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https://www.readbyqxmd.com/read/28708998/profiling-ssb-nascent-chain-interactions-reveals-principles-of-hsp70-assisted-folding
#1
Kristina Döring, Nabeel Ahmed, Trine Riemer, Harsha Garadi Suresh, Yevhen Vainshtein, Markus Habich, Jan Riemer, Matthias P Mayer, Edward P O'Brien, Günter Kramer, Bernd Bukau
The yeast Hsp70 chaperone Ssb interacts with ribosomes and nascent polypeptides to assist protein folding. To reveal its working principle, we determined the nascent chain-binding pattern of Ssb at near-residue resolution by in vivo selective ribosome profiling. Ssb associates broadly with cytosolic, nuclear, and hitherto unknown substrate classes of mitochondrial and endoplasmic reticulum (ER) nascent proteins, supporting its general chaperone function. Ssb engages most substrates by multiple binding-release cycles to a degenerate sequence enriched in positively charged and aromatic amino acids...
July 13, 2017: Cell
https://www.readbyqxmd.com/read/28707599/designing-of-selective-%C3%AE-secretase-inhibitory-benzenesulfonamides-through-comparative-in-vitro-and-in-silico-analysis
#2
Neeraj Masand, Satya P Gupta, Ratan Lal Khosa
BACKGROUND: In Alzheimer's disease (AD), the gene mutations have been identified in the amyloid precursor protein (APP), the presenilin-1 (PS1) and -2 (PS2) genes. APP is a transmembrane protein which gets cleaved by α- and β-secretase enzymes and releases Aβ peptides which forms senile plaques in brain tissue. It contributes for local inflammatory response, subsequent oxidative stress, biochemical changes and neuronal death. Targeting the development of Aβ aggregates in the senile plaques is an important strategy in the treatment of AD...
July 13, 2017: Current Drug Discovery Technologies
https://www.readbyqxmd.com/read/28704538/intestinal-calcium-and-bile-salts-facilitate-germination-of-clostridium-difficile-spores
#3
Travis J Kochan, Madeline J Somers, Alyssa M Kaiser, Michelle S Shoshiev, Ada K Hagan, Jessica L Hastie, Nicole P Giordano, Ashley D Smith, Alyxandria M Schubert, Paul E Carlson, Philip C Hanna
Clostridium difficile (C. difficile) is an anaerobic gram-positive pathogen that is the leading cause of nosocomial bacterial infection globally. C. difficile infection (CDI) typically occurs after ingestion of infectious spores by a patient that has been treated with broad-spectrum antibiotics. While CDI is a toxin-mediated disease, transmission and pathogenesis are dependent on the ability to produce viable spores. These spores must become metabolically active (germinate) in order to cause disease. C. difficile spore germination occurs when spores encounter bile salts and other co-germinants within the small intestine, however, the germination signaling cascade is unclear...
July 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28700952/nicotine-facilitates-nicotinic-acetylcholine-receptor-targeting-to-mitochondria-but-makes-them-less-susceptible-to-selective-ligands
#4
Kateryna Uspenska, Olena Lykhmus, Galyna Gergalova, Volodymyr Chernyshov, Hugo R Arias, Sergiy Komisarenko, Maryna Skok
Several nicotinic acetylcholine receptor (nAChR) subtypes are expressed in mitochondria to regulate the internal pathway of apoptosis in ion channel-independent manner. However, the mechanisms of nAChR activation in mitochondria and targeting to mitochondria are still unknown. Nicotine has been shown to favor nAChR pentamer assembly, folding, and maturation on the way of biosynthesis. The idea of the present work was to determine whether nicotine affects the content, glycosylation, and function of mitochondrial nAChRs...
July 9, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28698291/bioprosthetic-valve-fracture-improves-the-hemodynamic-results-of-valve-in-valve-transcatheter-aortic-valve-replacement
#5
Adnan K Chhatriwalla, Keith B Allen, John T Saxon, David J Cohen, Sanjeev Aggarwal, Anthony J Hart, Suzanne J Baron, Danny Dvir, A Michael Borkon
BACKGROUND: Valve-in-valve (VIV) transcatheter aortic valve replacement (TAVR) may be less effective in small surgical valves because of patient/prosthesis mismatch. Bioprosthetic valve fracture (BVF) using a high-pressure balloon can be performed to facilitate VIV TAVR. METHODS AND RESULTS: We report data from 20 consecutive clinical cases in which BVF was successfully performed before or after VIV TAVR by inflation of a high-pressure balloon positioned across the valve ring during rapid ventricular pacing...
July 2017: Circulation. Cardiovascular Interventions
https://www.readbyqxmd.com/read/28678065/pregnancy-and-reproductive-aspects-of-systemic-lupus-erythematosus
#6
Laura Andreoli, Francesca Crisafulli, Angela Tincani
PURPOSE OF REVIEW: To discuss pregnancy and reproductive aspects in women with systemic lupus erythematosus (SLE) with particular focus on preconception counselling, maternal and foetal outcomes, safety and beneficial effects of drugs during pregnancy as well as contraception methods, assisted reproduction techniques and strategies for thromboembolism prophylaxis in patients with positive antiphospholipid antibodies. RECENT FINDINGS: Evidence-based recommendations for the management of family planning and women's health issues in SLE and/or APS have been developed by a multidisciplinary panel of experts...
July 3, 2017: Current Opinion in Rheumatology
https://www.readbyqxmd.com/read/28673596/intra-spinal-microstimulation-may-alleviate-chronic-pain-after-spinal-cord-injury
#7
Bin Shu, Fei Yang, Yun Guan
Chronic pain after spinal cord injury (SCI) is a form of central neuropathic pain that is debilitating and often refractory to current pharmacological treatments. Neurostimulation pain therapies, such as epidural spinal cord stimulation, have only moderate success in reducing SCI pain. The pathogenesis of SCI pain may involve a state of central neuronal hyperexcitability, especially in the spinal cord dorsal horn, that develops after injury. We hypothesize that the neuronal structures near the spinal cord injury site may be an important pain generator, and intraspinal microstimulation (ISMS) may normalize dorsal horn neuronal hyperexcitability and hence alleviate SCI pain...
July 2017: Medical Hypotheses
https://www.readbyqxmd.com/read/28662899/l-type-amino-acid-transporter-1-utilizing-prodrugs-how-to-achieve-effective-brain-delivery-and-low-systemic-exposure-of-drugs
#8
Elena Puris, Mikko Gynther, Johanna Huttunen, Aleksanteri Petsalo, Kristiina M Huttunen
L-type amino acid transporter 1 (LAT1) is selectively expressed in the blood-brain barrier (BBB) and brain parenchyma. This transporter can facilitate brain delivery of neuroprotective agents and additionally give opportunity to minimize systemic exposure. Here, we investigated structure-pharmacokinetics relationship of five newly synthesized LAT1-utilizing prodrugs of the cyclooxygenase inhibitor, ketoprofen, in order to identify beneficial structural features of prodrugs to achieve both targeted brain delivery and low peripheral distribution of the parent drug...
June 27, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28661068/expression-of-mir-18a-and-mir-34c-in-circulating-monocytes-associated-with-vulnerability-to-type-2-diabetes-mellitus-and-insulin-resistance
#9
Si-Si Wang, Yong-Qiang Li, Ying-Zhi Liang, Jing Dong, Yan He, Ling Zhang, Yu-Xiang Yan
Chronic stress may facilitate the development of metabolic disorders including insulin resistance (IR) and type 2 diabetes mellitus (T2DM). MiR-18a and miR-34c modulate central cell responsiveness to stress by targeting glucocorticoid receptor (GR) and corticotropin-releasing factor receptor type 1 (CRFR1) mRNA, which are important regulators of the hypothalamus-pituitary-adrenal (HPA) axis. This study explored the relationship between T2DM/IR and expression of miR-18a and miR-34c in peripheral blood mononuclear cells (PBMCs) in an occupational sample...
June 29, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28652278/palbociclib-combined-with-fulvestrant-in-premenopausal-women-with-advanced-breast-cancer-and-prior-progression-on-endocrine-therapy-paloma-3-results
#10
Sibylle Loibl, Nicholas C Turner, Jungsil Ro, Massimo Cristofanilli, Hiroji Iwata, Seock-Ah Im, Norikazu Masuda, Sherene Loi, Fabrice André, Nadia Harbeck, Sunil Verma, Elizabeth Folkerd, Kathy Puyana Theall, Justin Hoffman, Ke Zhang, Cynthia Huang Bartlett, Mitchell Dowsett
BACKGROUND: The efficacy and safety of palbociclib, a cyclin-dependent kinase 4/6 inhibitor, combined with fulvestrant and goserelin was assessed in premenopausal women with advanced breast cancer (ABC) who had progressed on prior endocrine therapy (ET). PATIENTS AND METHODS: One hundred eight premenopausal endocrine-refractory women ≥18 years with hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) ABC were among 521 women randomized 2:1 (347:174) to fulvestrant (500 mg) ± goserelin with either palbociclib (125 mg/day orally, 3 weeks on, 1 week off) or placebo...
June 26, 2017: Oncologist
https://www.readbyqxmd.com/read/28643513/photochemical-cleavage-of-benzylic-c-o-bond-facilitated-by-an-ortho-or-meta-amino-group
#11
Xiong Ding, Pengfei Wang
The excited state meta effect, also known as the meta-ortho effect, results from selective electron transmission from an electron-donating group to the meta and ortho sites on an aromatic ring in its first excited singlet state. This effect facilitates photochemical cleavage of benzylic C-O or C-N bond to release the corresponding alcohol, carboxylic acid, or amine when an electron-donating amino group is at the meta position, as demonstrated in our recent work of using a 3-diethylaminobenzyl (DEABn) group as an effective photolabile protecting group (PPG)...
June 23, 2017: Journal of Organic Chemistry
https://www.readbyqxmd.com/read/28642617/podoplanin-enhances-lung-cancer-cell-growth-in-vivo-by-inducing-platelet-aggregation
#12
Kenichi Miyata, Ai Takemoto, Sakae Okumura, Makoto Nishio, Naoya Fujita
Podoplanin/Aggrus, known as a platelet aggregation-inducing factor, is frequently overexpressed in lung squamous cell carcinomas (LSCC) and glioblastomas among other tumours, and its expression has been reported to be correlated with poor prognosis. However, the contribution of podoplanin to malignant progression has been elusive. Here we demonstrate that in podoplanin-positive LSCC cells, their growth was abrogated by podoplanin knockout in vivo but not in vitro. Conversely, ectopic expression of podoplanin promoted cell growth in vivo and facilitated intratumoral platelet activation...
June 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28631442/osteoblast-migration-in-vertebrate-bone
#13
Antonia Thiel, Marie K Reumann, Adele Boskey, Johannes Wischmann, Rüdiger von Eisenhart-Rothe, Philipp Mayer-Kuckuk
Bone formation, for example during bone remodelling or fracture repair, requires mature osteoblasts to deposit bone with remarkable spatial precision. As osteoblast precursors derive either from circulation or resident stem cell pools, they and their progeny are required to migrate within the three-dimensional bone space and to navigate to their destination, i.e. to the site of bone formation. An understanding of this process is emerging based on in vitro and in vivo studies of several vertebrate species. Receptors on the osteoblast surface mediate cell adhesion and polarization, which induces osteoblast migration...
June 19, 2017: Biological Reviews of the Cambridge Philosophical Society
https://www.readbyqxmd.com/read/28624237/identification-of-syntaxin-4-as-an-essential-factor-for-the-hepatitis-c-virus-life-cycle
#14
Huimei Ren, Fabian Elgner, Kiyoshi Himmelsbach, Sami Akhras, Bingfu Jiang, Regina Medvedev, Daniela Ploen, Eberhard Hildt
Although there is evidence that multivesicular bodies (MVBs) are involved in the release of hepatitis C virus (HCV), many aspects of HCV release are still not fully understood. The amount of α-taxilin that prevents SNARE (soluble N-ethylmaleimidesensitive factor attachment protein receptor) complex formation by binding to free syntaxin 4 is reduced in HCV-positive cells. Therefore, it was analyzed whether the t-SNARE protein syntaxin 4 which mediates vesicles fusion is involved in the HCV life cycle. HCV-positive cells possess an increased amount of syntaxin 4 protein, although the amount of syntaxin 4-specific transcripts is decreased in HCV-positive Huh7...
June 10, 2017: European Journal of Cell Biology
https://www.readbyqxmd.com/read/28618866/characterization-of-articular-cartilage-recovery-and-its-correlation-with-optical-response-in-the-near-infrared-spectral-range
#15
Isaac Oluwaseun Afara, Sanjleena Singh, Hayley Moody, Lihai Zhang, Adekunle Oloyede
OBJECTIVES: In this study, we examine the capacity of a new parameter, based on the recovery response of articular cartilage, to distinguish between healthy and damaged tissues. We also investigate whether or not this new parameter correlates with the near-infrared (NIR) optical response of articular cartilage. DESIGN: Normal and artificially degenerated (proteoglycan-depleted) bovine cartilage samples were nondestructively probed using NIR spectroscopy. Subsequently they were subjected to a load and unloading protocol, and the recovery response was logged during unloading...
July 2017: Cartilage
https://www.readbyqxmd.com/read/28615206/plasticity-and-epitope-exposure-of-the-hiv-1-envelope-trimer
#16
Rebecca L R Powell, Maxim Totrov, Vincenza Itri, Xiaomei Liu, Alisa Fox, Susan Zolla-Pazner
We recently showed that mutations in the HIV-1 Envelope (Env) destabilize the V3 loop, rendering neutralization-resistant viruses sensitive to V3-directed monoclonal antibodies (mAbs). Here we investigated the propagation of this effect on other Env epitopes, with special emphasis on V2 loop exposure. Wildtype JR-FL and 19 mutant JR-FL pseudoviruses were tested for neutralization sensitivity to 21 mAbs specific for epitopes in V2, the CD4 binding site (CD4bs), and the CD4-induced (CD4i) region. Certain glycan mutants, mutations in the gp120 hydrophobic core, and mutations in residues involved in intra-protomer interactions exposed epitopes in the V2i region (overlays the α4β7 integrin binding site) and the V3 crown, suggesting a general destabilization of the distal region of the trimer apex...
June 14, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28607107/myeloid-sirtuin-6-deficiency-causes-insulin-resistance-in-high-fat-diet-fed-mice-by-eliciting-macrophage-polarization-toward-an-m1-phenotype
#17
Youngyi Lee, Sun-O Ka, Hye-Na Cha, Yu-Na Chae, Mi-Kyung Kim, So-Young Park, Eun Ju Bae, Byung-Hyun Park
Obesity-related insulin resistance is closely associated with macrophage accumulation and subsequent cytokine release in local tissues. Sirtuin (Sirt) 6 is known to exert an anti-inflammatory function but its role in macrophages in the context of obesity has not been investigated. Here, we generated myeloid-specific Sirt6 knockout mice (mS6KO) and investigated the metabolic characteristics after high-fat diet (HFD) feeding for 16 weeks. Compared with their wild type littermates, HFD-fed mS6KO mice exhibited greater increases in body weight, fasting blood glucose- and insulin-levels, hepatic steatosis, glucose intolerance, and insulin resistance...
June 12, 2017: Diabetes
https://www.readbyqxmd.com/read/28606810/tailored-design-of-multifunctional-and-programmable-ph-responsive-self-assembling-polypeptides-as-drug-delivery-nanocarrier-for-cancer-therapy
#18
Tzu-Wei Wang, Chia-Wei Yeh, Chen-Hsiang Kuan, Li-Wen Wang, Liang-Hsin Chen, Hsi-Chin Wu, Jui-Shen Sun
Breast cancer has become the second leading cause of cancer-related mortality in female wherein more than 90% of breast cancer-related death results from cancer metastasis to distant organs at advanced stage. The purpose of this study is to develop biodegradable nanoparticles composed of natural polypeptides and calcium phosphate (CaP) with sequential pH-responsivity to tumor microenvironments for active targeted drug delivery. Two different amphiphilic copolymers, poly(ethylene glycol)3400-aconityl linkage-poly(l-glutamic acid)15-poly(l-histidine)10-poly(l-leucine)10 and LyP1-poly(ethylene glycol)1100-poly(l-glutamic acid)15-poly(l-histidine)10-poly(l-leucine)10, were exploited to self-assemble into micelles in aqueous phase...
June 9, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/28597100/sucrose-induced-plasticity-in-the-basolateral-amygdala-in-a-comfort-feeding-paradigm
#19
Amy E B Packard, Shi Di, Ann E Egan, Sarah M Fourman, Jeffrey G Tasker, Yvonne M Ulrich-Lai
A history of intermittent, limited sucrose intake (LSI) attenuates the hypothalamic-pituitary-adrenocortical (HPA) axis stress response, and neuronal activity in the basolateral amygdala (BLA) is necessary for this HPA-dampening. LSI increases the expression of plasticity-associated genes in the BLA; however, the nature of this plasticity is unknown. As BLA principal neuron activity normally promotes HPA responses, the present study tests the hypothesis that LSI decreases stress-excitatory BLA output by decreasing glutamatergic and/or increasing GABAergic inputs to BLA principal neurons...
June 8, 2017: Brain Structure & Function
https://www.readbyqxmd.com/read/28595136/janus-silver-mesoporous-silica-nanobullets-with-synergistic-antibacterial-functions
#20
Zhi-Min Chang, Zheng Wang, Meng-Meng Lu, Dan Shao, Juan Yue, Dian Yang, Ming-Qiang Li, Wen-Fei Dong
In this study, we exploited a one-pot method to fabricate cetyltrimethylammonium bromide (CTAB)-loaded Janus silver mesoporous silica nanoparticles (Janus Ag-MSNs@CTAB). These bullet-like nanoparticles had a silver head (80nm in diameter) attached to a mesoporous silica stick (200-300nm in length). The CTAB-loaded nanobullets exhibited a marked affinity for the bacterial cell surface and the simultaneously sustained release behavior of CTAB and silver ions. The minimum inhibitory concentrations (MIC) of Janus Ag-MSNs@CTAB were determined to be 10μg/mL and 20μg/mL for E...
June 4, 2017: Colloids and Surfaces. B, Biointerfaces
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