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https://www.readbyqxmd.com/read/28346524/rare-mutations-and-potentially-damaging-missense-variants-in-genes-encoding-fibrillar-collagens-and-proteins-involved-in-their-production-are-candidates-for-risk-for-preterm-premature-rupture-of-membranes
#1
Bhavi P Modi, Maria E Teves, Laurel N Pearson, Hardik I Parikh, Piya Chaemsaithong, Nihar U Sheth, Timothy P York, Roberto Romero, Jerome F Strauss
Preterm premature rupture of membranes (PPROM) is the leading identifiable cause of preterm birth with ~ 40% of preterm births being associated with PPROM and occurs in 1% - 2% of all pregnancies. We hypothesized that multiple rare variants in fetal genes involved in extracellular matrix synthesis would associate with PPROM, based on the assumption that impaired elaboration of matrix proteins would reduce fetal membrane tensile strength, predisposing to unscheduled rupture. We performed whole exome sequencing (WES) on neonatal DNA derived from pregnancies complicated by PPROM (49 cases) and healthy term deliveries (20 controls) to identify candidate mutations/variants...
2017: PloS One
https://www.readbyqxmd.com/read/28346455/collective-helicity-switching-of-a-dna-coat-assembly
#2
Yongju Kim, Huichang Li, Ying He, Xi Chen, Xiaoteng Ma, Myongsoo Lee
Hierarchical assemblies of biomolecular subunits can carry out versatile tasks at the cellular level with remarkable spatial and temporal precision. As an example, the collective motion and mutual cooperation between complex protein machines mediate essential functions for life, such as replication, synthesis, degradation, repair and transport. Nucleic acid molecules are far less dynamic than proteins and need to bind to specific proteins to form hierarchical structures. The simplest example of these nucleic acid-based structures is provided by a rod-shaped tobacco mosaic virus, which consists of genetic material surrounded by coat proteins...
March 27, 2017: Nature Nanotechnology
https://www.readbyqxmd.com/read/28346365/an-amylase-like-protein-amyd-is-the-major-negative-regulator-for-%C3%AE-glucan-synthesis-in-aspergillus-nidulans-during-the-asexual-life-cycle
#3
Xiaoxiao He, Shengnan Li, Susan Kaminskyj
α-Glucan affects fungal cell-cell interactions and is important for the virulence of pathogenic fungi. Interfering with production of α-glucan could help to prevent fungal infection. In our previous study, we reported that an amylase-like protein, AmyD, could repress α-glucan accumulation in Aspergillus nidulans. However, the underlying molecular mechanism was not clear. Here, we examined the localization of AmyD and found it was a membrane-associated protein. We studied AmyD function in α-glucan degradation, as well as with other predicted amylase-like proteins and three annotated α-glucanases...
March 27, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28345656/structure-and-function-of-the-zika-virus-full-length-ns5-protein
#4
Baoyu Zhao, Guanghui Yi, Fenglei Du, Yin-Chih Chuang, Robert C Vaughan, Banumathi Sankaran, C Cheng Kao, Pingwei Li
The recent outbreak of Zika virus (ZIKV) has infected over 1 million people in over 30 countries. ZIKV replicates its RNA genome using virally encoded replication proteins. Nonstructural protein 5 (NS5) contains a methyltransferase for RNA capping and a polymerase for viral RNA synthesis. Here we report the crystal structures of full-length NS5 and its polymerase domain at 3.0 Å resolution. The NS5 structure has striking similarities to the NS5 protein of the related Japanese encephalitis virus. The methyltransferase contains in-line pockets for substrate binding and the active site...
March 27, 2017: Nature Communications
https://www.readbyqxmd.com/read/28345463/computational-and-mechanistic-studies-on-the-effect-of-galactoxyloglucan-imatinib-nanoconjugate-in-imatinib-resistant-k562-cells
#5
Alphy Rose James, B S Unnikrishnan, R Priya, Manu M Joseph, T K Manojkumar, K Raveendran Pillai, R Shiji, G U Preethi, P Kusumakumary, T T Sreelekha
Imatinib mesylate, a BCR/ABL fusion protein inhibitor, is the first-line treatment against chronic myelogenous leukemia. In spite of its advantageous viewpoints, imatinib still has genuine impediments like undesirable side effects and tumor resistance during chemotherapy. Nanoparticles with sustainable release profile will help in targeted delivery of anticancer drugs while minimizing deleterious side effects and drug resistance. The use of biopolymers like galactoxyloglucan (PST001) for the fabrication of imatinib mesylate nanoparticles could impart its use in overcoming multidrug resistance in chronic myelogenous leukemia patients with minimal side effects...
March 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28345161/a-decrease-in-eukaryotic-elongation-factor-2-phosphorylation-is-required-for-local-translation-of-sensorin-and-long-term-facilitation-in-aplysia
#6
Patrick K McCamphill, Larissa Ferguson, Wayne S Sossin
Mechanistic target of rapamycin complex 1 (mTORC1)-dependent protein synthesis is required for many forms of synaptic plasticity and memory, but the downstream pathways important for synaptic plasticity are poorly understood. Long-term facilitation (LTF) in Aplysia is a form of synaptic plasticity that is closely linked to behavioural memory and an attractive model system for examining the important downstream targets for mTORC1 in regulating synaptic plasticity. While mTORC1 regulated protein synthesis has been strongly linked to translation initiation, translation elongation is also regulated by mTORC1 and LTF leads to an mTORC1 dependent decrease in eukaryotic elongation factor 2 (eEF2) phosphorylation...
March 27, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28344782/la-related-protein-6-controls-ciliated-cell-differentiation
#7
Zarko Manojlovic, Ryan Earwood, Akiko Kato, Diana Perez, Oscar A Cabrera, Ruth Didier, Timothy L Megraw, Branko Stefanovic, Yoichi Kato
BACKGROUND: La-related protein 6 (LARP6) is an evolutionally conserved RNA-binding protein. Vertebrate LARP6 binds the 5' stem-loop found in mRNAs encoding type I collagen to regulate their translation, but other target mRNAs and additional functions for LARP6 are unknown. The aim of this study was to elucidate an additional function of LARP6 and to evaluate the importance of its function during development. METHODS: To uncover the role of LARP6 in development, we utilized Morpholino Oligos to deplete LARP6 protein in Xenopus embryos...
2017: Cilia
https://www.readbyqxmd.com/read/28344547/app-function-and-lipids-a-bidirectional-link
#8
REVIEW
Marcus O W Grimm, Janine Mett, Heike S Grimm, Tobias Hartmann
Extracellular neuritic plaques, composed of aggregated amyloid-β (Aβ) peptides, are one of the major histopathological hallmarks of Alzheimer's disease (AD), a progressive, irreversible neurodegenerative disorder and the most common cause of dementia in the elderly. One of the most prominent risk factor for sporadic AD, carrying one or two aberrant copies of the apolipoprotein E (ApoE) ε4 alleles, closely links AD to lipids. Further, several lipid classes and fatty acids have been reported to be changed in the brain of AD-affected individuals...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28343755/covalently-linked-kanamycin-ciprofloxacin-hybrid-antibiotics-as-a-tool-to-fight-bacterial-resistance
#9
Michal Shavit, Varvara Pokrovskaya, Valery Belakhov, Timor Baasov
To address the growing problem of antibiotic resistance, a set of 12 hybrid compounds that covalently link fluoroquinolone (ciprofloxacin) and aminoglycoside (kanamycin A) antibiotics were synthesized, and their activity was determined against both Gram-negative and Gram-positive bacteria, including resistant strains. The hybrids were antagonistic relative to the ciprofloxacin, but were substantially more potent than the parent kanamycin against Gram-negative bacteria, and overcame most dominant resistance mechanisms to aminoglycosides...
March 16, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28342963/new-insights-into-cellular-cholesterol-acquisition-promoter-analysis-of-human-hmgcr-and-sqle-two-key-control-enzymes-in-cholesterol-synthesis
#10
Vicky Howe, Laura J Sharpe, Anika V Prabhu, Andrew J Brown
BACKGROUND: The two control points of cholesterol synthesis, 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) and squalene monooxygenase (SQLE) are known targets of the transcription factor sterol-regulatory element binding protein-2 (SREBP-2). Yet the location of the sterol-regulatory elements (SREs) and cofactor binding sites, nuclear factor-Y (NF-Y) and specificity protein 1 (Sp1), have not been satisfactorily mapped in the human SQLE promoter, or at all in the human HMGCR promoter...
March 22, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28342451/tert-promoter-mutations-in-telomere-biology
#11
REVIEW
Barbara Heidenreich, Rajiv Kumar
Telomere repeats at chromosomal ends, critical to genome integrity, are maintained through an elaborate network of proteins and pathways. Shelterin complex proteins shield telomeres from induction of DNA damage response to overcome end protection problem. A specialized ribonucleic protein, telomerase, maintains telomere homeostasis through repeat addition to counter intrinsic shortcomings of DNA replication that leads to gradual sequence shortening in successive mitoses. The biogenesis and recruitment of telomerase composed of telomerase reverse transcriptase (TERT) subunit and an RNA component, takes place through the intricate machinery that involves an elaborate number of molecules...
January 2017: Mutation Research
https://www.readbyqxmd.com/read/28342388/insights-into-the-molecular-and-biological-features-of-the-dutpase-related-gene-of-bovine-immunodeficiency-virus
#12
Yulia Podolny, Eytan Herzig, Amnon Hizi
This study was stimulated by our previous research of the dUTPase-related protein from bovine immunodeficiency virus (BIV) (Voronin et al., 2014). Despite the lack of detectable enzymatic BIV dUTPase activity (both of the recombinant protein and in virions), mutating the dUTPase gene was deleterious to viral production. However, cDNA synthesis and integration were apparently unaffected. Consequently, we have studied here two important issues. First, we showed that in cDNA produced by the dUTPase-mutated virions, the incidence of mutations was not higher than that found in wild-type BIV-infected cells...
March 22, 2017: Virology
https://www.readbyqxmd.com/read/28342223/ritonavir-and-ixazomib-kill-bladder-cancer-cells-by-causing-ubiquitinated-protein-accumulation
#13
Akinori Sato, Takako Asano, Kazuki Okubo, Makoto Isono, Tomohiko Asano
There is no curative treatment for advanced bladder cancer. Causing ubiquitinated protein accumulation and endoplasmic reticulum (ER) stress is a novel approach to cancer treatment. The human immunodeficiency virus protease inhibitor ritonavir has been reported to suppress heat shock protein 90 and increase the amount of unfolded proteins in the cell. If the proteasome functions normally, however, they are rapidly degraded. We postulated that the novel proteasome inhibitor ixazomib combined with ritonavir would kill bladder cancer cells effectively by inhibiting degradation of these unfolded proteins and thereby causing ubiquitinated proteins to accumulate...
March 25, 2017: Cancer Science
https://www.readbyqxmd.com/read/28341680/phar-a-negative-regulatory-protein-of-phap-modulates-the-colonization-of-burkholderia-gut-symbiont-in-the-midgut-of-the-host-insect-riptortus-pedestris
#14
Seong Han Jang, Ho Am Jang, Jun Beom Lee, Jong Uk Kim, Seung Ah Lee, Kyoung-Eun Park, Byung Hyun Kim, Yong Hun Jo, Bok Luel Lee
Five genes encoding PhaP family proteins and one phaR gene have been identified in the genome of Burkholderia RPE75. PhaP proteins function as the surface proteins of polyhydroxyalkanoate (PHA) granules, and PhaR protein acts as a negative regulator of PhaP biosynthesis. Recently, we characterized one phaP gene to understand the molecular cross-talk between Riptortus insects and Burkholderia gut symbionts. In this study, we constructed four other phaP gene-depleted mutants (ΔphaP1, ΔphaP2, ΔphaP3, ΔphaP4), one phaR gene-depleted mutant (ΔphaR) and a phaR-complemented mutant (ΔphaR/phaR)...
March 24, 2017: Applied and Environmental Microbiology
https://www.readbyqxmd.com/read/28341635/sept7b-is-required-for-the-subcellular-organization-of-cardiomyocytes-and-cardiac-function-in-zebrafish
#15
Surjya Narayan Dash, Suneeta Narumanchi, Jere Paavola, Sanni Perttunen, Hong Wang, Päivi Lakkisto, Ilkka Tikkanen, Sanna Lehtonen
Myofibrils made up of actin and myosin and associated proteins generate the contractile force in muscle and consequently, mutations in these proteins may lead to heart failure. Septins are a conserved family of small GTPases that associate with actin filaments, microtubules and cellular membranes. Despite the importance of septins in cytoskeleton organization, their role in cardiomyocyte organization and function is poorly characterized. Here we show that septin 7 is expressed in both embryonic and adult zebrafish heart, and elucidate the physiological significance of sept7b, the zebrafish ortholog of human septin 7, in the heart in embryonic and larval zebrafish...
March 24, 2017: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/28341549/a-quantitative-method-for-screening-and-identifying-molecular-targets-for-nanomedicine
#16
Peng Guo, Jiang Yang, Diane R Bielenberg, Deborah Dillon, David Zurakowski, Marsha A Moses, Debra T Auguste
Identifying a molecular target is essential for tumor-targeted nanomedicine. Current cancer nanomedicines commonly suffer from poor tumor specificity, "off-target" toxicity, and limited clinical efficacy. Here, we report a method to screen and identify new molecular targets for tumor-targeted nanomedicine based on a quantitative analysis. In our proof-of-principle study, we used comparative flow cytometric screening to identify ICAM-1 as a potential target for metastatic melanoma (MM). We further evaluated ICAM-1 as a MM targeting moiety by characterizing its (1) tumor specificity, (2) expression level, (3) cellular internalization, (4) therapeutic function, and (5) potential clinical impact...
March 21, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28341248/abnormal-lipid-lipoprotein-metabolism-and-high-plasma-testosterone-levels-in-male-but-not-female-aromatase-knockout-mice
#17
Akiko Amano, Yoshitaka Kondo, Yoshihiro Noda, Mitsuhiro Ohta, Noriaki Kawanishi, Shuichi Machida, Kazuteru Mitsuhashi, Takafumi Senmaru, Michiaki Fukui, Osamu Takaoka, Taisuke Mori, Jo Kitawaki, Masafumi Ono, Toshiji Saibara, Hiroshi Obayashi, Akihito Ishigami
Sex steroid hormones, such as estrogen and testosterone, are believed to play important roles in lipid metabolism. To elucidate the effects of estrogen depletion on lipid metabolism in male and female mice, we used aromatase-knockout (ArKO) mice, in which Cyp19 gene disruption prevented estrogen synthesis in vivo. These mice were divided into the following 4 groups: male and female ArKO mice and male and female wild-type (WT) mice. These mice were fed a normal-fat diet (13.6% fat) ad libitum. At 159 days after birth, the mice were tested for liver and plasma lipid content and hepatic hormone receptor- and lipid/lipoprotein metabolism-related gene expression...
March 21, 2017: Archives of Biochemistry and Biophysics
https://www.readbyqxmd.com/read/28341244/imperatorin-suppresses-proliferation-and-angiogenesis-of-human-colon-cancer-cell-by-targeting-hif-1%C3%AE-via-the-mtor-p70s6k-4e-bp1-and-mapk-pathways
#18
Chunliu Mi, Juan Ma, Ke Si Wang, Hong Xiang Zuo, Zhe Wang, Ming Yue Li, Lian Xun Piao, Guang Hua Xu, Xuezheng Li, Zhe Shan Quan, Xuejun Jin
ETHNOPHARMACOLOGICAL RELEVANCE: Angelica dahurica is a commonly used traditional Chinese medicine to treat migraine headache, toothache and cancer. Imperatorin is an active natural furocoumarin component originating from Angelica dahurica and has been shown to exhibit multiple bioeffector functions, including anti-cancer activity. However, the mechanism by which imperatorin inhibits tumor growth is not fully understood. AIM OF THE STUDY: The aim of this study was to investigate the effectiveness of imperatorin as a treatment of cancer and to identify the underlying mechanisms of its anticancer activity...
March 21, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/28341143/corrigendum-to-multiple-inhibitory-factor-removal-from-an-escherichia-coli-cell-extract-improves-cell-free-protein-synthesis-j-biosci-bioeng-108-2009-30-35
#19
Eiko Seki, Natsuko Matsuda, Takanori Kigawa
No abstract text is available yet for this article.
January 2017: Journal of Bioscience and Bioengineering
https://www.readbyqxmd.com/read/28341132/stochastic-modeling-and-numerical-simulation-of-gene-regulatory-networks-with-protein-bursting
#20
Manuel Pájaro, Antonio A Alonso, Irene Otero-Muras, C Vázquez
Gene expression is inherently stochastic. Advanced single-cell microscopy techniques together with mathematical models for single gene expression led to important insights in elucidating the sources of intrinsic noise in prokaryotic and eukaryotic cells. In addition to the finite size effects due to low copy numbers, translational bursting is a dominant source of stochasticity in cell scenarios involving few short lived mRNA transcripts with high translational efficiency (as is typically the case for prokaryotes), causing protein synthesis to occur in random bursts...
March 21, 2017: Journal of Theoretical Biology
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