteriogenesis by femoral artery ligation resulted in an increased expression of Egr-1 on mRNA and protein level but was severely compromised in streptozotocin-induced diabetic mice. Diabetes mellitus mice showed a significantly reduced expression of Egr-1 endothelial downstream genes Intercellular Adhesion Molecule-1 (ICAM-1) and urokinase Plasminogen Activator (uPA), relevant for extravasation of leukocytes which promote arteriogenesis. Fluorescent-activated cell sorting analyses confirmed reduced leukocyte recruitment. Diabetes mellitus mice showed a reduced expression of the proliferation marker Ki-67 in growing collaterals whose luminal diameters were also reduced. The Splicing Factor-1 (SF-1), which is critical for smooth muscle cell proliferation and phenotype switch, was found to be elevated in collaterals of DM mice. Treatment of DM mice with insulin normalized the expression of Egr-1 and its downstream targets and restored leukocyte recruitment. SF-1 expression and the diameter of growing collaterals were normalized by insulin treatment as well. In summary, our results showed that Egr-1 signaling was impaired in DM mice; however, it can be rescued by insulin treatment.


Dynamics and Mechanisms in the Recruitment and Transference of Histone Chaperone CIA/ASF1.

  • Yanjun Zhang‎ et al.
  • International journal of molecular sciences‎
  • 2019‎

The recruitment and transference of proteins through protein-protein interactions is a general process involved in various biological functions in cells. Despite the importance of this general process, the dynamic mechanism of how proteins are recruited and transferred from one interacting partner to another remains unclear. In this study, we investigated the dynamic mechanisms of recruitment and translocation of histone chaperone CIA/ASF1 for nucleosome disassembly by exploring the conformational space and the free energy profile of unbound DBD(CCG1) and CIA/ASF1-bound DBD(CCG1) systems through extensive molecular dynamics simulations. It was found that there exists three metastable conformational states for DBD(CCG1), an unbound closed state, a CIA/ASF1-bound half-open state, and an open state. The free energy landscape shows that the closed state and the half-open state are separated by a high free energy barrier, while the half-open state and the open state are connected with a moderate free energy increase. The high free energy barrier between the closed and half-open states explains why DBD(CCG1) can recruit CIA/ASF1 and remain in the binding state during the transportation. In addition, the asymmetric binding of CIA/ASF1 on DBD(CCG1) allows DBD(CCG1) to adopt the open state by moving one of its two domains, such that the exposed domain of DBD(CCG1) is able to recognize the acetylated histone H4 tails. As such, CIA/ASF1 has a chance to translocate from DBD(CCG1) to histone, which is also facilitated by the moderate energy increase from the bound half-open state to the open state of DBD(CCG1). These findings suggest that the recruitment and transference of histone chaperone CIA/ASF1 is highly favored by its interaction with DBD(CCG1) via conformational selection and asymmetric binding, which may represent a general mechanism of similar biological processes.


Antimicrobial and Conductive Nanocellulose-Based Films for Active and Intelligent Food Packaging.

  • Carla Vilela‎ et al.
  • Nanomaterials (Basel, Switzerland)‎
  • 2019‎

Bacterial nanocellulose (BNC) is becoming an important substrate for engineering multifunctional nanomaterials with singular and tunable properties for application in several domains. Here, antimicrobial conductive nanocomposites composed of poly(sulfobetaine methacrylate) (PSBMA) and BNC were fabricated as freestanding films for application in food packaging. The nanocomposite films were prepared through the one-pot polymerization of sulfobetaine methacrylate (SBMA) inside the BNC nanofibrous network and in the presence of poly(ethylene glycol) diacrylate as cross-linking agent. The ensuing films are macroscopically homogeneous, more transparent than pristine BNC, and present thermal stability up to 265 °C in a nitrogen atmosphere. Furthermore, the films have good mechanical performance (Young's modulus ≥ 3.1 GPa), high water-uptake capacity (450-559%) and UV-blocking properties. The zwitterion film with 62 wt.% cross-linked PSBMA showed bactericidal activity against Staphylococcus aureus (4.3-log CFU mL-1 reduction) and Escherichia coli (1.1-log CFU mL-1 reduction), and proton conductivity ranging between 1.5 × 10-4 mS cm-1 (40 °C, 60% relative humidity (RH)) and 1.5 mS cm-1 (94 °C, 98% RH). Considering the current set of properties, PSBMA/BNC nanocomposites disclose potential as films for active food packaging, due to their UV-barrier properties, moisture scavenging ability, and antimicrobial activity towards pathogenic microorganisms responsible for food spoilage and foodborne illness; and also for intelligent food packaging, due to the proton motion relevant for protonic-conduction humidity sensors that monitor food humidity levels.


Comparison of the Aroma Profiles of Intermediate Wheatgrass and Wheat Bread Crusts.

  • Laurianne Paravisini‎ et al.
  • Molecules (Basel, Switzerland)‎
  • 2019‎

The aroma profiles of bread crusts made from intermediate wheatgrass (Thinopyrum intermedium) and whole wheat (Triticum aestivum) flours were compared. Based on gas chromatography/mass spectrometry/olfactometry analysis, twenty-four odorants were identified and further quantified. The concentrations of seventeen compounds were significantly different between intermediate wheatgrass and whole wheat bread crusts, of which sixteen compounds were higher in the whole wheat sample. The aroma profiles of the bread samples were subsequently characterized using sensory descriptive analysis (DA) and indicated that the roasted attribute was perceived at a significantly higher intensity in the whole wheat sample due to a greater amount of Maillard reaction compounds. Alternatively, bran and green notes were perceived at higher intensities in the intermediate wheatgrass sample, however they were not attributed to the presence of specific compounds but rather to a change in the aroma composition. Aroma recombination DA of the whole wheat and intermediate wheatgrass aroma models was similar to the original aroma profiles of the bread samples, demonstrating the sensory relevance of the identified odorants.


Profiling the Stromal and Vascular Heterogeneity in Patient-derived Xenograft Models of Head and Neck Cancer: Impact on Therapeutic Response.

  • Margaret Folaron‎ et al.
  • Cancers‎
  • 2019‎

Head and neck squamous cell carcinomas (HNSCC) represent a group of epithelial neoplasms that exhibit considerable heterogeneity in clinical behavior. Here, we examined the stromal and vascular heterogeneity in a panel of patient-derived xenograft (PDX) models of HNSCC and the impact on therapeutic response. Tumor sections from established tumors were stained for p16 (surrogate for human papillomavirus (HPV) infection), stromal (Masson's trichrome) and vascular (CD31) markers. All PDX models retained the HPV/p16 status of the original patient tumor. Immunohistochemical evaluation revealed the presence of multiple vessel phenotypes (tumor, stromal or mixed) in the PDX panel. Vascular phenotypes identified in the PDX models were validated in a tissue microarray of human HNSCC. Treatment with a microtubule targeted vascular disrupting agent (VDA) resulted in a heterogeneous antivascular and antitumor response in PDX models. The PDX with the tumor vessel phenotype that exhibited higher CD31+ vessel counts and leaky vasculature on magnetic resonance imaging (MRI) was sensitive to VDA treatment while the PDX with the stromal vessel phenotype was resistant to therapy. Collectively, our results demonstrate the phenotypic and functional vascular heterogeneity in HNSCC and highlight the impact of this heterogeneity on response to antivascular therapy in PDX models of HNSCC.


Evaluation of Lipid Accumulation Using Electrical Impedance Measurement under Three-Dimensional Culture Condition.

  • Daiki Zemmyo‎ et al.
  • Micromachines‎
  • 2019‎

The degeneration of adipocyte has been reported to cause obesity, metabolic syndrome, and other diseases. To treat these diseases, an effective in vitro evaluation and drug-screening system for adipocyte culture is required. The objective of this study is to establish an in vitro three-dimensional cell culture system to enable the monitoring of lipid accumulation by measuring electrical impedance, and to determine the relationship between the impedance and lipid accumulation of adipocytes cultured three dimensionally. Consequently, pre-adipocytes, 3T3-L1 cells, were cultured and differentiated to the adipocytes in our culture system, and the electrical impedance of the three-dimensional adipocyte culture at a high frequency was related to the lipid accumulation of the adipocytes. In conclusion, the lipid accumulation of adipocytes could be evaluated in real time by monitoring the electrical impedance during in vitro culture.


Environmental Foundations of Typhoid Fever in the Fijian Residential Setting.

  • Aaron P Jenkins‎ et al.
  • International journal of environmental research and public health‎
  • 2019‎

Proximal characteristics and conditions in the residential setting deserve greater attention for their potential to influence typhoid transmission. Using a case-control design in Central Division, Republic of Fiji, we examined bacterial (coliform and Escherichia coli) contamination and chemical composition of water and soil as potential vehicles of exposure to Salmonella Typhi, combining observational analysis of residential living conditions, geospatial analysis of household locations, and factor analysis to explore multivariate associations with the risk of developing typhoid fever. Factors positively associated with typhoid infection related to drainage [phosphate (OR 4.235, p = 0.042) and E. coli concentrations (OR 2.248, p = 0.029) in toilet drainage soil, housing [external condition (OR 3.712, p < 0.001)], drinking water contamination (OR 2.732, p = 0.003) and sanitary condition (OR 1.973, p = 0.031). These five factors explained 42.5% of the cumulative variance and were significant in predicting typhoid infection. Our results support the hypothesis that a combination of spatial and biophysical attributes of the residential setting influence the probability of typhoid transmission; in this study, factors associated with poor drainage, flooding, and sanitary condition increase local exposure to contaminated water and soil, and thereby infection. These findings extend testing of causal assumptions beyond the immediate domestic domain, enhance the scope of traditional case control epidemiology and allow greater specificity of interventions at the scale of the residential setting.


Overexpression of Acyl-ACP Thioesterases, CpFatB4 and CpFatB5, Induce Distinct Gene Expression Reprogramming in Developing Seeds of Brassica napus.

  • Jeong-Won Nam‎ et al.
  • International journal of molecular sciences‎
  • 2019‎

We examined the substrate preference of Cuphea paucipetala acyl-ACP thioesterases, CpFatB4 and CpFatB5, and gene expression changes associated with the modification of lipid composition in the seed, using Brassica napus transgenic plants overexpressing CpFatB4 or CpFatB5 under the control of a seed-specific promoter. CpFatB4 seeds contained a higher level of total saturated fatty acid (FA) content, with 4.3 times increase in 16:0 palmitic acid, whereas CpFatB5 seeds showed approximately 3% accumulation of 10:0 and 12:0 medium-chain FAs, and a small increase in other saturated FAs, resulting in higher levels of total saturated FAs. RNA-Seq analysis using entire developing pods at 8, 25, and 45 days after flowering (DAF) showed up-regulation of genes for β-ketoacyl-acyl carrier protein synthase I/II, stearoyl-ACP desaturase, oleate desaturase, and linoleate desaturase, which could increase unsaturated FAs and possibly compensate for the increase in 16:0 palmitic acid at 45 DAF in CpFatB4 transgenic plants. In CpFatB5 transgenic plants, many putative chloroplast- or mitochondria-encoded genes were identified as differentially expressed. Our results report comprehensive gene expression changes induced by alterations of seed FA composition and reveal potential targets for further genetic modifications.


Comparative in Vitro Cytotoxicity of Realistic Doses of Benchmark Multi-Walled Carbon Nanotubes towards Macrophages and Airway Epithelial Cells.

  • Luisana Di Cristo‎ et al.
  • Nanomaterials (Basel, Switzerland)‎
  • 2019‎

Multi-walled carbon nanotubes (MWCNT) have many outstanding physical and chemical properties that make them useful in many applications in nanotechnology. However, these properties are reported to be potentially harmful for the human body. The effects of low and realistic doses of three well-characterized preparations of MWCNT, obtained from the Joint Research Centre (JRC) (NM-400, NM-401, and NM-402), were assessed in two murine macrophage lines, Raw264.7, of peritoneal origin, and MH-S, derived from alveolar macrophages. Macrophage viability, evaluated with two distinct methods, was significantly lowered by NM-401 (needle-like, average length 4 μm, diameter 67 nm) with IC50 values of 10 μg/cm2, whereas NM-400 and NM-402 (tangled, average lengths 846-1372 nm, diameter 11 nm) had much smaller effects. In contrast, at 10 μg/cm2, NM-400 and NM-402 induced the M1 marker Nos2 and, consistently, a sizable accumulation of nitrites in the medium, whereas NM-401 had no significant effect. None of the MWCNT preparations induced the M2 marker Arg1. Phagocytic activity, assessed in Raw264.7 macrophages, was significantly reduced in cells exposed to NM-401, but not to NM-400 or NM-402. When tested on Calu-3 bronchial epithelial cell monolayers, the three MWCNT preparations did not affect cell viability, but decreased the trans-epithelial electrical resistance at the maximal dose tested (80 μg/cm2), with the most evident effect detected for NM-401, even at 10 μg/cm2. In conclusion, among the possible structural determinants of the toxic effects exerted by MWCNT towards macrophages and airway epithelial cells, shape and length appear the most relevant at low, realistic doses.


Congenital Sensorineural Hearing Loss and Inborn Pigmentary Disorders: First Report of Multilocus Syndrome in Piebaldism.

  • Laura Cristina Gironi‎ et al.
  • Medicina (Kaunas, Lithuania)‎
  • 2019‎

Congenital sensorineural hearing loss may occur in association with inborn pigmentary defects of the iris, hair, and skin. These conditions, named auditory-pigmentary disorders (APDs), represent extremely heterogeneous hereditary diseases, including Waardenburg syndromes, oculocutaneous albinism, Tietz syndrome, and piebaldism. APDs are part of the neurocristopathies, a group of congenital multisystem disorders caused by an altered development of the neural crest cells, multipotent progenitors of a wide variety of different lineages, including those differentiating into peripheral nervous system glial cells and melanocytes. We report on clinical and genetic findings of two monozygotic twins from a large Albanian family who showed a complex phenotype featured by sensorineural congenital deafness, severe neuropsychiatric impairment, and inborn pigmentary defects of hair and skin. The genetic analyzes identified, in both probands, an unreported co-occurrence of a new heterozygous germline pathogenic variant (c.2484 + 5G > T splicing mutation) in the KIT gene, consistent with the diagnosis of piebaldism, and a heterozygous deletion at chromosome 15q13.3, responsible for the neuropsychiatric impairment. This case represents the first worldwide report of dual locus inherited syndrome in piebald patients affected by a complex auditory-pigmentary multisystem phenotype. Here we also synthesize the clinical and genetic findings of all known neurocristopathies characterized by a hypopigmentary congenital disorder.


PEA-15 C-Terminal Tail Allosterically Modulates Death-Effector Domain Conformation and Facilitates Protein-Protein Interactions.

  • Sergio L Crespo-Flores‎ et al.
  • International journal of molecular sciences‎
  • 2019‎

Phosphoprotein enriched in astrocytes, 15 kDa (PEA-15) exerts its regulatory roles on several critical cellular pathways through protein-protein interactions depending on its phosphorylation states. It can either inhibit the extracellular signal-regulated kinase (ERK) activities when it is dephosphorylated or block the assembly of death-inducing signaling complex (DISC) and the subsequent activation of apoptotic initiator, caspase-8, when it is phosphorylated. Due to the important roles of PEA-15 in regulating these pathways that lead to opposite cellular outcomes (cell proliferation vs. cell death), we proposed a phosphostasis (phosphorylation homeostasis) model, in which the phosphorylation states of the protein are vigorously controlled and regulated to maintain a delicate balance. The phosphostasis gives rise to the protective cellular functions of PEA-15 to preserve optimum cellular conditions. In this article, using advanced multidimensional nuclear magnetic resonance (NMR) techniques combined with a novel chemical shift (CS)-Rosetta algorithm for de novo protein structural determination, we report a novel conformation of PEA-15 death-effector domain (DED) upon interacting with ERK2. This new conformation is modulated by the irregularly structured C-terminal tail when it first recognizes and binds to ERK2 at the d-peptide recruitment site (DRS) in an allosteric manner, and is facilitated by the rearrangement of the surface electrostatic and hydrogen-bonding interactions on the DED. In this ERK2-bound conformation, three of the six helices (α2, α3, and α4) comprising the DED reorient substantially in comparison to the free-form structure, exposing key residues on the other three helices that directly interact with ERK2 at the DEF-docking site (docking site for ERK, FxF) and the activation loop. Additionally, we provide evidence that the phosphorylation of the C-terminal tail leads to a distinct conformation of DED, allowing efficient interactions with Fas-associated death domain (FADD) protein at the DISC. Our results substantiate the allosteric regulatory roles of the C-terminal tail in modulating DED conformation and facilitating protein-protein interactions of PEA-15.


Structure-Antioxidant-Antiproliferative Activity Relationships of Natural C7 and C7-C8 Hydroxylated Flavones and Flavanones.

  • Sandra Sordon‎ et al.
  • Antioxidants (Basel, Switzerland)‎
  • 2019‎

Common food flavonoids: chrysin, apigenin, luteolin, diosmetin, pinocembrin, naringenin, eriodictyol, hesperetin, and their analogues with an additional hydroxyl group at the C-8 position obtained via biotransformation were tested for antioxidant activity using the ABTS, DPPH, and ferric ion reducing antioxidant power (FRAP) methods. They were also tested for antiproliferative activity against selected human cancer cell lines-MV-4-11 (biphenotypic B myelomonocytic leukemia), MCF7 (breast carcinoma), LoVo (colon cancer), LoVo/DX (colon cancer doxorubicin resistant), and DU 145 (prostate cancer)-and two normal human cell lines-MCF 10A (breast cells) and HLMEC (lung microvascular endothelial cells). Flavonoids with a C7-C8 catechol moiety indicated much higher antioxidant activity compared with the C7 hydroxy analogues. However, because they were unstable under the assay conditions, they did not show antiproliferative activity or it was very low.


Application of Near-infrared Spectroscopy and Multiple Spectral Algorithms to Explore the Effect of Soil Particle Sizes on Soil Nitrogen Detection.

  • Shupei Xiao‎ et al.
  • Molecules (Basel, Switzerland)‎
  • 2019‎

Soil nitrogen is the key parameter supporting plant growth and development; it is also the material basis of plant growth. An accurate grasp of soil nitrogen information is the premise of scientific fertilization in precision agriculture, where near-infrared (NIR) spectroscopy is widely used for rapid detection of soil nutrients. In this study, the variation law of soil NIR reflectivity spectra with soil particle sizes was studied. Moreover, in order to precisely study the effect of particle size on soil nitrogen detection by NIR, four different spectra preprocessing methods and five different chemometric modeling methods were used to analyze the soil NIR spectra. The results showed that the smaller the soil particle sizes, the stronger the soil NIR reflectivity spectra. Besides, when the soil particle sizes ranged 0.18-0.28 mm, the soil nitrogen prediction accuracy was the best based on the partial least squares (PLS) model with the highest Rp2 of 0.983, the residual predictive deviation (RPD) of 6.706. The detection accuracy was not ideal when the soil particle sizes were too big (1-2 mm) or too small (0-0.18 mm). In addition, the relationship between the mixing spectra of six different soil particle sizes and the soil nitrogen detection accuracy was studied. It was indicated that the larger the gap between soil particle sizes, the worse the accuracy of soil nitrogen detection. In conclusion, soil nitrogen detection precision was affected by soil particle sizes to a large extent. It is of great significance to optimize the pre-treatments of soil samples to realize rapid and accurate detection by NIR spectroscopy.


Application of Butylamine as a Conjugative Reagent to On-Column Derivatization for the Determination of Antioxidant Amino Acids in Brain Tissue, Plasma, and Urine Samples.

  • Kamila Borowczyk‎ et al.
  • International journal of molecular sciences‎
  • 2019‎

(1) Antioxidants are involved in body protection mechanisms against reactive oxygen species. Amino acids such as glutathione (GSH) and N-acetylcysteine (NAC) are known to be involved in providing protection against oxidative lethality. A quick and simple method for the determination of NAC and GSH in various biological matrices such as urine, plasma, and homogenates of brain tissues has been developed and described in this work. (2) The assay is based on reversed phase high performance liquid chromatography with spectrofluorimetric detection and on-column derivatization. Butylamine and o-phthaldialdehyde have been used as derivatization reagents. Since o-phthaldialdehyde constitutes a part of the mobile phase, the derivatization reaction and chromatographic separation occur simultaneously. (3) Linearity in the detector response for NAC in human urine was observed in the range of 5-200 nmol mL-1, and NAC and GSH in the brain tissue homogenates were observed in the range of 0.5-5 nmol mL-1 and 0.5-15 nmol mL-1, respectively. Human plasma linearity ranges covered 0.25-5.00 nmol mL-1 and 0.5-15 nmol mL-1 for NAC and GSH, respectively. The LODs for NAC and GSH were 0.01 and 0.02 nmol mL-1 while the LOQs were 0.02 and 0.05 nmol mL-1, respectively. The usefulness of the proposed method was proven through its application to real samples.


Protective effect of phosphatidylserine blockade in sepsis induced organ dysfunction.

  • Genna Beattie‎ et al.
  • Surgery‎
  • 2019‎

Phosphatidylserine is usually an intracellularly oriented cell membrane phospholipid. Externalized phosphatidylserine on activated cells is a signal for phagocytosis. In sepsis, persistent phosphatidylserine exposure is also a signal for activation of the coagulation and inflammatory cascades. As such, phosphatidylserine may be a key molecule in sepsis induced cellular and organ injury. We hypothesize that phosphatidylserine blockade provides a protective effect in sepsis induced organ dysfunction.


18F-labeled benzimidazopyridine derivatives for PET imaging of tau pathology in Alzheimer's disease.

  • Sho Kaide‎ et al.
  • Bioorganic & medicinal chemistry‎
  • 2019‎

Hyperphosphorylated tau proteins are one of the neuropathological hallmarks in the Alzheimer's disease (AD) brain. The in vivo imaging of tau aggregates with nuclear medical imaging probes is helpful for the further comprehension of and medical intervention in the AD pathology. For tau-selective PET imaging, we newly designed and synthesized 18F-labeled benzimidazopyridine (BIP) derivatives with fluoroalkylamino groups, [18F]IBIPF1 and [18F]IBIPF2, and evaluated their utilities as tau imaging probes. They both bound selectively to tau against amyloid β (Aβ) aggregates in AD brain sections in vitro, and showed good pharmacokinetics in mouse brains in vivo. Notably, [18F]IBIPF1 exhibited high tau-selectivity (Tau/Aβ ratio = 34.8), high brain uptake (6.22% ID/g at 2 min postinjection), and subsequent washout (2.77% ID/g at 30 min postinjection). In vivo analysis of radiometabolites indicated that [18F]IBIPF1 was stable against metabolism in the mouse brain. These encouraging preclinical results suggest that further structural optimization based on the BIP scaffold may lead to the development of more useful tau imaging probes.


Phosphatidylserine decarboxylase is critical for the maintenance of skeletal muscle mitochondrial integrity and muscle mass.

  • Ahrathy Selathurai‎ et al.
  • Molecular metabolism‎
  • 2019‎

Phosphatidylethanolamine (PtdEtn) is a major phospholipid in mammals. It is synthesized via two pathways, the CDP-ethanolamine pathway in the endoplasmic reticulum and the phosphatidylserine (PtdSer) decarboxylase (PSD) pathway in the mitochondria. While the CDP-ethanolamine pathway is considered the major route for PtdEtn synthesis in most mammalian tissues, little is known about the importance of the PSD pathway in vivo, especially in tissues enriched with mitochondria such as skeletal muscle. Therefore, we aimed to examine the role of the mitochondrial PSD pathway in regulating PtdEtn homeostasis in skeletal muscle in vivo.


Microbial Succession of Anaerobic Chitin Degradation in Freshwater Sediments.

  • Susanne Wörner‎ et al.
  • Applied and environmental microbiology‎
  • 2019‎

Chitin is massively produced by freshwater plankton species as a structural element of their exoskeleton or cell wall. At the same time, chitin does not accumulate in the predominantly anoxic sediments, underlining its importance as carbon and nitrogen sources for sedimentary microorganisms. We studied chitin degradation in littoral sediment of Lake Constance, Central Europe's third largest lake. Turnover of the chitin analog methyl-umbelliferyl-N,N-diacetylchitobioside (MUF-DC) was highest in the upper oxic sediment layer, with 5.4 nmol MUF-DC h-1 (g sediment [dry weight])-1 In the underlying anoxic sediment layers, chitin hydrolysis decreased with depth from 1.1 to 0.08 nmol MUF-DC h-1 (g sediment [dry weight])-1 Bacteria involved in chitin degradation were identified by 16S rRNA (gene) amplicon sequencing of anoxic microcosms incubated in the presence of chitin compared to microcosms amended either with N-acetylglucosamine as the monomer of chitin or no substrate. Chitin degradation was driven by a succession of bacteria responding specifically to chitin only. The early phase (0 to 9 days) was dominated by Chitinivibrio spp. (Fibrobacteres). The intermediate phase (9 to 21 days) was characterized by a higher diversity of chitin responders, including, besides Chitinivibrio spp., also members of the phyla Bacteroidetes, Proteobacteria, Spirochaetes, and Chloroflexi In the late phase (21 to 43 days), the Chitinivibrio populations broke down with a parallel strong increase of Ruminiclostridium spp. (formerly Clostridium cluster III, Firmicutes), which became the dominating chitin responders. Our study provides quantitative insights into anaerobic chitin degradation in lake sediments and linked this to a model of microbial succession associated with this activity.IMPORTANCE Chitin is the most abundant biopolymer in aquatic environments, with a direct impact on the carbon and nitrogen cycles. Despite its massive production as a structural element of crustaceans, insects, or algae, it does not accumulate in sediments. Little is known about its turnover in predominantly anoxic freshwater sediments and the responsible microorganisms. We proved that chitin is readily degraded under anoxic conditions and linked this to a succession of the members of the responsible microbial community over a 43-day period. While Fibrobacteres and Firmicutes members were driving the early and late phases of chitin degradation, respectively, a more diverse community was involved in chitin degradation in the intermediate phase. Entirely different microorganisms responded toward the chitin monomer N-acetylglucosamine, which underscores that soluble monomers are poor and misleading substrates to study polymer-utilizing microorganisms. Our study provides quantitative insights into the microbial ecology driving anaerobic chitin degradation in freshwater sediments.


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