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https://www.readbyqxmd.com/read/28636205/progressive-scar14-with-unclear-speech-developmental-delay-tremor-and-behavioral-problems-caused-by-a-homozygous-deletion-of-the-sptbn2-pleckstrin-homology-domain
#1
Esra Yıldız Bölükbaşı, Muhammad Afzal, Sara Mumtaz, Nafees Ahmad, Sajid Malik, Aslıhan Tolun
We report on nine members of a consanguineous Pakistani family with primary presentation of intellectual disability, developmental delay, limb and gait ataxia, behavioral and speech problems, and tremor. By linkage mapping and exome sequencing we identified novel homozygous splicing variant c.6375-1G>C in SPTBN2. To date, only two other SPTBN2 mutations with recessive pattern of inheritance causing SCAR14 (spinocerebellar ataxia, autosomal recessive 14) that manifest with developmental ataxia and cognitive impairment, or cerebellar ataxia, mental retardation, and pyramidal signs have been reported...
June 21, 2017: American Journal of Medical Genetics. Part A
https://www.readbyqxmd.com/read/28636168/improved-hemodialysis-with-hemocompatible-polyethersulfone-hollow-fiber-membranes-in-vitro-performance
#2
Surendra Kumar Verma, Akshay Modi, Atul Kumar Singh, Rohit Teotia, Jayesh Bellare
We show that addition of nanozeolite (NZ) and vitamin E D-α-Tocopherol polyethylene glycol succinate (TPGS or T) considerably improves the performance of polyethersulfone (PES or P) hollow fiber membrane (HFM) for hemodialysis. Nanocomposite HFMs were manufactured using PES as a polymer, TPGS as an additive and NZ as a filler to give a composite membrane called PT-NZ. HFMs were spun by dry-wet spinning principle based on liquid-liquid phase separation. TPGS and NZ were successfully incorporated in HFMs, as confirmed by EDX elemental mapping...
June 21, 2017: Journal of Biomedical Materials Research. Part B, Applied Biomaterials
https://www.readbyqxmd.com/read/28636028/supramolecular-functional-assemblies-dynamic-membrane-transporters-and-peptide-nanotubular-composites
#3
Alberto Fuertes, Marisa Juanes, Juan R Granja, Javier Montenegro
The fabrication of functional molecular devices constitutes one of the most important current challenges for chemical sciences. The complex processes accomplished by living systems continuously demand the assistance of non-covalent interactions between molecular building blocks. Additionally, these building blocks (proteins, membranes, nucleotides) are also constituted by self-assembled structures. Therefore, supramolecular chemistry is the discipline required to understand the properties of the minimal self-assembled building blocks of living systems and to develop new functional smart materials...
June 21, 2017: Chemical Communications: Chem Comm
https://www.readbyqxmd.com/read/28636010/engineering-multi-functional-bacterial-outer-membrane-vesicles-as-modular-nanodevices-for-biosensing-and-bioimaging
#4
Qi Chen, Sharon Rozovsky, Wilfred Chen
Outer membrane vesicles (OMVs) are proteoliposomes derived from the outer membrane and periplasmic space of many Gram-negative bacteria including E. coli as part of their natural growth cycle. Inspired by the natural ability of E. coli to sort proteins to both the exterior and interior of OMVs, we reported here a one-pot synthesis approach to engineer multi-functionalized OMV-based sensors for both antigen binding and signal generation. SlyB, a native lipoprotein, was used a fusion partner to package nanoluciferase (Nluc) within OMVs, while a previously developed INP-Scaf3 surface scaffold was fused to the Z-domain for antibody recruiting...
June 21, 2017: Chemical Communications: Chem Comm
https://www.readbyqxmd.com/read/28635961/hypoxia-induced-mobilization-of-nhe6-to-the-plasma-membrane-triggers-endosome-hyperacidification-and-chemoresistance
#5
Fabrice Lucien, Pierre-Paul Pelletier, Roxane R Lavoie, Jean-Michel Lacroix, Sébastien Roy, Jean-Luc Parent, Dominique Arsenault, Kelly Harper, Claire M Dubois
The pH-dependent partitioning of chemotherapeutic drugs is a fundamental yet understudied drug distribution mechanism that may underlie the low success rates of current approaches to counter multidrug resistance (MDR). This mechanism is influenced by the hypoxic tumour microenvironment and results in selective trapping of weakly basic drugs into acidified compartments such as the extracellular environment. Here we report that hypoxia not only leads to acidification of the tumour microenvironment but also induces endosome hyperacidification...
June 21, 2017: Nature Communications
https://www.readbyqxmd.com/read/28635952/yunis-var%C3%A3-n-syndrome-caused-by-biallelic-vac14-mutations
#6
Matthew A Lines, Yoko Ito, Kristin D Kernohan, Wendy Mears, Julie Hurteau-Miller, Sunita Venkateswaran, Leanne Ward, Karine Khatchadourian, Jeff McClintock, Priya Bhola, Philippe M Campeau, Kym M Boycott, Jean Michaud, André Bp van Kuilenburg, Sacha Ferdinandusse, David A Dyment
Yunis-Varón syndrome (YVS) is an autosomal recessive disorder comprising skeletal anomalies, dysmorphism, global developmental delay and intracytoplasmic vacuolation in brain and other tissues. All hitherto-reported pathogenic variants affect FIG4, a lipid phosphatase involved in phosphatidylinositol (3,5)-bisphosphate [PtdIns(3,5)P2] metabolism. FIG4 interacts with PIKfyve, a lipid kinase, via the adapter protein VAC14; all subunits of the resulting complex are essential for PtdIns(3,5)P2 synthesis in the endolysosomal membrane compartment...
June 21, 2017: European Journal of Human Genetics: EJHG
https://www.readbyqxmd.com/read/28635671/rab33b-controls-hepatitis-b-virus-assembly-by-regulating-core-membrane-association-and-nucleocapsid-processing
#7
Christina Bartusch, Tatjana Döring, Reinhild Prange
Many viruses take advantage of cellular trafficking machineries to assemble and release new infectious particles. Using RNA interference (RNAi), we demonstrate that the Golgi/autophagosome-associated Rab33B is required for hepatitis B virus (HBV) propagation in hepatoma cell lines. While Rab33B is dispensable for the secretion of HBV subviral envelope particles, its knockdown reduced the virus yield to 20% and inhibited nucleocapsid (NC) formation and/or NC trafficking. The overexpression of a GDP-restricted Rab33B mutant phenocopied the effect of deficit Rab33B, indicating that Rab33B-specific effector proteins may be involved...
June 21, 2017: Viruses
https://www.readbyqxmd.com/read/28635657/selection-of-nucleic-acid-aptamers-targeting-tumor-cell-surface-protein-biomarkers
#8
REVIEW
Marie-Cécile Mercier, Monique Dontenwill, Laurence Choulier
Aptamers are nucleic acids referred to as chemical antibodies as they bind to their specific targets with high affinity and selectivity. They are selected via an iterative process known as 'selective evolution of ligands by exponential enrichment' (SELEX). Aptamers have been developed against numerous cancer targets and among them, many tumor cell-membrane protein biomarkers. The identification of aptamers targeting cell-surface proteins has mainly been performed by two different strategies: protein- and cell-based SELEX, when the targets used for selection were proteins and cells, respectively...
June 21, 2017: Cancers
https://www.readbyqxmd.com/read/28635493/the-structure-of-lamin-filaments-in-somatic-cells-as-revealed-by-cryo-electron-tomography
#9
Y Turgay, O Medalia
Metazoan nuclei are equipped with nuclear lamina - a thin layer of intermediate filaments (IFs) mostly built of nuclear lamins facing the inner nuclear membrane (INM). The nuclear lamina serves as an interaction hub for INM-proteins, soluble nuclear factors and DNA. It confers structural and mechanical stability to the nucleus, transduces mechanical forces and biochemical signals across the nuclear envelope (NE) and regulates the organization of chromatin. By utilizing cryo-electron tomography (cryo-ET), we recently provided an unprecedented view into the 3D organization of lamin filaments within the lamina meshwork in mammalian somatic cells...
June 21, 2017: Nucleus
https://www.readbyqxmd.com/read/28634572/a-helicobacter-pylori-homolog-of-eukaryotic-flotillin-is-involved-in-cholesterol-accumulation-epithelial-cell-responses-and-host-colonization
#10
Melanie L Hutton, Kimberley D'Costa, Amanda E Rossiter, Lin Wang, Lorinda Turner, David L Steer, Seth L Masters, Ben A Croker, Maria Kaparakis-Liaskos, Richard L Ferrero
The human pathogen Helicobacter pylori acquires cholesterol from membrane raft domains in eukaryotic cells, commonly known as "lipid rafts." Incorporation of this cholesterol into the H. pylori cell membrane allows the bacterium to avoid clearance by the host immune system and to resist the effects of antibiotics and antimicrobial peptides. The presence of cholesterol in H. pylori bacteria suggested that this pathogen may have cholesterol-enriched domains within its membrane. Consistent with this suggestion, we identified a hypothetical H...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/28634536/telavancin-a-novel-semisynthetic-lipoglycopeptide-agent-to-counter-the-challenge-of-resistant-gram-positive-pathogens
#11
REVIEW
Biswadeep Das, Chayna Sarkar, Debasmita Das, Amit Gupta, Arnav Kalra, Shubham Sahni
Telavancin (TD-6424), a semisynthetic lipoglycopeptide vancomycin-derivative, is a novel antimicrobial agent developed by Theravance for overcoming resistant Gram-positive bacterial infections, specifically methicillin-resistant Staphylococcus aureus (MRSA). The US Food and Drug Administration (USFDA) had approved telavancin in 2009 for the treatment of complicated skin and skin structure infections (cSSSIs) caused by Gram-positive bacteria, including MRSA (S. aureus, Streptococcus agalactiae, Streptococcus pyogenes, Streptococcus anginosus group, or Enterococcus faecalis)...
March 2017: Therapeutic Advances in Infectious Disease
https://www.readbyqxmd.com/read/28634471/a-chitin-binding-protein-purified-from-moringa-oleifera-seeds-presents-anticandidal-activity-by-increasing-cell-membrane-permeability-and-reactive-oxygen-species-production
#12
João X S Neto, Mirella L Pereira, Jose T A Oliveira, Lady C B Rocha-Bezerra, Tiago D P Lopes, Helen P S Costa, Daniele O B Sousa, Bruno A M Rocha, Thalles B Grangeiro, José E C Freire, Ana Cristina O Monteiro-Moreira, Marina D P Lobo, Raimunda S N Brilhante, Ilka M Vasconcelos
Candida species are opportunistic pathogens that infect immunocompromised and/or immunosuppressed patients, particularly in hospital facilities, that besides representing a significant threat to health increase the risk of mortality. Apart from echinocandins and triazoles, which are well tolerated, most of the antifungal drugs used for candidiasis treatment can cause side effects and lead to the development of resistant strains. A promising alternative to the conventional treatments is the use of plant proteins...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28634441/roles-of-pannexin-1-channels-in-inflammatory-response-through-the-tlrs-nf-kappa-b-signaling-pathway-following-experimental-subarachnoid-hemorrhage-in-rats
#13
Ling-Yun Wu, Zhen-Nan Ye, Chen-Hui Zhou, Chun-Xi Wang, Guang-Bin Xie, Xiang-Sheng Zhang, Yong-Yue Gao, Zi-Huan Zhang, Meng-Liang Zhou, Zong Zhuang, Jing-Peng Liu, Chun-Hua Hang, Ji-Xin Shi
Background: Accumulating evidence suggests that neuroinflammation plays a critical role in early brain injury after subarachnoid hemorrhage (SAH). Pannexin-1 channels, as a member of gap junction proteins located on the plasma membrane, releases ATP, ions, second messengers, neurotransmitters, and molecules up to 1 kD into the extracellular space, when activated. Previous studies identified that the opening of Pannexin-1 channels is essential for cellular migration, apoptosis and especially inflammation, but its effects on inflammatory response in SAH model have not been explored yet...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28634440/cysteines-as-redox-molecular-switches-and-targets-of-disease
#14
REVIEW
Annamaria Fra, Edgar D Yoboue, Roberto Sitia
Thiol groups can undergo numerous modifications, making cysteine a unique molecular switch. Cysteine plays structural and regulatory roles as part of proteins or glutathione, contributing to maintain redox homeostasis and regulate signaling within and amongst cells. Not surprisingly therefore, cysteines are associated with many hereditary and acquired diseases. Mutations in the primary protein sequence (gain or loss of a cysteine) are most frequent in membrane and secretory proteins, correlating with the key roles of disulfide bonds...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28634303/structural-characterization-of-the-rabphilin-3a-snap25-interaction
#15
Cristina Ferrer-Orta, María Dolores Pérez-Sánchez, Teresa Coronado-Parra, Cristina Silva, David López-Martínez, Jesús Baltanás-Copado, Juan Carmelo Gómez-Fernández, Senena Corbalán-García, Núria Verdaguer
Membrane fusion is essential in a myriad of eukaryotic cell biological processes, including the synaptic transmission. Rabphilin-3A is a membrane trafficking protein involved in the calcium-dependent regulation of secretory vesicle exocytosis in neurons and neuroendocrine cells, but the underlying mechanism remains poorly understood. Here, we report the crystal structures and biochemical analyses of Rabphilin-3A C2B-SNAP25 and C2B-phosphatidylinositol 4,5-bisphosphate (PIP2) complexes, revealing how Rabphilin-3A C2 domains operate in cooperation with PIP2/Ca(2+) and SNAP25 to bind the plasma membrane, adopting a conformation compatible to interact with the complete SNARE complex...
June 20, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28634272/the-secreted-msp-domain-of-c-elegans-vapb-homolog-vpr-1-patterns-the-adult-striated-muscle-mitochondrial-reticulum-via-smn-1
#16
Jessica Schultz, Se-Jin Lee, Tim Cole, Hieu D Hoang, Jack Vibbert, Pauline A Cottee, Michael A Miller, Sung Min Han
The major sperm protein domain (MSPd) has an extracellular signaling function implicated in amyotrophic lateral sclerosis. Secreted MSPds derived from the C. elegans VAPB homolog VPR-1 promote mitochondrial localization to actin-rich I-bands in body wall muscle. Here we show that the nervous system and germ line are key MSPd secretion tissues. MSPd signals are transduced through the CLR-1 Lar-like tyrosine phosphatase receptor. We show that CLR-1 is expressed throughout the muscle plasma membrane, where it is accessible to MSPd within the pseudocoelomic fluid...
June 15, 2017: Development
https://www.readbyqxmd.com/read/28634262/rassf4-regulator-of-plasma-membrane-pi-4-5-p2
#17
Eamonn J Dickson
Phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) is a negatively charged phospholipid that plays a major role in recruiting and regulating proteins at the plasma membrane-cytosol interface. In this issue, Chen et al. (2017. J. Cell Biol. https://doi.org/10.1083/jcb.201606047) demonstrate that RAS association domain family 4 (RASSF4) positively influences PI(4,5)P2 synthesis through ARF6-dependent regulation of PIP5K.
June 20, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28634242/type-ii-secretion-substrates-of-legionella-pneumophila-translocate-out-of-the-pathogen-occupied-vacuole-via-a-semipermeable-membrane
#18
Hilary K Truchan, Harry D Christman, Richard C White, Nakisha S Rutledge, Nicholas P Cianciotto
Legionella pneumophila replicates in macrophages in a host-derived phagosome, termed the Legionella-containing vacuole (LCV). While the translocation of type IV secretion (T4S) effectors into the macrophage cytosol is well established, the location of type II secretion (T2S) substrates in the infected host cell is unknown. Here, we show that the T2S substrate ProA, a metalloprotease, translocates into the cytosol of human macrophages, where it associates with the LCV membrane (LCVM). Translocation is detected as early as 10 h postinoculation (p...
June 20, 2017: MBio
https://www.readbyqxmd.com/read/28634234/the-thioreduction-component-ccmg-confers-efficiency-and-the-heme-ligation-component-ccmh-ensures-stereo-specificity-during-cytochrome-c-maturation
#19
Andreia F Verisssimo, Bahia Khalfaoui-Hassani, Josephine Hwang, Stefan Steimle, Nur Selamoglu, Carsten Sanders, Camilo Khatchikian, Fevzi Daldal
In many Gram-negative bacteria, including Rhodobacter capsulatus, cytochrome c maturation (Ccm) is carried out by a membrane-integral machinery composed of nine proteins (CcmA to I). During this process, the periplasmic thiol-disulfide oxidoreductase DsbA is thought to catalyze the formation of a disulfide bond between the Cys residues at the apocytochrome c heme binding site (CXXCH). Subsequently, a Ccm-specific thioreductive pathway involving CcmG and CcmH reduces this disulfide bond to allow covalent heme ligation...
June 20, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28634138/intracellular-and-transdermal-protein-delivery-mediated-by-non-covalent-interactions-with-a-synthetic-guanidine-rich-molecular-carrier
#20
Jungkyun Im, Sanket Das, Dongjun Jeong, Chang-Jin Kim, Hyun-Suk Lim, Ki Hean Kim, Sung-Kee Chung
The impermeability of the cell plasma membrane is one of the major barriers for protein transduction into mammalian cells, and it also limits the use of proteins as therapeutic agents. Protein transduction has usually been achieved based on certain invasive processes or cell penetrating peptides (CPP). Herein we report our study in which a synthetic guanidine-rich molecular carrier is used as a delivery vector for intracellular and transdermal delivery of proteins. First a sorbitol-based molecular carrier having 8 guanidine units (Sor-G8) was synthesized, and then was simply mixed with a cargo protein of varying sizes to form the non-covalent complex of carrier-cargo proteins...
June 17, 2017: International Journal of Pharmaceutics
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