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https://www.readbyqxmd.com/read/29223072/alteration-of-autophagy-related-proteins-in-peripheral-blood-mononuclear-cells-of-patients-with-parkinson-s-disease
#1
Yasuo Miki, Shuji Shimoyama, Tomoya Kon, Tatsuya Ueno, Ryo Hayakari, Kunikazu Tanji, Tomoh Matsumiya, Eiki Tsushima, Fumiaki Mori, Koichi Wakabayashi, Masahiko Tomiyama
Previous postmortem studies demonstrated dysregulation of autophagy in patients with Parkinson's disease (PD). To clarify whether this alteration reflects a fundamental aspect of PD or represents the final stage of autophagy dysregulation resulting from a long neurodegenerative process, we focused on basal autophagy in peripheral blood mononuclear cells (PBMCs) of PD patients (n = 35) and controls (n = 23). The whole-transcriptome assay revealed downregulation of mRNAs for 6 core regulators of autophagy (UNC-51-like kinase [ULK] 3, autophagy-related [Atg] 2A, Atg4B, Atg5, Atg16L1, and histone deacetylase 6)...
November 21, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/29222970/relaxation-of-structural-constraints-during-amicyanin-unfolding
#2
John J Kozak, Harry B Gray, Roberto A Garza-López
We study the thermal unfolding of amicyanin by quantifying the resiliency of the native state to structural perturbations. Three signatures characterizing stages of unfolding are identified. The first signature, lateral extension of the polypeptide chain, is calculated directly from the reported crystallographic data. Two other signatures, the radial displacement of each residue from Cu(II) and the angular spread in the chain as the protein unfolds, are calculated using crystallographic data in concert with a geometrical model we introduced previously (J...
November 22, 2017: Journal of Inorganic Biochemistry
https://www.readbyqxmd.com/read/29222010/a-novel-nr2f2-loss-of-function-mutation-predisposes-to-congenital-heart-defect
#3
Xiao-Hui Qiao, Qian Wang, Juan Wang, Xing-Yuan Liu, Ying-Jia Xu, Ri-Tai Huang, Song Xue, Yan-Jie Li, Min Zhang, Xin-Kai Qu, Ruo-Gu Li, Xing-Biao Qiu, Yi-Qing Yang
Congenital heart defect (CHD) is the most common type of birth defect in humans and a leading cause of infant morbidity and mortality. Previous studies have demonstrated that genetic defects play a pivotal role in the pathogenesis of CHD. However, the genetic basis of CHD remains poorly understood due to substantial genetic heterogeneity. In this study, the coding exons and splicing boundaries of the NR2F2 gene, which encodes a pleiotropic transcription factor required for normal cardiovascular development, were sequenced in 168 unrelated patients with CHD, and a novel mutation (c...
December 5, 2017: European Journal of Medical Genetics
https://www.readbyqxmd.com/read/29221909/maintaining-the-active-zone-demand-supply-and-disposal-of-core-active-zone-proteins
#4
REVIEW
Noam E Ziv
Chemical synapses are sites of cell-cell contact specialized for transmission of signals between neurons and their respective targets. Neurotransmission occurs through the secretion of neurotransmitters at specialized presynaptic membrane regions known as Active Zones (AZs). AZ composition and function are now characterized quite well. Much less is known, however, on the manners by which these unique specializations are maintained for weeks, months, and presumably years. Here we focus on core AZ components that make up the Cytoskeleton associated with the AZ (CAZ) - their lifetimes, their supply and their disposal...
December 5, 2017: Neuroscience Research
https://www.readbyqxmd.com/read/29221896/correlative-imaging-reveals-physiochemical-heterogeneity-of-microcalcifications-in-human-breast-carcinomas
#5
Jennie A M R Kunitake, Siyoung Choi, Kayla X Nguyen, Meredith M Lee, Frank He, Daniel Sudilovsky, Patrick G Morris, Maxine S Jochelson, Clifford A Hudis, David A Muller, Peter Fratzl, Claudia Fischbach, Admir Masic, Lara A Estroff
Microcalcifications (MCs) are routinely used to detect breast cancer in mammography. Little is known, however, about their materials properties and associated organic matrix, or their correlation to breast cancer prognosis. We combine histopathology, Raman microscopy, and electron microscopy to image MCs within snap-frozen human breast tissue and generate micron-scale resolution correlative maps of crystalline phase, trace metals, particle morphology, and organic matrix chemical signatures within high grade ductal carcinoma in situ (DCIS) and invasive cancer...
December 5, 2017: Journal of Structural Biology
https://www.readbyqxmd.com/read/29220510/ciliopathy-associated-mutations-of-ift122-impair-ciliary-protein-trafficking-but-not-ciliogenesis
#6
Mariko Takahara, Yohei Katoh, Kentaro Nakamura, Tomoaki Hirano, Maho Sugawa, Yuta Tsurumi, Kazuhisa Nakayama
The intraflagellar transport (IFT) machinery containing the IFT-A and IFT-B complexes mediates ciliary protein trafficking. Mutations in the genes encoding the six subunits of the IFT-A complex (IFT43, IFT121, IFT122, IFT139, IFT140, and IFT144) are known to cause skeletal ciliopathies, including cranioectodermal dysplasia (CED). As the IFT122 subunit connects the core and peripheral subcomplexes of the IFT-A complex, it is expected to play a pivotal role in the complex. Indeed, we here showed that knockout (KO) of the IFT122 gene in hTERT-RPE1 cells using the CRISPR/Cas9 system led to a severe ciliogenesis defect, whereas KO of other IFT-A genes had minor effects on ciliogenesis but impaired ciliary protein trafficking...
December 6, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/29218636/incorporation-of-second-coordination-sphere-d-amino-acids-alters-cd-ii-geometries-in-designed-thiolate-rich-proteins
#7
Leela Ruckthong, Aniruddha Deb, Lars Hemmingsen, James E Penner-Hahn, Vincent L Pecoraro
We use a de Novo protein design strategy to demonstrate that the second coordination sphere of a metal site plays a key role in controlling coordination geometries of Cd(II)-tris-thiolate complexes. Specifically, we show that alteration of chirality within the core hydrophobic packing region of a three-stranded coiled coil (3SCC) can control the coordination number of Cd(II) by limiting steric encumbrance to the metal center. Within a specific class of 3SCCs [Ac-G-(LKALEEK) n -G-NH2], where n = 4 is TRI and n = 5 is GRAND, one L-Leu may be substituted by L-Cys to generate a planar tris-thiolate array capable of metal binding...
December 7, 2017: Journal of Biological Inorganic Chemistry: JBIC
https://www.readbyqxmd.com/read/29218250/evaluation-of-the-role-of-downregulation-of-snf5-ini1-core-subunit-of-swi-snf-complex-in-clear-cell-renal-cell-carcinoma-development
#8
Elzbieta Sarnowska, Michal Szymanski, Nataliia Rusetska, Marcin Ligaj, Iga Jancewicz, Pawel Cwiek, Marta Skrodzka, Marcin Leszczynski, Joanna Szarkowska, Alicja Chrzan, Malgorzata Stachowiak, Jaroslaw Steciuk, Anna Maassen, Lech Galek, Tomasz Demkow, Janusz A Siedlecki, Tomasz J Sarnowski
Clear cell renal cell carcinoma (ccRCC) is characterized by stabilization of hypoxia-inducible factor (HIF1), and mutations in von Hippel-Lindau (VHL) gene. Additionally, in about 40% of ccRCC cases the mutation in PBRM1 (POLYBROMO1) gene coding for a non-core subunit of SWI/SNF chromatin remodeling complex was found suggesting potential impairment of this complex function in ccRCC. In this study we assessed the extent to which the core SWI/SNF complex subunit - INI1 (hSNF5/SMARCB1) is affected in ccRCC and whether it has any consequences on the development of this type of cancer...
2017: American Journal of Cancer Research
https://www.readbyqxmd.com/read/29218011/pharmacogenetic-variation-in-over-100-genes-in-patients-receiving-acenocumarol
#9
Vanessa Gonzalez-Covarrubias, Javier Urena-Carrion, Beatriz Villegas-Torres, J Eduardo Cossío-Aranda, Sergio Trevethan-Cravioto, Raul Izaguirre-Avila, O Javier Fiscal-López, Xavier Soberon
Coumarins are widely prescribed worldwide, and in Mexico acenocumarol is the preferred form. It is well known that despite its efficacy, coumarins show a high variability for dose requirements. We investigated the pharmacogenetic variation of 110 genes in patients receiving acenocumarol using a targeted NGS approach. We report relevant population differentiation for variants on CYP2C8, CYP2C19, CYP4F11, CYP4F2, PROS, and GGCX, VKORC1, CYP2C18, NQO1. A higher proportion of novel-to-known variants for 10 genes was identified on 41 core pharmacogenomics genes related to the PK (29), PD (3), of coumarins, and coagulation proteins (9) including, CYP1A1, CYP3A4, CYP3A5, and F8, and a low proportion of novel-to-known variants on CYP2E1, VKORC1, and SULT1A1/2...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29216535/nanoantagonists-with-nanophase-segregated-surfaces-for-improved-cancer-immunotherapy
#10
Yang Ma, Sheng-Lin Qiao, Yi Wang, Yao-Xin Lin, Hong-Wei An, Xiao-Chun Wu, Lei Wang, Hao Wang
The blockade of PD-1/PD-L1 interaction by peptide antagonists can unleash and enhance pre-existing anti-cancer immune responses of T cells to eradicate cancer cells. However, low proteolytic stability is the "Achilles' Heel" of peptides. Here, we first report a nanoantagonist with a physiological temperature sensitive nanophase-segregated surface that exhibits significantly enhanced blood circulation, peptide stability and PD-L1 immune checkpoint blockade efficacy. Thermosensitive polymers with different phase transition temperatures (Tt) are used to form the nanophase-segregated surface on an Au nanorod core...
December 1, 2017: Biomaterials
https://www.readbyqxmd.com/read/29215008/roles-of-two-types-of-heparan-sulfate-clusters-in-wnt-distribution-and-signaling-in-xenopus
#11
Yusuke Mii, Takayoshi Yamamoto, Ritsuko Takada, Shuji Mizumoto, Makoto Matsuyama, Shuhei Yamada, Shinji Takada, Masanori Taira
Wnt proteins direct embryonic patterning, but the regulatory basis of their distribution and signal reception remain unclear. Here, we show that endogenous Wnt8 protein is distributed in a graded manner in Xenopus embryo and accumulated on the cell surface in a punctate manner in association with "N-sulfo-rich heparan sulfate (HS)," not with "N-acetyl-rich HS". These two types of HS are differentially clustered by attaching to different glypicans as core proteins. N-sulfo-rich HS is frequently internalized and associated with the signaling vesicle, known as the Frizzled/Wnt/LRP6 signalosome, in the presence of Wnt8...
December 7, 2017: Nature Communications
https://www.readbyqxmd.com/read/29214735/the-mechanism-study-of-mir-125b-in-occurrence-and-progression-of-multiple-myeloma
#12
Da Gao, Zhen Xiao, Hui-Ping Li, Dong-Hai Han, Ya-Peng Zhang
Although many efforts have contributed to improve our knowledge of molecular pathogenesis about multiple myeloma (MM), the role and significance of microRNAs and long noncoding RNAs in MM cells, along with the core mechanism remains virtually absent. The mRNA levels of miR-125b and MALAT1 in MM cell lines were detected by qRT-PCR. The influence of Lenti-Sh-miR-125b on cell viability and the Notch-1 pathway-related proteins were assessed by MTT method and western blot, respectively. We also investigated the regulation effect between MALAT1 and Notch1 pathway...
December 7, 2017: Cancer Medicine
https://www.readbyqxmd.com/read/29214470/clinical-and-anti-aging-effect-of-mud-bathing-therapy-for-patients-with-fibromyalgia
#13
Toyoki Maeda, Yoshihiro Kudo, Takahiko Horiuchi, Naoki Makino
Spa bathing is known as a medical treatment for certain diseases causing chronic pains. Spa water contains mineral components which lower the specific heat of the water, resulting in a higher efficiency to warm body-core temperature. This phenomenon yields pain-relieving effect for rheumatoid arthritis, low back pain, sciatic neuralgia, fibromyalgia, etc. Here we introduce medical and biological effects of mud-spa-bathing therapy for fibromyalgia other than pain relief, the changes of blood examination data, and the telomere length of circulating leukocytes...
December 6, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/29214311/fingolimod-suppresses-a-cascade-of-core-vicious-cycle-in-dry-eye-nod-mouse-model-involvement-of-sphingosine-1-phosphate-receptors-in-infiltrating-leukocytes
#14
Weibao Xiao, Shuhao Fu, Kang Xu, Ronghua Feng, Fei Sun, Wen Ye
Purpose: The purpose of this study was to evaluate the inhibitory mechanism of fingolimod and the involvement of sphingosine-1-phosphate receptors (S1PRs) and cytokines-matrix metalloproteinases (MMPs)/MAP kinases (MAPKs) signaling in a dry eye disease (DED) mouse model. Methods: Sixty-four male NOD mice (DED model) and 16 age-matched BALB/c mice were used. In a preliminary experiment, 16 NOD mice were randomly divided into a positive control group and fingolimod-treated groups, with 8 BALB/c mice serving as wild-type control...
December 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/29214235/kinetics-and-thermodynamics-of-dbpa-protein-s-c-terminal-domain-interaction-with-rna
#15
Aliana López de Victoria, Anthony F T Moore, Apostolos G Gittis, Eda Koculi
DbpA is an Escherichia coli DEAD-box RNA helicase implicated in RNA structural isomerization in the peptide bond formation site. In addition to the RecA-like catalytic core conserved in all of the members of DEAD-box family, DbpA contains a structured C-terminal domain, which is responsible for anchoring DbpA to hairpin 92 of 23S ribosomal RNA during the ribosome assembly process. Here, surface plasmon resonance was used to determine the equilibrium dissociation constant and the microscopic rate constants of the DbpA C-terminal domain association and dissociation to a fragment of 23S ribosomal RNA containing hairpin 92...
November 30, 2017: ACS Omega
https://www.readbyqxmd.com/read/29213150/strategies-to-increase-the-thermal-stability-of-truly-biomimetic-hydrogels-combining-hydrophobicity-and-directed-hydrogen-bonding
#16
Hongbo Yuan, Jialiang Xu, Eliane P van Dam, Giulia Giubertoni, Yves L A Rezus, Roel Hammink, Huib J Bakker, Yong Zhan, Alan E Rowan, Chengfen Xing, Paul H J Kouwer
Enhancing the thermal stability of proteins is an important task for protein engineering. There are several ways to increase the thermal stability of proteins in biology, such as greater hydrophobic interactions, increased helical content, decreased occurrence of thermolabile residues, or stable hydrogen bonds. Here, we describe a well-defined polymer based on β-helical polyisocyanotripeptides (TriPIC) that uses biological approaches, including hydrogen bonding and hydrophobic interactions for its exceptional thermal stability in aqueous solutions...
November 28, 2017: Macromolecules
https://www.readbyqxmd.com/read/29212933/characterization-of-an-influenza-virus-pseudotyped-with-ebolavirus-glycoprotein
#17
Julie Xiao, Pramila Rijal, Lisa Schimanski, Arun Kumar Tharkeshwar, Edward Wright, Wim Annaert, Alain Townsend
We have produced a new Ebola virus pseudotype: E-S-FLU, which can be handled in biosafety level-1/2 containment for laboratory analysis. E-S-FLU is a single cycle influenza virus coated with Ebolavirus glycoprotein, and it encodes enhanced green fluorescence protein as a reporter that replaces the influenza haemagglutinin. MDCK-SIAT1 cells were transduced to express Ebolavirus glycoprotein as a stable transmembrane protein for E-S-FLU production. Infection of cells by E-S-FLU was dependent on Niemann-Pick C1 protein, which is the well-characterized receptor for Ebola virus entry at the late endosome/lysosome membrane...
December 6, 2017: Journal of Virology
https://www.readbyqxmd.com/read/29212814/structural-basis-for-assembly-of-the-cbf3-kinetochore-complex
#18
Vera Leber, Andrea Nans, Martin R Singleton
Eukaryotic chromosomes contain a specialised region known as the centromere, which forms the platform for kinetochore assembly and microtubule attachment. The centromere is distinguished by the presence of nucleosomes containing the histone H3 variant, CENP-A. In budding yeast, centromere establishment begins with the recognition of a specific DNA sequence by the CBF3 complex. This in turn facilitates CENP-ACse4 nucleosome deposition and kinetochore assembly. Here, we describe a 3.6 Å single-particle cryo-EM reconstruction of the core CBF3 complex, incorporating the sequence-specific DNA-binding protein Cep3 together with regulatory subunits Ctf13 and Skp1...
December 6, 2017: EMBO Journal
https://www.readbyqxmd.com/read/29212769/functional-and-structural-characterization-of-a-novel-malignant-hyperthermia-susceptible-variant-of-dhpr-%C3%AE-1a-subunit-cacnb1
#19
Claudio F Perez, Jose M Eltit, Jose R Lopez, Dóra Bodnár, Angela F Dulhunty, Shouvik Aditya, Marco G Casarotto
Malignant Hyperthermia (MH) susceptibility has been recently linked to a novel variant of β1a subunit of the dihydropyridine receptor (DHPR), a channel essential for Ca2+ regulation in skeletal muscle. Here we evaluate the effect of the mutant variant V156A on the structure/function of DHPR β1a subunit and assess its role on Ca2+ metabolism of cultured myotubes. Using differential scanning fluorimetry we show that mutation V156A causes a significant reduction in thermal stability of the Src homology 3 (SH3)/Guanylate Kinase (GK) core domain of β1a subunit...
December 6, 2017: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/29211845/gene-deletions-leading-to-a-reduction-in-the-number-of-cyclopentane-rings-in-sulfolobus-acidocaldarius-tetraether-lipids
#20
Ziqiang Guan, Antonia Delago, Phillip Nußbaum, Benjamin H Meyer, Sonja-Verena Albers, Jerry Eichler
The cell membrane of (hyper)thermophilic archaea, including the thermoacidophile Sulfolobus acidocaldarius, incorporate dibiphytanylglycerol tetraether lipids. The hydrophobic cores of such tetraether lipids can include up to eight cyclopentane rings. Presently, nothing is known of the biosynthesis of these rings. In the present study, a series of S. acidocaldarius mutants deleted of genes currently annotated as encoding proteins involved in sugar/polysaccharide processing were generated and their glycolipids were considered...
November 29, 2017: FEMS Microbiology Letters
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