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https://www.readbyqxmd.com/read/28544883/the-limiting-pool-mechanism-fails-to-control-the-size-of-multiple-organelles
#1
Lishibanya Mohapatra, Thibaut J Lagny, David Harbage, Predrag R Jelenkovic, Jane Kondev
How the size of micrometer-scale cellular structures such as the mitotic spindle, cytoskeletal filaments, the nucleus, the nucleolus, and other non-membrane bound organelles is controlled despite a constant turnover of their constituent parts is a central problem in biology. Experiments have implicated the limiting-pool mechanism: structures grow by stochastic addition of molecular subunits from a finite pool until the rates of subunit addition and removal are balanced, producing a structure of well-defined size...
May 24, 2017: Cell Systems
https://www.readbyqxmd.com/read/28544748/carbon-monoxide-dehydrogenase-reduces-cyanate-to-cyanide
#2
Alexandre Ciaccafava, Daria Tombolelli, Lilith Domnik, Jae-Hun Jeoung, Holger Dobbek, Maria-Andrea Mroginski, Ingo Zebger, Peter Hildebrandt
The biocatalytic function of carbon monoxide dehydrogenase (CODH) has a high environmental relevance owing to its ability to reduce CO2 . Despite numerous studies on CODH over the past decades, its catalytic mechanism is not yet fully understood. In the present combined spectroscopic and theoretical study, we report first evidences for a cyanate (NCO(-) ) to cyanide (CN(-) ) reduction at the C-cluster. The adduct remains bound to the catalytic center to form the so-called CN(-) -inhibited state. Notably, this conversion does not occur in crystals of the Carboxydothermus hydrogenoformans CODH enzyme (CODHIICh ), as indicated by the lack of the corresponding CN(-) stretching mode...
May 23, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/28544674/direct-hydroxylation-of-benzene-to-phenol-by-cytochrome-p450bm3-triggered-by-amino-acid-derivatives
#3
Osami Shoji, Sota Yanagisawa, Joshua Kyle Stanfield, Kazuto Suzuki, Zhiqi Cong, Hiroshi Sugimoto, Yoshitsugu Shiro, Yoshihito Watanabe
Selective hydroxylation of benzene to phenol, without formation of side products resulting from overoxidation, was catalyzed by cytochrome P450BM3 (P450BM3) with the assistance of amino acid derivatives as decoy molecules. The catalytic turnover rate and the total turnover number reached 259 min-1P450BM3-1 and 40,200 P450BM3-1 when N-heptyl-L-proline modified with L-phenyl alanine (C7-L-Pro-L-Phe) was used as the decoy molecule. This work shows that amino acid derivatives that have a totally different structure from fatty acids can be used as decoy molecules for aromatic hydroxylation by wild-type P450BM3...
May 22, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/28544479/drinking-problems-mechanisms-of-macropinosome-formation-and-maturation
#4
REVIEW
Catherine M Buckley, Jason S King
Macropinocytosis is a mechanism for the non-specific bulk uptake and internalisation of extracellular fluid. This plays specific and distinct roles in diverse cell types such as macrophages, dendritic cells and neurons, by allowing cells to sample their environment, extract extracellular nutrients and regulate plasma membrane turnover. Macropinocytosis has recently been implicated in several diseases including cancer, neurodegenerative diseases and atherosclerosis. Uptake by macropinocytosis is also exploited by several intracellular pathogens to gain entry into host cells...
May 24, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28543873/effect-of-surgery-vs-observation-skeletal-5-year-outcomes-in-a-randomized-trial-of-patients-with-primary-hpt-the-siph-study
#5
Karolina Lundstam, Ansgar Heck, Kristin Godang, Charlotte Mollerup, Marek Baranowski, Ylva Pernow, Turid Aas, Ola Hessman, Thord Rosén, Jörgen Nordenström, Svante Jansson, Mikael Hellström, Jens Bollerslev
Mild primary hyperparathyroidism (PHPT) is known to affect the skeleton, even though patients usually are asymptomatic. Treatment strategies have been widely discussed. However, long-term randomized studies comparing parathyroidectomy to observation are lacking. The objective was to study the effect of parathyroidectomy (PTX) compared to observation (OBS) on bone mineral density (BMD) in g/cm(2) and T-scores, and on biochemical markers of bone turnover (P1NP and CTX-1), in a prospective randomized controlled study of patients with mild PHPT after 5 years of follow-up...
May 25, 2017: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
https://www.readbyqxmd.com/read/28543818/bone-formation-is-coupled-to-resorption-via-suppression-of-sclerostin-expression-by-osteoclasts
#6
Masanori Koide, Yasuhiro Kobayashi, Teruhito Yamashita, Shunsuke Uehara, Midori Nakamura, B Yukihiro Hiraoka, Yuki Ozaki, Tadahiro Iimura, Hisataka Yasuda, Naoyuki Takahashi, Nobuyuki Udagawa
Bone formation is coupled to bone resorption throughout life. However, it is not fully elucidated the coupling mechanisms. Using Tnfrsf11b-deficient (OPG(-/-) ) mice, in which bone formation is clearly coupled to bone resorption, we found here that osteoclasts suppress the expression of sclerostin, a Wnt antagonist, thereby promoting bone formation. Wnt/beta-catenin signals were higher in OPG(-/-) and RANKL-transgenic mice with a low level of sclerostin. Conditioned medium from osteoclast cultures (Ocl-CM) suppressed sclerostin expression in UMR106 cells and osteocyte cultures...
May 24, 2017: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
https://www.readbyqxmd.com/read/28543622/in-vivo-exfoliating-efficacy-of-biodegradable-beads-and-the-correlation-with-user-s-satisfaction
#7
J Kitsongsermthon, J Kreepoke, K Duangweang, A Tansirikongkol
BACKGROUND/PURPOSE: By the end of 2017, non-biodegradable microbeads will be prohibited in USA, UK and Europe, due to their environmental issue. There are biodegradable beads available, but their effect on skin desquamation has not been evaluated yet. This study aimed to understand the skin renewal time, moisturizing effect and user's satisfaction of gel scrubs containing different exfoliating beads. METHODS: Gel scrubs, containing polyethylene, mannan or wax beads, were used in this study...
May 24, 2017: Skin Research and Technology
https://www.readbyqxmd.com/read/28542550/a-spatio-temporal-assessment-of-simian-human-immunodeficiency-virus-shiv-evolution-reveals-a-highly-dynamic-process-within-the-host
#8
Alison F Feder, Christopher Kline, Patricia Polacino, Mackenzie Cottrell, Angela D M Kashuba, Brandon F Keele, Shiu-Lok Hu, Dmitri A Petrov, Pleuni S Pennings, Zandrea Ambrose
The process by which drug-resistant HIV-1 arises and spreads spatially within an infected individual is poorly understood. Studies have found variable results relating how HIV-1 in the blood differs from virus sampled in tissues, offering conflicting findings about whether HIV-1 throughout the body is homogeneously distributed. However, most of these studies sample only two compartments and few have data from multiple time points. To directly measure how drug resistance spreads within a host and to assess how spatial structure impacts its emergence, we examined serial sequences from four macaques infected with RT-SHIVmne027, a simian immunodeficiency virus encoding HIV-1 reverse transcriptase (RT), and treated with RT inhibitors...
May 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28542371/whole-genome-sequencing-of-spermatocytic-tumors-provides-insights-into-the-mutational-processes-operating-in-the-male-germline
#9
Eleni Giannoulatou, Geoffrey J Maher, Zhihao Ding, Ad J M Gillis, Lambert C J Dorssers, Alexander Hoischen, Ewa Rajpert-De Meyts, Gilean McVean, Andrew O M Wilkie, Leendert H J Looijenga, Anne Goriely
Adult male germline stem cells (spermatogonia) proliferate by mitosis and, after puberty, generate spermatocytes that undertake meiosis to produce haploid spermatozoa. Germ cells are under evolutionary constraint to curtail mutations and maintain genome integrity. Despite constant turnover, spermatogonia very rarely form tumors, so-called spermatocytic tumors (SpT). In line with the previous identification of FGFR3 and HRAS selfish mutations in a subset of cases, candidate gene screening of 29 SpTs identified an oncogenic NRAS mutation in two cases...
2017: PloS One
https://www.readbyqxmd.com/read/28541576/rapidly-evolving-toll-3-4-genes-encode-male-specific-toll-like-receptors-in-drosophila
#10
Tera C Levin, Harmit S Malik
Animal Toll-like receptors (TLRs) have evolved through a pattern of duplication and divergence. Whereas mammalian TLRs directly recognize microbial ligands, Drosophila Tolls bind endogenous ligands downstream of both developmental and immune signaling cascades. Here, we find that most Toll genes in Drosophila evolve slowly with little gene turnover (gains/losses), consistent with their important roles in development and indirect roles in microbial recognition. In contrast, we find that the Toll-3/4 genes have experienced an unusually rapid rate of gene gains and losses, resulting in lineage-specific Toll-3/4s and vastly different gene repertoires among Drosophila species, from zero copies (e...
May 25, 2017: Molecular Biology and Evolution
https://www.readbyqxmd.com/read/28541473/relationship-between-synaptic-ampar-and-spine-dynamics-impairments-in-the-fxs-mouse
#11
Anand Suresh, Anna Dunaevsky
Structural dynamics of dendritic spines are important for memory and learning and are impaired in neurodevelopmental disorders such as fragile X syndrome. Spine dynamics are regulated by activity-dependent mechanisms that involve modulation of AMPA receptors (AMPAR); however, the relationship between AMPAR and spine dynamics in vivo and how these are altered in FXS mouse model is not known. Here, we tracked AMPAR and spines over multiple days in vivo in the cortex and found that dendritic spines in the fmr1 KO mouse were denser, smaller, had higher turnover rates and contained less sGluA2 compared to littermate controls...
May 24, 2017: Cerebral Cortex
https://www.readbyqxmd.com/read/28541290/tailoring-nanoscopic-confines-to-maximize-catalytic-activity-of-hydronium-ions
#12
Hui Shi, Sebastian Eckstein, Aleksei Vjunov, Donald M Camaioni, Johannes A Lercher
Acid catalysis by hydronium ions is ubiquitous in aqueous-phase organic reactions. Here we show that hydronium ion catalysis, exemplified by intramolecular dehydration of cyclohexanol, is markedly influenced by steric constraints, yielding turnover rates that increase by up to two orders of magnitude in tight confines relative to an aqueous solution of a Brønsted acid. The higher activities in zeolites BEA and FAU than in water are caused by more positive activation entropies that more than offset higher activation enthalpies...
May 25, 2017: Nature Communications
https://www.readbyqxmd.com/read/28541049/synthesis-and-photophysical-and-photocatalytic-properties-of-a-highly-fluorinated-and-durable-phthalocyanine-peptide-bioconjugate-for-potential-theranostic-applications
#13
Erik N Carrión, Jenyffer Santiago, David Sabatino, Sergiu M Gorun
The functionalized, asymmetric fluoro-fluoroalkyl scaffold F48H7COOHPcZn (3) was used to prepare F48H7COOPcZn-6-amino-hexanoate-CTVALPGGYVRVC (5), a Pep42 peptide bioconjugate envisioned for photodynamic therapy, which can specifically target the GRP78 chaperone protein overexpressed and exclusively localized on some cancer cell surfaces. The analogous F48H7COOHPcCu (4) has also been prepared, and its single-crystal X-ray structure was elucidated. Despite reduced steric hindrance relative to the nonfunctionalized, single-site complexes of the F64Pc scaffold, no aggregation was detected in solution via UV-vis spectroscopy, for either 3, 4, or 5, consistent with the lack of π stacking observed for the crystalline 4...
May 25, 2017: Inorganic Chemistry
https://www.readbyqxmd.com/read/28540603/positioning-novel-biologicals-in-ckd-mineral-and-bone-disorders
#14
REVIEW
Lida Tartaglione, Marzia Pasquali, Silverio Rotondi, Maria Luisa Muci, Adrian Covic, Sandro Mazzaferro
Renal osteodystrophy (ROD), the histologic bone lesions of chronic kidney disease (CKD), is now included in a wider syndrome with laboratory abnormalities of mineral metabolism and extra-skeletal calcifications or CKD-mineral and bone disorders (CKD-MBD), to highlight the increased burden of mortality. Aging people, frequently identified as early CKD, could suffer from either the classical age-related osteoporosis (OP) or ROD. Distinguishing between these two bone diseases may not be easy without bone biopsy...
May 24, 2017: Journal of Nephrology
https://www.readbyqxmd.com/read/28540505/retrospective-evaluation-of-serum-ctx-levels-after-denosumab-discontinuation-in-patients-with-or-without-prior-exposure-to-bisphosphonates
#15
B Uebelhart, R Rizzoli, S L Ferrari
Discontinuation of denosumab (Dmab) therapy is associated with lower serum CTX levels in osteoporotic patients previously exposed to bisphosphonates compared to those who were not. INTRODUCTION: Discontinuation of Dmab therapy is followed by a transient increase of bone turnover markers (BTMs) above pretreatment values, together with accelerated bone loss, and potentially an increased risk of multiple vertebral fractures. Since a substantial proportion of patients discontinuing Dmab have previously been exposed to bisphosphonates (BPs), we hypothesized that previous BP therapy could attenuate this increase in bone turnover because of the prolonged biological effects of BPs on bone...
May 24, 2017: Osteoporosis International
https://www.readbyqxmd.com/read/28539825/effects-of-c-reactive-protein-on-the-expression-of-matrix-metalloproteinases-and-their-inhibitors-via-fc%C3%AE-receptors-on-3t3-l1-adipocytes
#16
Kumiko Nakai, Hideki Tanaka, Kazuhiro Yamanaka, Yumi Takahashi, Fumiko Murakami, Rieko Matsuike, Jumpei Sekino, Natsuko Tanabe, Toyoko Morita, Yoji Yamazaki, Takayuki Kawato, Masao Maeno
The association between obesity and inflammation is well documented in epidemiological studies. Proteolysis of extracellular matrix (ECM) proteins is involved in adipose tissue enlargement, and matrix metalloproteinases (MMPs) collectively cleave all ECM proteins. Here, we examined the effects of C-reactive protein (CRP), an inflammatory biomarker, on the expression of MMPs and tissue inhibitors of metalloproteinases (TIMPs), which are natural inhibitors of MMPs, in adipocyte-differentiated 3T3-L1 cells. We analyzed the expression of Fcγ receptor (FcγR) IIb and FcγRIII, which are candidates for CRP receptors, and the effects of anti-CD16/CD32 antibodies, which can act as FcγRII and FcγRIII blockers on CRP-induced alteration of MMP and TIMP expression...
2017: International Journal of Medical Sciences
https://www.readbyqxmd.com/read/28539521/harvest-and-group-effects-on-pup-survival-in-a-cooperative-breeder
#17
David E Ausband, Michael S Mitchell, Carisa R Stansbury, Jennifer L Stenglein, Lisette P Waits
Recruitment in cooperative breeders can be negatively affected by changes in group size and composition. The majority of cooperative breeding studies have not evaluated human harvest; therefore, the effects of recurring annual harvest and group characteristics on survival of young are poorly understood. We evaluated how harvest and groups affect pup survival using genetic sampling and pedigrees for grey wolves in North America. We hypothesized that harvest reduces pup survival because of (i) reduced group size, (ii) increased breeder turnover and/or (iii) reduced number of female helpers...
May 31, 2017: Proceedings. Biological Sciences
https://www.readbyqxmd.com/read/28539462/horizontal-and-vertical-species-turnover-in-tropical-birds-in-habitats-with-differing-land-use
#18
Rachakonda Sreekar, Richard T Corlett, Salindra Dayananda, Uromi Manage Goodale, Adam Kilpatrick, Sarath W Kotagama, Lian Pin Koh, Eben Goodale
Large tracts of tropical rainforests are being converted into intensive agricultural lands. Such anthropogenic disturbances are known to reduce species turnover across horizontal distances. But it is not known if they can also reduce species turnover across vertical distances (elevation), which have steeper climatic differences. We measured turnover in birds across horizontal and vertical sampling transects in three land-use types of Sri Lanka: protected forest, reserve buffer and intensive-agriculture, from 90 to 2100 m a...
May 2017: Biology Letters
https://www.readbyqxmd.com/read/28539410/leishmania-donovani-restricts-mitochondrial-dynamics-to-enhance-mirnp-stability-and-target-rna-repression-in-host-macrophages
#19
Yogaditya Chakrabarty, Suvendra N Bhattacharyya
microRNAs (miRNA), the tiny regulatory RNAs, form complex with Argonaute (Ago) proteins and inhibit gene expression in metazoan cells. While studying parasite invaded macrophages, we have identified a unique mode of gene regulation, where the parasite Leishmania donovani (Ld) causes mitochondrial depolarization, reduces mitochondrial dynamics and restricts turnover of cellular microRNA ribonucleoprotein (miRNP) complexes in infected host cells. This leads to increased stability of miRNPs along with elevated level of Ago2 bound cytokine mRNA in Ld infected macrophages...
May 24, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28539401/transmembrane-helix-hydrophobicity-is-an-energetic-barrier-during-the-retrotranslocation-of-integral-membrane-erad-substrates
#20
Christopher J Guerriero, Karl-Richard Reutter, Andrew A Augustine, G Michael Preston, Kurt F Weiberth, Timothy D Mackie, Hillary C Cleveland-Rubeor, Neville P Bethel, Keith M Callenberg, Kunio Nakatsukasa, Michael Grabe, Jeffrey L Brodsky
Integral membrane proteins fold inefficiently and are susceptible to turnover via the endoplasmic reticulum-associated degradation (ERAD) pathway. During ERAD, misfolded proteins are recognized by molecular chaperones, polyubiquitinated, and retrotranslocated to the cytoplasm for proteasomal degradation. Although many aspects of this pathway are defined, how transmembrane helices (TMHs) are removed from the membrane and into the cytoplasm prior to degradation is poorly understood. In this study, we asked whether the hydrophobic character of a TMH acts as an energetic barrier to retrotranslocation...
May 24, 2017: Molecular Biology of the Cell
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