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Ines Marek, Robert Becker, Fabian B Fahlbusch, Carlos Menendez-Castro, Wolfgang Rascher, Christoph Daniel, Gudrun Volkert, Andrea Hartner
BACKGROUND/AIMS: Healing of mesangioproliferative glomerulonephritis involves degradation of excess extracellular matrix, resolution of hypercellularity by apoptosis and phagocytosis of apoptotic cells. Integrin receptors participate in the regulation of phagocytosis. In mice deficient for alpha8 integrin (Itga8-/-) healing of glomerulonephritis is delayed. As Itga8 is abundant in mesangial cells (MC) which are non-professional phagocytes, we hypothesized that Itga8 facilitates phagocytosis of apoptotic cells and matrix components by MC...
March 10, 2018: Cellular Physiology and Biochemistry
Huihui Sun, Naijun Wan, Xinli Wang, Liang Chang, Dazhi Cheng
18p deletion syndrome is a rare chromosomal disease caused by deletion of the short arm of chromosome 18. By using cytogenetic and SNP array analysis, we identified a girl with 18p deletion syndrome exhibiting craniofacial anomalies, intellectual disability, and short stature. G-banding analysis of metaphase cells revealed an abnormal karyotype 46,XX,del(18)(p10). Further, SNP array detected a 15.3-Mb deletion at 18p11.21p11.32 (chr18:12842-15375878) including 61 OMIM genes. Genotype-phenotype correlation analysis showed that clinical manifestations of the patient were correlated with LAMA1, TWSG1, and GNAL deletions...
March 16, 2018: Cytogenetic and Genome Research
Ceren D Durmaz, Gareth Evans, Miriam J Smith, Pelin Ertop, Bengü N Akay, Timur Tuncalı
Nevoid basal cell carcinoma syndrome (NBCCS), also known as Gorlin syndrome, is a rare multisystemic autosomal dominant disorder typically presenting with cutaneous basal cell carcinomas, multiple keratocysts, and skeletal anomalies. NBCCS is caused by heterozygous mutations in the PTCH1 gene in chromosome 9q22, in the PTCH2 gene in 1p34, or the SUFU gene in 10q24.32. Here, we report on an 18-month-old boy presenting with medulloblastoma, frontal bossing, and multiple skeletal anomalies and his father who has basal cell carcinomas, palmar pits, macrocephaly, bifid ribs, calcification of falx cerebri, and a history of surgery for odontogenic keratocyst...
March 16, 2018: Cytogenetic and Genome Research
Jinyu Wang, Haitao Zhang, Mohammed Al Shibar, Belinda Willard, Alo Ray, Kurt W Runge
Telomeres, the ends of eukaryotic chromosomes, consist of repetitive DNA sequences and their bound proteins that protect the end from the DNA damage response. Short telomeres with fewer repeats are preferentially elongated by telomerase. Tel1, the yeast homolog of human ATM kinase, is preferentially recruited to short telomeres and Tel1 kinase activity is required for telomere elongation. Rif1, a telomere-binding protein, negatively regulates telomere length by forming a complex with two other telomere binding proteins, Rap1 and Rif2, to block telomerase recruitment...
March 7, 2018: DNA Repair
Oriane Blanquie, Frank Bradke
Recent years have seen cytoskeleton dynamics emerging as a key player in axon regeneration. The cytoskeleton, in particular microtubules and actin, ensures the growth of neuronal processes and maintains the singular, highly polarized shape of neurons. Following injury, adult central axons are tipped by a dystrophic structure, the retraction bulb, which prevents their regeneration. Abnormal cytoskeleton dynamics are responsible for the formation of this growth-incompetent structure but pharmacologically modulating cytoskeleton dynamics of injured axons can transform this structure into a growth-competent growth cone...
March 12, 2018: Current Opinion in Neurobiology
Naif O Al-Harbi, Ahmed Nadeem, Sheikh F Ahmad, Moureq R Alotaibi, Abdullah F AlAsmari, Wael A Alanazi, Mohammad M Al-Harbi, Ahmad M El-Sherbeeny, Khalid E Ibrahim
Sepsis affects millions of people worldwide and is associated with acute kidney injury (AKI). Innate and adaptive immune cells have been shown to play an important role in AKI through release of various inflammatory mediators which include reactive oxidant species (ROS). Acetate, a short chain fatty acid produced by gut bacteria has anti-inflammatory properties and has also been shown to modulate oxidative stress in different immune cells. Effects of acetate have been shown to be both GPR43 dependent and independent in different cells/tissues...
March 12, 2018: International Immunopharmacology
Alzbeta Bujnakova Mlynarcikova, Sona Scsukova
In the present study, we aimed to examine effects of different concentrations of the endocrine disruptor Bisphenol A (BPA; 1 nM, 1 μM, 100 μM) and the flavonoid fisetin (1, 10, 25, 50 μM), individually and in combinations, on steroidogenic function of porcine ovarian granulosa cells (GCs) represented by progesterone production. We confirmed that BPA inhibited progesterone production by GCs at the highest concentration. Fisetin reduced gonadotropin-stimulated progesterone synthesis dose-dependently, and in this manner, fisetin impaired progesterone production when added to BPA-treated GCs...
March 2, 2018: Environmental Toxicology and Pharmacology
Mizuki Ikeda, Junji Deguchi, Shota Fukushima, Ai Qingyu, Norihiro Katayama, Hajime Miura, Yasuo Oyama
Chlorothalonil, a polychlorinated aromatic fungicide, is considered non-toxic to small mammals. However, chlorothalonil inactivates sulfhydryl enzymes and depletes cellular glutathione. Chlorothalonil increases intracellular Zn2+ concentration ([Zn2+ ]i) in mammalian cells possibly because intracellular Zn2+ is released via zinc-thiol/disulfide interchange. The effects of chlorothalonil at sublethal concentrations on the cellular content of nonprotein thiols ([NPT]i) and [Zn2+ ]i were examined using flow cytometry in rat thymocytes...
March 8, 2018: Environmental Toxicology and Pharmacology
Yuichi Goto, Yoshihiro Uchino, Shin Sasaki, Nobuhisa Shirahama, Yoriko Nomura, Jun Akiba, Hiroto Ishikawa, Yoshito Akagi, Hiroyuki Tanaka, Koji Okuda
INTRODUCTION: We report a rare case of complete spontaneous necrosis of a hepatocellular carcinoma (HCC) accompanied by portal vein tumor thrombosis (PVTT), as confirmed by resection. CASE PRESENTATION: A 64-year-old man was referred to our hospital for suspected HCC. Contrast-enhanced computed tomography (CECT) findings before admission revealed a 53-mm tumor in the posterior segment of the liver and were suspicious for PVTT in the right posterior PV. Both alpha-fetoprotein (AFP) and proteins induced by vitamin K absence or antagonist-II (PIVKA-II) were elevated at 17,562 ng/mL and 153 mAU/mL, respectively...
March 7, 2018: International Journal of Surgery Case Reports
Ekaterina M Savelieva, Vladimir E Oslovsky, Dmitry S Karlov, Nikolay N Kurochkin, Irina A Getman, Sergey N Lomin, Georgy V Sidorov, Sergey N Mikhailov, Dmitry I Osolodkin, Georgy A Romanov
Biological effects of hormones in both plants and animals are based on high-affinity interaction with cognate receptors resulting in their activation. The signal of cytokinins, classical plant hormones, is perceived in Arabidopsis by three homologous membrane receptors: AHK2, AHK3, and CRE1/AHK4. To study the cytokinin-receptor interaction, we used 25 derivatives of potent cytokinin N6 -benzyladenine (BA) with substituents in the purine heterocycle and/or in the side chain. The study was focused primarily on individual cytokinin receptors from Arabidopsis...
March 12, 2018: Phytochemistry
Mathias Reisbeck, Lukas Richter, Michael Johannes Helou, Stephan Arlinghaus, Birgit Anton, Ignas van Dommelen, Mario Nitzsche, Michael Baßler, Barbara Kappes, Oliver Friedrich, Oliver Hayden
Time-of-flight (TOF) magnetic sensing of rolling immunomagnetically-labeled cells offers great potential for single cell function analysis at the bedside in even optically opaque media, such as whole blood. However, due to the spatial resolution of the sensor and the low flow rate regime required to observe the behavior of rolling cells, the concentration range of such a workflow is limited. Potential clinical applications, such as testing of leukocyte function, require a cytometer which can cover a cell concentration range of several orders of magnitude...
March 12, 2018: Biosensors & Bioelectronics
Godwin U Ebiloma, Teresa Díaz Ayuga, Emmanuel O Balogun, Lucía Abad Gil, Anne Donachie, Marcel Kaiser, Tomás Herraiz, Daniel K Inaoka, Tomoo Shiba, Shigeharu Harada, Kiyoshi Kita, Harry P de Koning, Christophe Dardonville
African trypanosomiasis is a neglected parasitic disease that is still of great public health relevance, and a severe impediment to agriculture in endemic areas. The pathogens possess certain unique metabolic features that can be exploited for the development of new drugs. Notably, they rely on an essential, mitochondrially-localized enzyme, Trypanosome Alternative Oxidase (TAO) for their energy metabolism, which is absent in the mammalian hosts and therefore an attractive target for the design of safe drugs...
February 26, 2018: European Journal of Medicinal Chemistry
Qiang Wang, Feiyang Liu, Shuang Qi, Ziping Qi, Xiao-E Yan, Beilei Wang, Aoli Wang, Wei Wang, Cheng Chen, Xiaochuan Liu, Zongru Jiang, Zhenquan Hu, Li Wang, Wenchao Wang, Tao Ren, Shanchun Zhang, Cai-Hong Yun, Qingsong Liu, Jing Liu
Through exploration of the non-highly conserved allosteric hydrophobic pocket generated by DFG-out shifting in the inactive conformation, we discovered a highly selective type II PDGFRα kinase inhibitor 15i (CHMFL-PDGFRα-159), which exhibited strong potency against purified PDGFRα (IC50 : 132 nM) but not structurally similar PDGFRβ, ABL, c-KIT and VEGFR2 kinases. In addition, it displayed a high selectivity profile (S score (10) = 0.02) at the concentration of 1 μM among 468 kinases/mutants in the KINOMEscan profiling...
March 12, 2018: European Journal of Medicinal Chemistry
Eun-Ji Choi, Je-Hwan Lee, Jung-Hee Lee, Han-Seung Park, Sun-Hye Ko, Eun-Hye Hur, Juhyun Moon, Bon-Kwan Goo, Yeonhee Kim, Miee Seol, Young-Shin Lee, Young-Ah Kang, Mijin Jeon, Ji Min Woo, Kyoo-Hyung Lee
This retrospective analysis compared anthracyclines (as part of an induction regimen) in 128 newly diagnosed FLT3-ITD-mutated AML patients. Induction regimens comprised high-dose daunorubicin (HD-DN; 90 mg/m2 /d × 3d; n = 44), standard-dose daunorubicin (SD-DN; 45 mg/m2 /d × 3d; n = 51), or idarubicin (IDA; 12 mg/m2 /d × 3d; n = 33) in combination with cytarabine (100-200 mg/m2 /d × 7d). Fifty-three patients showing persistent leukemia on interim bone marrow examination received a second course of induction chemotherapy comprising 2 days of daunorubicin (45 mg/m2 /d) or IDA (8 or 12 mg/m2 /d) in addition to 5 days of cytarabine...
March 8, 2018: Leukemia Research
Irena Branyikova, Monika Filipenska, Katerina Urbanova, Marek C Ruzicka, Martin Pivokonsky, Tomas Branyik
Alkaline flocculation has been studied due to its potential as a low-cost harvesting method for microalgae. However, surface properties (zeta potential, contact angles) as inputs into physicochemical interaction models have not yet been applied systematically. In this work, forced alkaline flocculation of the freshwater microalgae Chlorella vulgaris induced by calcium phosphate precipitates was studied as a model system. Response surface methodology was used to quantify the effect of independent variables (concentration of Ca2+ (0...
March 6, 2018: Colloids and Surfaces. B, Biointerfaces
Markus Basan
Elucidating strategies of resource allocation and metabolism is crucial for a better understanding of microbial phenotypes. In particular, uncovering the governing principles underlying these processes would be a crucial step for achieving a central aim of systems microbiology, which is to quantitatively predict phenotypes of microbial cells or entire populations in diverse conditions. Here, some of the key concepts for understanding cellular resource allocation and metabolism that have been suggested over the past years are reviewed...
March 12, 2018: Current Opinion in Microbiology
Suzanne Ostrand-Rosenberg
Myeloid-derived suppressor cells (MDSC) are present in most individuals with cancer where they inhibit adaptive and innate antitumor immunity and are an obstacle to cancer immunotherapies. Chronic inflammation is characteristic of adipose tissue and is a risk factor for the onset and progression of cancer in obese individuals. Because MDSC accumulate in response to inflammation, it has been hypothesized that one of the mechanisms by which obesity promotes malignancy is through the induction of MDSC. This article reviews the data supporting this hypothesis, the role of leptin and fatty acid metabolism in the induction of MDSC, and the surprising finding that although MDSC promote tumor progression, they are protective against some of the metabolic dysfunction associated with obesity...
March 12, 2018: Current Opinion in Immunology
Emily Wonder, Lorena Simón-Gracia, Pablo Scodeller, Ramsey N Majzoub, Venkata Ramana Kotamraju, Kai K Ewert, Tambet Teesalu, Cyrus R Safinya
Cationic liposome-nucleic acid (CL-NA) complexes, which form spontaneously, are a highly modular gene delivery system. These complexes can be sterically stabilized via PEGylation [PEG: poly (ethylene glycol)] into nanoparticles (NPs) and targeted to specific tissues and cell types via the conjugation of an affinity ligand. However, there are currently no guidelines on how to effectively navigate the large space of compositional parameters that modulate the specific and nonspecific binding interactions of peptide-targeted NPs with cells...
March 2, 2018: Biomaterials
John K Fallon, Nicole Houvig, Catherine L Booth-Genthe, Philip C Smith
Information is needed on the expression of transporters in lung to inform drug development and therapeutic decisions. Much of the information currently available is from semiquantitative gene expression or immunometric densitometry studies reported in the literature. NanoLC-MS/MS (MRM mode) isotope dilution targeted quantitative proteomics was used here to quantify twelve selected transporters in fresh human lung membrane fraction samples and in the membrane fraction of selected immortalized human lung epithelial cell line samples...
February 22, 2018: Journal of Pharmaceutical and Biomedical Analysis
Sara Sigismund, Giorgio Scita
An explosive growth in knowledge, in the last two decades, has conferred a new dimension to the process of endocytosis. Endocytic circuitries have come into focus as a pervasive system that controls virtual all aspects of cell biology. A few years ago, we proposed the term 'endocytic matrix' to define a cellular network of signalling wiring that is at the core of the cellular blueprint. A primary role of the endocytic matrix is the delivery of space-resolved and time-resolved signals to the cell in an interpretable format, and, as such, it has profound consequences on polarized cellular and supra-cellular functions, first and foremost, cell motility...
March 12, 2018: Current Opinion in Cell Biology
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