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https://www.readbyqxmd.com/read/28088541/secretory-pathway-optimization-of-cho-producer-cells-by-co-engineering-of-the-mitosrna-1978-target-genes-cers2-and-tbc1d20
#1
Lisa A Pieper, Michaela Strotbek, Till Wenger, Martin Gamer, Monilola A Olayioye, Angelika Hausser
Chinese Hamster Ovary (CHO) cells are the most commonly used host for the production of biopharmaceuticals. Although transcription and translation engineering strategies have been employed to generate high-producer cell clones, the secretory pathway still remains a bottleneck in cellular productivity. In this study we show that ectopic expression of a human mitochondrial genome-encoded small RNA (mitosRNA-1978) in an IgG expressing CHO cell line strongly improved specific productivity by functioning in a microRNA-like fashion...
January 11, 2017: Metabolic Engineering
https://www.readbyqxmd.com/read/28077878/pla2g16-represents-a-switch-between-entry-and-clearance-of-picornaviridae
#2
Jacqueline Staring, Eleonore von Castelmur, Vincent A Blomen, Lisa G van den Hengel, Markus Brockmann, Jim Baggen, Hendrik Jan Thibaut, Joppe Nieuwenhuis, Hans Janssen, Frank J M van Kuppeveld, Anastassis Perrakis, Jan E Carette, Thijn R Brummelkamp
Picornaviruses are a leading cause of human and veterinary infections that result in various diseases, including polio and the common cold. As archetypical non-enveloped viruses, their biology has been extensively studied. Although a range of different cell-surface receptors are bound by different picornaviruses, it is unclear whether common host factors are needed for them to reach the cytoplasm. Using genome-wide haploid genetic screens, here we identify the lipid-modifying enzyme PLA2G16 (refs 8, 9, 10, 11) as a picornavirus host factor that is required for a previously unknown event in the viral life cycle...
January 11, 2017: Nature
https://www.readbyqxmd.com/read/28077646/adenovirus-modulates-toll-like-receptor-4-signaling-by-reprogramming-orp1l-vap-protein-contacts-for-cholesterol-transport-from-endosomes-to-the-endoplasmic-reticulum
#3
Nicholas L Cianciola, Stacey Chung, Danny Manor, Cathleen R Carlin
: Human adenoviruses generally cause mild self-limiting infections but can lead to serious disease and even be fatal in high-risk individuals, underscoring the importance of understanding how the virus counteracts host defense mechanisms. This study had two goals. First, determine the molecular basis of cholesterol homeostatic responses induced by the early region 3 membrane protein RIDα via its direct interaction with the sterol-binding protein ORP1L. Second, determine how this interaction regulates innate immunity to adenovirus...
January 11, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28074539/ritterostatin-gn1n-a-cephalostatin-ritterazine-bis-steroidal-pyrazine-hybrid-selectively-targets-grp78
#4
Andrew J Ambrose, Evelyne A Santos, Paula C Jimenez, Danilo D Rocha, Diego V Wilke, Paolo Beuzer, Josh Axelrod, Ananda Kumar Kanduluru, Philip L Fuchs, Hu Cang, Letícia V Costa-Lotufo, Eli Chapman, James J La Clair
Natural products discovered using agnostic approaches, unlike rationally designed or HTS obtained leads, offer the ability to reveal new biological pathways, and hence, serve as an important vehicle to unveil new avenues in drug discovery. The ritterazine-cephalostatin family of natural products displays robust and potent anti-tumor activities, with sub-nanomolar growth inhibition against multiple cell lines and potent activity in xenograft models. Herein, we use comparative cellular and molecular biological methods to uncover the ritterazine/cephalostatin mode of cytotoxic action (MOA) in human tumor cells...
January 10, 2017: Chembiochem: a European Journal of Chemical Biology
https://www.readbyqxmd.com/read/28067790/rab10-interacts-with-the-male-germ-cell-specific-gtpase-activating-protein-during-mammalian-spermiogenesis
#5
Ying-Hung Lin, Chih-Chun Ke, Ya-Yun Wang, Mei-Feng Chen, Tsung-Ming Chen, Wei-Chi Ku, Han-Sun Chiang, Chung-Hsin Yeh
According to recent estimates, 2%-15% of couples are sterile, and approximately half of the infertility cases are attributed to male reproductive factors. However, the reasons remain undefined in approximately 25% of male infertility cases, and most infertility cases exhibit spermatogenic defects. Numerous genes involved in spermatogenesis still remain unknown. We previously identified Male Germ Cells Rab GTPase-Activating Proteins (MGCRABGAPs) through cDNA microarray analysis of human testicular tissues with spermatogenic defects...
January 5, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28060560/harnessing-membrane-trafficking-to-promote-cancer-spreading-and-invasion-the-case-of-rab2a
#6
Hiroaki Kajiho, Yuko Kajiho, Giorgio Scita
How cancer disseminates and metastasizes remains an outstanding open question. Emerging evidence indicates that membrane trafficking is frequently harnessed by tumours of epithelial origin to acquire a mesenchymal program of invasiveness. However, the critical molecular hubs utilized by cancer cells this context have only began to be elucidated. Here, we discussed the results of a recent phenotypic screening that led to the identification of the small GTPase RAB2A, not previously involved in cancer dissemination, as pivotal for the acquisition of pericellular proteolysis, cell dissemination and distant metastatic spreading of human breast cancer...
January 6, 2017: Small GTPases
https://www.readbyqxmd.com/read/28056216/nuclear-localization-and-secretion-competence-is-conserved-amongst-henipavirus-matrix-proteins
#7
Elisabeth C McLinton, Kylie M Wagstaff, Alexander Lee, Gregory W Moseley, Glenn A Marsh, Lin-Fa Wang, David A Jans, Kim G Lieu, Hans Netter
Viruses of the genus Henipavirus of the family Paramyxoviridae are zoonotic pathogens, which have emerged in South East Asia, Australia and Africa. Nipah virus (NiV) and Hendra virus (HeV) are highly virulent pathogens transmitted from bats to animals and humans, whilst the henipavirus Cedar virus (CedV) seems to be non-pathogenic in infection studies. The full replication cycle of the Paramyxoviridae occurs in the host cell's cytoplasm where viral assembly is orchestrated by the matrix (M) protein. Unexpectedly, the NiV-M protein traffics through the nucleus as an essential step to engage the plasma membrane in preparation for viral budding/release...
January 5, 2017: Journal of General Virology
https://www.readbyqxmd.com/read/28053097/subcellular-localization-of-hiv-1-gag-pol-mrnas-regulates-sites-of-virion-assembly
#8
Jordan T Becker, Nathan M Sherer
: HIV-1 full-length, unspliced RNAs serve dual roles in the cytoplasm as mRNAs encoding the Gag and Gag-Pol capsid proteins as well as genomic RNAs (gRNAs) packaged by Gag into virions undergoing assembly at the plasma membrane (PM). Because Gag is sufficient to drive assembly of virus-like particles even in the absence of gRNA binding, whether viral RNA trafficking plays an active role in the native assembly pathway is unknown. In this study we tested the effects of modulating the cytoplasmic abundance or distribution of full-length viral RNAs on Gag trafficking and assembly in the context of single cells...
January 4, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28051846/selective-intracellular-delivery-of-ganglioside-gm3-binding-peptide-through-caveolae-raft-mediated-endocytosis
#9
Teruhiko Matsubara, Ryohei Otani, Miki Yamashita, Haruka Maeno, Hanae Nodono, Toshinori Sato
Glycosphingolipids are major components of the membrane raft, and several kinds of viruses and bacterial toxins are known to bind to glycosphingolipids in the membrane raft. Since the viral genes and pathogenic proteins that are taken into cells are directly delivered to their target organelles, caveolae/raft-mediated endocytosis represents a promising pathway for specific delivery. In the present study, we demonstrated the ability of an artificial pentadecapeptide, which binds to ganglioside GM3, to deliver protein into cells by caveolae/raft-mediated endocytosis...
January 4, 2017: Biomacromolecules
https://www.readbyqxmd.com/read/28051077/fig4-variants-in-central-european-patients-with-amyotrophic-lateral-sclerosis-a-whole-exome-and-targeted-sequencing-study
#10
Alma Osmanovic, Isolde Rangnau, Anne Kosfeld, Susanne Abdulla, Claas Janssen, Bernd Auber, Peter Raab, Matthias Preller, Susanne Petri, Ruthild G Weber
We aimed to identify the genetic cause of the devastating neurodegenerative disease amyotrophic lateral sclerosis (ALS) in a German family with two affected individuals, and to assess the prevalence of variants in the identified risk gene, FIG4, in a central European ALS cohort. Whole-exome sequencing (WES) and an overlapping data analysis strategy were performed in an ALS family with autosomal dominant inheritance and incomplete penetrance. Additionally, 200 central European ALS patients were analyzed using whole-exome or targeted sequencing...
January 4, 2017: European Journal of Human Genetics: EJHG
https://www.readbyqxmd.com/read/28049146/dissecting-bacterial-cell-wall-entry-and-signaling-in-eukaryotic-cells-an-actin-dependent-pathway-parallels-platelet-activating-factor-receptor-mediated-endocytosis
#11
Lip Nam Loh, Geli Gao, Elaine I Tuomanen
: The Gram-positive bacterial cell wall (CW) peptidoglycan-teichoic acid complex is released into the host environment during bacterial metabolism or death. It is a highly inflammatory Toll-like receptor 2 (TLR2) ligand, and previous in vivo studies have demonstrated its ability to recapitulate pathological features of pneumonia and meningitis. We report that an actin-dependent pathway is involved in the internalization of the CW by epithelial and endothelial cells, in addition to the previously described platelet-activating factor receptor (PAFr)-dependent uptake pathway...
January 3, 2017: MBio
https://www.readbyqxmd.com/read/28045926/survival-and-intra-nuclear-trafficking-of-burkholderia-pseudomallei-strategies-of-evasion-from-immune-surveillance
#12
Jamuna Vadivelu, Kumutha Malar Vellasamy, Jaikumar Thimma, Vanitha Mariappan, Wen-Tyng Kang, Leang-Chung Choh, Esaki M Shankar, Kum Thong Wong
BACKGROUND: During infection, successful bacterial clearance is achieved via the host immune system acting in conjunction with appropriate antibiotic therapy. However, it still remains a tip of the iceberg as to where persistent pathogens namely, Burkholderia pseudomallei (B. pseudomallei) reside/hide to escape from host immune sensors and antimicrobial pressure. METHODS: We used transmission electron microscopy (TEM) to investigate post-mortem tissue sections of patients with clinical melioidosis to identify the localisation of a recently identified gut microbiome, B...
January 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28045387/crystal-structure-of-truncated-human-coatomer-protein-complex-subunit-%C3%AE-1-cop%C3%AE-1
#13
Sergey Lunev, Marije F W Semmelink, Jia Ling Xian, Kai Yu Ma, Anna J A Leenders, Alexander S S Dömling, Michael Shtutman, Matthew R Groves
The majority of modern anticancer approaches target DNA/protein targets involved in tumour-cell proliferation. Such approaches have a major drawback, as nonproliferating cancer cells remain unaffected and may cause relapse or remission. Human coatomer protein complex I (COPI) subunit ζ (Copζ), a component of the coat protein involved in cell apoptosis and intracellular trafficking, has recently been proposed as a potential anticancer drug target. Previous studies have shown that two different isoforms of the Copζ subunit exist in mammalian cells...
January 1, 2017: Acta Crystallographica. Section F, Structural Biology Communications
https://www.readbyqxmd.com/read/28044359/mitochondria-in-complex-psychiatric-disorders-lessons-from-mouse-models-of-22q11-2-deletion-syndrome-hemizygous-deletion-of-several-mitochondrial-genes-in-the-22q11-2-genomic-region-can-lead-to-symptoms-associated-with-neuropsychiatric-disease
#14
Prakash Devaraju, Stanislav S Zakharenko
Mitochondrial ATP synthesis, calcium buffering, and trafficking affect neuronal function and survival. Several genes implicated in mitochondrial functions map within the genomic region associated with 22q11.2 deletion syndrome (22q11DS), which is a key genetic cause of neuropsychiatric diseases. Although neuropsychiatric diseases impose a serious health and economic burden, their etiology and pathogenesis remain largely unknown because of the dearth of valid animal models and the challenges in investigating the pathophysiology in neuronal circuits...
January 3, 2017: BioEssays: News and Reviews in Molecular, Cellular and Developmental Biology
https://www.readbyqxmd.com/read/28042950/ccl24-contributes-to-hcc-malignancy-via-rhob-vegfa-vegfr2-angiogenesis-pathway-and-indicates-poor-prognosis
#15
Lei Jin, Wei-Ren Liu, Meng-Xin Tian, Xi-Fei Jiang, Han Wang, Pei-Yun Zhou, Zhen-Bin Ding, Yuan-Fei Peng, Zhi Dai, Shuang-Jian Qiu, Jian Zhou, Jia Fan, Ying-Hong Shi
CCL24 is one chemotactic factor extensively studied in airway inflammation and colorectal cancer but less studied in hepatocellular carcinoma (HCC) retrospectively. So HCC tissue microarray (TMA) was used to estimate relationship between CCL24 and prognosis, cell experiments were conducted to study its influence for HCC cell biological behavior. CCL24 was injected to nude mice to monitor tumor formation and pulmonary metastasis; qRT-PCR, western blot and Immunohistochemistry were used to explore potential mechanism...
December 22, 2016: Oncotarget
https://www.readbyqxmd.com/read/28042091/novel-pde10a-transcript-diversity-in-the-human-striatum-insights-into-gene-complexity-conservation-and-regulation
#16
Courtney M MacMullen, Mohammad Fallahi, Ronald L Davis
PDE10A is a cAMP/cGMP phosphodiesterase important in signal transduction within medium spiny neurons of the human striatum. This gene region has been associated with bipolar disorder via case-control and linkage studies. The three most studied human PDE10A isoforms differ in both their N-termini and trafficking within the cell with PDE10A2 found predominantly at the plasma membrane and PDE10A1 and PDE10A19 remaining primarily within the cytosol. RNA-sequencing and 5' RLM-RACE studies of the human putamen and caudate nucleus revealed 16 new exons and 12 novel transcripts of PDE10A, 3 of which are predicted to produce proteins with unique N-termini...
December 29, 2016: Gene
https://www.readbyqxmd.com/read/28040639/poly-amidoamine-dendrimers-with-a-precisely-core-positioned-sulforhodamine-b-molecule-for-comparative-biological-tracing-and-profiling
#17
Lin-Ping Wu, Mario Ficker, Søren L Mejlsøe, Arnaldur Hall, Valentina Paolucci, Jørn B Christensen, Panagiotis N Trohopoulos, Seyed M Moghimi
We report on a simple robust procedure for synthesis of generation-4 poly-(amidoamine) (PAMAM) dendrimers with a precisely core positioned single sulforhodamine B molecule. The labelled dendrimers exhibited high fluorescent quantum yields where the absorbance and fluorescence spectrum of the fluorophore was not affected by pH and temperature. Since the stoichiometry of the fluorophore to the dendrimer is 1:1, we were able to directly compare uptake kinetics, the mode of uptake, trafficking and safety of dendrimers of different end-terminal functionality (carboxylated vs...
December 29, 2016: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28039913/the-unfolded-protein-response-mediates-fibrogenesis-and-collagen-i-secretion-through-regulating-tango1-in-mice
#18
Jessica L Maiers, Enis Kostallari, Malek Mushref, Thiago M deAssuncao, Haiyang Li, Nidhi Jalan-Sakrikar, Robert C Huebert, Sheng Cao, Harmeet Malhi, Vijay H Shah
: Fibrogenesis encompasses the deposition of matrix proteins, such as collagen I, by hepatic stellate cells (HSCs) that culminates in cirrhosis. Fibrogenic signals drive transcription of procollagen I, which enters the endoplasmic reticulum (ER), is trafficked through the secretory pathway, and released to generate extracellular matrix. Alternatively, disruption of procollagen I ER export could activate the unfolded protein response (UPR) and drive HSC apoptosis. Using a small interfering RNA screen, we identified Transport and Golgi organization 1 (TANGO1) as a potential participant in collagen I secretion...
November 5, 2016: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28035926/pleiotropic-effect-of-human-apoe4-on-cerebral-ceramide-and-saturated-fatty-acid-levels
#19
Sandra den Hoedt, Carola I F Janssen, Guiseppe Astarita, Daniele Piomelli, Frank P J Leijten, Simone M Crivelli, Adrie J M Verhoeven, Helga E de Vries, Jochen Walter, Pilar Martinez-Martinez, Eric J G Sijbrands, Amanda J Kiliaan, Monique T Mulder
BACKGROUND: Apolipoprotein E (ApoE) is known for its role in lipid trafficking and the ɛ4 allele is a risk factor for late onset Alzheimer's disease (AD). Recently, aberrant ceramide and fatty acid (FA) levels have been implicated in AD. OBJECTIVE: To determine the specific effects of human ApoE4 (hE4) on cerebral ceramide and FA content during chow or a high fat/high cholesterol (HFHC) diet. METHODS: Cerebral ceramide and FA profiles were determined by LC-MSMS in 15-month-old female wild-type (WT), ApoE-knockout (E0), and hE4-knockin mice fed chow or a HFHC diet for 3 months...
December 30, 2016: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28035533/mitochondrial-cholesterol-and-the-paradox-in-cell-death
#20
Carmen García-Ruiz, Vicente Ribas, Anna Baulies, Jose C Fernández-Checa
Mitochondria are considered cholesterol-poor organelles, and obtain their cholesterol load by the action of specialized proteins involved in its delivery from extramitochondrial sources and trafficking within mitochondrial membranes. Although mitochondrial cholesterol fulfills vital physiological functions, such as the synthesis of bile acids in the liver or the formation of steroid hormones in specialized tissues, recent evidence indicates that the accumulation of cholesterol in mitochondria may be a key event in prevalent human diseases, in particular in the development of steatohepatitis (SH) and its progression to hepatocellular carcinoma (HCC)...
December 30, 2016: Handbook of Experimental Pharmacology
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