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Yiqun Mo, Yue Zhang, Qunwei Zhang
Nanoparticles can enter the body via the lungs, the digestive tract, and the skin. The pulmonary effects of nanoparticles and the underlying mechanisms may be investigated by histopathological examination, immunostaining, bronchoalveolar lavage (BAL), and so on. BAL is a simple, fast, and inexpensive method that is commonly used to investigate the immune cells and acellular components in the lungs, which reflect the health state of the lungs. In this chapter, we describe the detailed procedures of performing BAL on mouse lungs...
2019: Methods in Molecular Biology
Zhaobin Kuang, Yujia Bao, James Thomson, Michael Caldwell, Peggy Peissig, Ron Stewart, Rebecca Willett, David Page
We present the baseline regularization model for computational drug repurposing using electronic health records (EHRs). In EHRs, drug prescriptions of various drugs are recorded throughout time for various patients. In the same time, numeric physical measurements (e.g., fasting blood glucose level) are also recorded. Baseline regularization uses statistical relationships between the occurrences of prescriptions of some particular drugs and the increase or the decrease in the values of some particular numeric physical measurements to identify potential repurposing opportunities...
2019: Methods in Molecular Biology
Javad Heshmati, Farnaz Farsi, Somaye Yosaee, Maryam Razavi, Mahroo Rezaeinejad, Elham Karimie, Mahdi Sepidarkish
We searched bibliographic databases from inception through May 2018 to evaluate the effect of probiotics (or synbiotics) supplementation in women suffering from polycystic ovary syndrome (PCOS). Seven trials involving 236 women with PCOS and 235 controls were included in the meta-analysis. Comparing with the control group, probiotics (or synbiotics) may improve Quantitative insulin sensitivity check index (QUICKI) (standardized mean difference (SMD) 0.41, 95% confidence intervals (CI) 0.01 to 0.82, P = 0...
December 13, 2018: Probiotics and Antimicrobial Proteins
Keith Bowering, Helena W Rodbard, David Russell-Jones, Bruce Bode, Stewart Harris, Milivoj Piletic, Simon Heller, Vincent Woo, Vinay Babu, Claus Dethlefsen, Chantal Mathieu
INTRODUCTION: The aim of this study was to investigate the association between baseline characteristics [HbA1c and body mass index (BMI)] and the effect of mealtime fast-acting insulin aspart (faster aspart) relative to insulin aspart (IAsp) or basal-only insulin therapy on several efficacy and safety outcomes in people with diabetes. METHODS: Post hoc analysis of three randomised phase 3a trials in people with type 1 diabetes (T1D; onset 1) and type 2 diabetes (T2D; onset 2 and 3)...
December 13, 2018: Diabetes Therapy: Research, Treatment and Education of Diabetes and related Disorders
Vincent Pautu, Adélie Mellinger, Pauline Resnier, Elise Lepeltier, Ludovic Martin, Lise Boussemart, Franck Letournel, Catherine Passirani, Nicolas Clere
Tumour angiogenesis is defined by an anarchic vasculature and irregularities in alignment of endothelial cells. These structural abnormalities could explain the variability in distribution of nanomedicines in various tumour models. Then, the main goal of this study was to compare and to characterize the tumour vascular structure in different mouse models of melanoma tumours (B16F10 and SK-Mel-28) and in human melanomas from different patients. Tumours were obtained by subcutaneous injection of 106 B16F10 and 3...
December 13, 2018: Journal of Cancer Research and Clinical Oncology
Tomasz Górski, Romain Veltz, Mathieu Galtier, Hélissande Fragnaud, Jennifer S Goldman, Bartosz Teleńczuk, Alain Destexhe
Many neurons possess dendrites enriched with sodium channels and are capable of generating action potentials. However, the role of dendritic sodium spikes remain unclear. Here, we study computational models of neurons to investigate the functional effects of dendritic spikes. In agreement with previous studies, we found that point neurons or neurons with passive dendrites increase their somatic firing rate in response to the correlation of synaptic bombardment for a wide range of input conditions, i.e. input firing rates, synaptic conductances, or refractory periods...
December 13, 2018: Journal of Computational Neuroscience
Michèlle van der Does, Peter Knippertz, Philipp Zschenderlein, R Giles Harrison, Jan-Berend W Stuut
Giant mineral dust particles (>75 μm in diameter) found far from their source have long puzzled scientists. These wind-blown particles affect the atmosphere's radiation balance, clouds, and the ocean carbon cycle but are generally ignored in models. Here, we report new observations of individual giant Saharan dust particles of up to 450 μm in diameter sampled in air over the Atlantic Ocean at 2400 and 3500 km from the west African coast. Past research points to fast horizontal transport, turbulence, uplift in convective systems, and electrical levitation of particles as possible explanations for this fascinating phenomenon...
December 2018: Science Advances
Hiroshi Akima, Keigo Kainuma, Kenji Togashi
Objective . This study investigated relationships between adipose tissue deposition within skeletal muscle and morphological and biochemical variables in children with obesity. Methods . Fifty-one Japanese children (16 girls) aged 7 to 16 years were assigned to either mild (<20%), moderate (≥20% to <50%), or severe obesity groups (≥50%). Computed tomography images were taken to calculate the cross-sectional area (CSA) of muscle, subcutaneous and visceral adipose tissue (VAT, for abdomen only), and muscle signal intensities, as an index of intramuscular adipose tissue in the anterior, lateral, and posterior muscles of the abdomen and quadriceps, hamstring and adductor muscles in the thigh...
2018: Global Pediatric Health
Ӧzlem Türeci, Rita Mitnacht-Kraus, Stefan Wöll, Tomohiro Yamada, Ugur Sahin
In healthy tissue, the tight junction protein Claudin 18.2 (CLDN18.2) is present only in the gastric mucosa. Upon malignant transformation of gastric epithelial tissue, perturbations in cell polarity lead to cell surface exposure of CLDN18.2 epitopes. Moreover, CLDN18.2 is aberrantly expressed in malignancies of several other organs, such as pancreatic cancer (PC). A monoclonal antibody, zolbetuximab (formerly known as IMAB362), has been generated against CLDN18.2. In a phase 2 clinical trial (FAST: NCT01630083), zolbetuximab in conjunction with chemotherapy prolonged overall and progression-free survival over chemotherapy alone and improved quality of life...
2019: Oncoimmunology
Francesca Castoldi, Erika Vacchelli, Laurence Zitvogel, Maria Chiara Maiuri, Federico Pietrocola, Guido Kroemer
The success of chemotherapy largely depends on the anticancer immune response triggered by tumor cells that succumb to immunogenic cell death (ICD). One of the hallmarks of ICD is premortem autophagy that facilitates the release of adenosine triphosphate from dying cancer cells and acts as a chemoattractant for dendritic cell precursors. Here, we show that the immune response induced by inoculation of cancer cells undergoing ICD in response to the anthracycline mitoxantrone (MTX) can be improved by a short-term fasting regimen (48 hours of starvation) and that this effect is reversed by systemic administration of the autophagy inhibitor dimethyl α-ketoglutarate...
2019: Oncoimmunology
Mohammad J Alkhatatbeh, Khalid K Abdul-Razzak
In the present study, the aim was to investigate the association between serum 25-hydroxyvitamin D concentration and measures of glycemic control including hemoglobin A1c (HbA1c) and fasting blood glucose (FBG) in adult patients with diabetes mellitus (DM) from the north of Jordan. Another aim was to compare serum levels of 25-hydroxyvitamin D between patients with good glycemic control and patients with uncontrolled DM. This was a cross-sectional study that included 261 participants with DM. The concentration of 25-hydroxyvitamin D was measured using electrochemiluminescence immunoassay, HbA1c was measured using turbidimetric inhibition immunoassay and FBG was measured using the hexokinase method...
December 2018: Biomedical Reports
Noémi M Nagy, József Kónya
The sorption of phosphate on soils is studied by radioisotopic tracer method. Two consecutive processes with rather different rates were differentiated: namely the heterogeneous isotope exchange between the phosphate in the soil solution and the weakly sorbed phosphate (fast reaction), and the transformation of weakly sorbed phosphate to tightly sorbed phosphate (slow reaction). In this paper, it is shown how the rate constants of these two processes can be determined by a radiotracer with a relatively short half-life...
2018: Journal of Radioanalytical and Nuclear Chemistry
Zsolt Varga, Adrian Nicholl, Erich Hrnecek, Maria Wallenius, Klaus Mayer
The paper describes the age (production date) determination of uranium reference materials using the 231 Pa/235 U ratio. Direct addition of 237 Np in secular equilibrium with its 233 Pa daughter was chosen instead of the regular milking of 237 Np to avoid possible loss of Pa. Sample preparation consists of a fast, one-step procedure. The developed method using ICP-MS for the measurement of 231 Pa is more precise than alpha spectrometry and is applicable for freshly produced low-enriched uranium materials. The measured ages are in good agreement with the reported production dates, thus the 231 Pa/235 U chronometer can be applied for validation of 230 Th/234 U in nuclear forensics and safeguards...
2018: Journal of Radioanalytical and Nuclear Chemistry
Hung-Ling Huang, Meng-Hsuan Cheng, Po-Liang Lu, Chia-Jung Liu, Inn-Wen Chong, Jann-Yuan Wang
The clinical significance of a single Mycobacterium kansasii (MK) isolation in multiple sputum samples remains unknown. We conducted this study to evaluate the outcome and predictors of developing MK-pulmonary disease (PD) within 1 year among these patients. Patients with a single MK isolation from ≥3 sputum samples collected within 3 months and ≥2 follow-up sputum samples and chest radiography in the subsequent 9 months between 2008 and 2016 were included. The primary outcome was development of MK-PD within 1 year, with its predictors explored using multivariate logistic regression analysis...
December 13, 2018: Scientific Reports
Elizabeth R De Leon, Jacqueline A Brinkman, Rachel J Fenske, Trillian Gregg, Brian A Schmidt, Dawn S Sherman, Nicole E Cummings, Darby C Peter, Michelle E Kimple, Dudley W Lamming, Matthew J Merrins
Type 2 diabetes is an age-and-obesity associated disease driven by impairments in glucose homeostasis that ultimately result in defective insulin secretion from pancreatic β-cells. To deconvolve the effects of age and obesity in an experimental model of prediabetes, we fed young and aged mice either chow or a short-term high-fat/high-sucrose Western diet (WD) and examined how weight, glucose tolerance, and β-cell function were affected. Although WD induced a similar degree of weight gain in young and aged mice, a high degree of heterogeneity was found exclusively in aged mice...
December 13, 2018: Scientific Reports
Anna Tvorogova, Aleena Saidova, Tatiana Smirnova, Ivan Vorobjev
When cells with a mesenchymal type of motility come into contact with an adhesive substrate they adhere and start spreading by the formation of lamellipodia. Using a label-free approach and virtual synchronization approach we analyzed spreading in fibroblasts and cancer cells. In all cell lines spreading is a non-linear process undergoing isotropic or anisotropic modes with first fast (5-20 min) and then slow (30-120 min) phases. In the first 10 min cell area increases 2-4 times, while the absolute rate of initial spreading decreases 2-8 times...
December 13, 2018: Biology Open
Boya Wang, Chris Thachuk, Andrew D Ellington, Erik Winfree, David Soloveichik
Artificially designed molecular systems with programmable behaviors have become a valuable tool in chemistry, biology, material science, and medicine. Although information processing in biological regulatory pathways is remarkably robust to error, it remains a challenge to design molecular systems that are similarly robust. With functionality determined entirely by secondary structure of DNA, strand displacement has emerged as a uniquely versatile building block for cell-free biochemical networks. Here, we experimentally investigate a design principle to reduce undesired triggering in the absence of input (leak), a side reaction that critically reduces sensitivity and disrupts the behavior of strand displacement cascades...
December 13, 2018: Proceedings of the National Academy of Sciences of the United States of America
Daofu Yuan, Yafu Guan, Wentao Chen, Hailin Zhao, Shengrui Yu, Chang Luo, Yuxin Tan, Ting Xie, Xingan Wang, Zhigang Sun, Dong H Zhang, Xueming Yang
Theory has established the importance of geometric phase (GP) effects in the adiabatic dynamics of molecular systems with a conical intersection connecting the ground- and excited-state potential energy surfaces, but direct observation of their manifestation in chemical reactions remains a major challenge. Here, we report a high-resolution crossed molecular beams study of the H + HD → H2 + D reaction at a collision energy slightly above the conical intersection. Velocity map ion imaging revealed fast angular oscillations in product quantum state-resolved differential cross sections in the forward scattering direction for H2 products at specific rovibrational levels...
December 14, 2018: Science
Yohsuke Ohkubo, Takashi Sekido, Shin-Ichi Nishio, Keiko Sekido, Junichiro Kitahara, Satoru Suzuki, Mitsuhisa Komatsu
The thyroid hormone-binding protein μ-crystallin (CRYM) mediates thyroid hormone action by sequestering triiodothyronine in the cytoplasm and regulating the intracellular concentration of thyroid hormone. As thyroid hormone action is closely associated with glycolipid metabolism, it has been proposed that CRYM may contribute to this process by reserving or releasing triiodothyronine in the cytoplasm. We aimed to clarify the relationship between CRYM and glycolipid metabolism by comparing wild-type and CRYM knockout mice fed a high-fat diet...
December 10, 2018: Biochemical and Biophysical Research Communications
Alexander M Matyushenko, Daniil V Shchepkin, Denis S Susorov, Victoria V Nefedova, Galina V Kopylova, Valentina Y Berg, Sergey Y Kleymenov, Dmitrii I Levitsky
Tropomyosin (Tpm) is an α-helical coiled-coil actin-binding protein that plays a key role in the Ca2+ -regulated contraction of striated muscles. Two Tpm isoforms, α (Tpm 1.1) and β (Tpm 2.2), are expressed in fast skeletal muscles. These Tpm isoforms can form either αα and ββ homodimers, or αβ heterodimers. However, only αα-Tpm and αβ-Tpm dimers are usually present in most of fast skeletal muscles, because ββ-homodimers are relatively unstable and cannot exist under physiologic conditions. Nevertheless, the most of previous studies of myopathy-causing mutations in the Tpm β-chains were performed on the ββ-homodimers...
December 10, 2018: Biochemical and Biophysical Research Communications
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