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https://www.readbyqxmd.com/read/28431399/muc2-mucin-deficiency-alters-inflammatory-and-metabolic-pathways-in-the-mouse-intestinal-mucosa
#1
Selamawit Tadesse, Georgia Corner, Elena Dhima, Michele Houston, Chandan Guha, Leonard Augenlicht, Anna Velcich
The mucus layer in the intestine affects several aspects of intestinal biology, encompassing physical, chemical protection, immunomodulation and growth, thus contributing to homeostasis. Mice with genetic inactivation of the Muc2 gene, encoding the MUC2 mucin, the major protein component of mucus, exhibit altered intestinal homeostasis, which is strictly dependent on the habitat, likely due to differing complements of intestinal microbes. Our previous work established that Muc2 deficiency was linked to low chronic inflammation resulting in tumor development in the small, large intestine including the rectum...
April 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28431022/cpp1-phosphatase-mediated-signaling-crosstalk-between-hog1-and-cek1-mitogen-activated-protein-kinases-is-involved-in-the-phenotypic-transition-in-candida-albicans
#2
Fu-Sheng Deng, Ching-Hsuan Lin
Cellular signaling pathways involved in cell growth and differentiation mediated by mitogen-activated protein kinase (MAPK) cascades have been well characterized in fungi. However, the mechanisms of signaling crosstalk between MAPKs to ensure signaling specificity are largely unknown. Previous work showed that activation of the Candida albicans Cek1 MAPK pathway resulted in opaque cell formation and filamentation, which mirrored the phenotypes to hog1Δ. Additionally, deleting the HOG1 gene stimulated Cek1p...
April 20, 2017: Medical Mycology: Official Publication of the International Society for Human and Animal Mycology
https://www.readbyqxmd.com/read/28430817/kaposi-sarcoma-herpesvirus-kshv-latency-associated-nuclear-antigen-lana-recruits-components-of-the-mrn-mre11-rad50-nbs1-repair-complex-to-modulate-an-innate-immune-signaling-pathway-and-viral-latency
#3
Giuseppe Mariggiò, Sandra Koch, Guigen Zhang, Magdalena Weidner-Glunde, Jessica Rückert, Semra Kati, Susann Santag, Thomas F Schulz
Kaposi Sarcoma Herpesvirus (KSHV), a γ2-herpesvirus and class 1 carcinogen, is responsible for at least three human malignancies: Kaposi Sarcoma (KS), Primary Effusion Lymphoma (PEL) and Multicentric Castleman's Disease (MCD). Its major nuclear latency protein, LANA, is indispensable for the maintenance and replication of latent viral DNA in infected cells. Although LANA is mainly a nuclear protein, cytoplasmic isoforms of LANA exist and can act as antagonists of the cytoplasmic DNA sensor, cGAS. Here, we show that cytosolic LANA also recruits members of the MRN (Mre11-Rad50-NBS1) repair complex in the cytosol and thereby inhibits their recently reported role in the sensing of cytoplasmic DNA and activation of the NF-κB pathway...
April 21, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28428626/c1qbp-suppresses-cell-adhesion-and-metastasis-of-renal-carcinoma-cells
#4
Yong Wang, Donghe Fu, Jing Su, Yajing Chen, Can Qi, Yin Sun, Yuanjie Niu, Ning Zhang, Dan Yue
Complement component 1q subcomponent binding protein (C1QBP) is a ubiquitously expressed cellular protein and can be upregulated or activated in a variety of malignant tumors, including those from thyroid, colon and breast, but its role remains unclear in renal cell carcinoma (RCC). In this study, C1QBP knockdown in RCC cell influenced expression of multiple genes associated with cell adhesion, among which L1 cell adhesion molecule (L1CAM) was significantly higher upon a reduction of C1QBP. In turn, cell adhesion and invasion abilities were significantly increased with increased metastasis to lung and liver in vivo...
April 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28427159/genome-wide-analysis-of-long-noncoding-rna-and-mrna-co-expression-profile-in-intrahepatic-cholangiocarcinoma-tissue-by-rna-sequencing
#5
Wenhui Yang, Yuan Li, Xia Song, Jun Xu, Jun Xie
Long noncoding RNAs (lncRNAs), which are pervasively transcribed in the genome, are emerging in molecular biology as crucial regulators of cancer. RNA-seq data were downloaded from GEO of NCBI and further analyzed to identify novel targets in intrahepatic cholangiocarcinoma (iCCA).We investigated differences in lncRNA and mRNA profiles between 7 pairs of iCCA and adjacent normal tissues. 230 lncRNAs were differentially expressed more than four-fold change in iCCA tissues. Among these, 97 were upregulated and 133 downregulated relatively to normal tissues...
February 24, 2017: Oncotarget
https://www.readbyqxmd.com/read/28427099/role-of-phosphodiesterases-on-the-function-of-aryl-hydrocarbon-receptor-interacting-protein-aip-in-the-pituitary-gland-and-on-the-evaluation-of-aip-gene-variants
#6
Laura C Hernández-Ramírez, Giampaolo Trivellin, Constantine A Stratakis
Familial isolated pituitary adenoma (FIPA) is caused in about 20% of cases by loss-of-function germline mutations in the AIP gene. Patients harboring AIP mutations usually present with somatotropinomas resulting either in gigantism or young-onset acromegaly. AIP encodes for a co-chaperone protein endowed with tumor suppressor properties in somatotroph cells. Among other mechanisms proposed to explain this function, a regulatory effect over the 3',5'-cyclic adenosine monophosphate (cAMP) signaling pathway seems to play a prominent role...
April 2017: Hormone and Metabolic Research, Hormon- und Stoffwechselforschung, Hormones et Métabolisme
https://www.readbyqxmd.com/read/28426722/interactions-between-mitoneet-and-naf-1-in-cells
#7
Ola Karmi, Sarah H Holt, Luhua Song, Sagi Tamir, Yuting Luo, Fang Bai, Ammar Adenwalla, Merav Darash-Yahana, Yang-Sung Sohn, Patricia A Jennings, Rajeev K Azad, Jose' N Onuchic, Faruck Morcos, Rachel Nechushtai, Ron Mittler
The NEET proteins mitoNEET (mNT) and nutrient-deprivation autophagy factor-1 (NAF-1) are required for cancer cell proliferation and resistance to oxidative stress. NAF-1 and mNT are also implicated in a number of other human pathologies including diabetes, neurodegeneration and cardiovascular disease, as well as in development, differentiation and aging. Previous studies suggested that mNT and NAF-1 could function in the same pathway in mammalian cells, preventing the over-accumulation of iron and reactive oxygen species (ROS) in mitochondria...
2017: PloS One
https://www.readbyqxmd.com/read/28426665/oncodomains-a-protein-domain-centric-framework-for-analyzing-rare-variants-in-tumor-samples
#8
Thomas A Peterson, Iris Ivy M Gauran, Junyong Park, DoHwan Park, Maricel G Kann
The fight against cancer is hindered by its highly heterogeneous nature. Genome-wide sequencing studies have shown that individual malignancies contain many mutations that range from those commonly found in tumor genomes to rare somatic variants present only in a small fraction of lesions. Such rare somatic variants dominate the landscape of genomic mutations in cancer, yet efforts to correlate somatic mutations found in one or few individuals with functional roles have been largely unsuccessful. Traditional methods for identifying somatic variants that drive cancer are 'gene-centric' in that they consider only somatic variants within a particular gene and make no comparison to other similar genes in the same family that may play a similar role in cancer...
April 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/28426283/identification-of-the-proteome-complement-of-humantlk1-reveals-it-binds-and-phosphorylates-nek1-regulating-its-activity
#9
Vibha Singh, Zachary M Connelly, Xinggui Shen, Arrigo De Benedetti
The Tousled Like kinases (TLKs) are involved in numerous cellular functions, including the DNA Damage Response (DDR), but only a handful of substrates have been identified thus far. Through a novel proteomic screen, we have now identified 165 human proteins interacting with TLK1, and we have focused this work on NEK1 because of its known role in the DDR, upstream of ATR and Chk1. TLK1 and NEK1 were found to interact by coIP, and their binding is strengthened following exposure of cells to H2O2. Following incubation with doxorubicin, TLK1 and NEK1 relocalize with nuclear repair foci along with γH2AX...
April 20, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28426228/ultrafast-dynamics-of-a-triazene-excited-state-pathways-and-the-impact-of-binding-to-the-minor-groove-of-dna-and-further-biomolecular-systems
#10
Lena Grimmelsmann, Alireza Marefat Khah, Christian Spies, Christof Hättig, Patrick Nuernberger
Many synthetic DNA minor groove binders exhibit a strong increase in fluorescence when bound to DNA. The pharmaceutical-relevant berenil (diminazene aceturate) is an exception with an extremely low fluorescence quantum yield (on the order of 10(-4)). We investigate the ultrafast excited-state dynamics of this triazene by femtosecond time-resolved fluorescence experiments in water, ethylene glycol, and buffer and bound to the enzyme β-trypsin, the minor groove of AT-rich DNA, and G-quadruplex DNA. Ab initio calculations provide additional mechanistic insight...
April 20, 2017: Journal of Physical Chemistry Letters
https://www.readbyqxmd.com/read/28424845/the-regulatory-role-of-the-transcription-factor-crz1-in-stress-tolerance-pathogenicity-and-its-target-gene-expression-in-metarhizium-acridum
#11
Xing Chen, Yuanze Liu, Nemat O Keyhani, Yuxian Xia, Yueqing Cao
In fungi, the Ca(2+)/calcineurin signaling pathway is critical in mediating growth, morphology, stress responses, and pathogenicity. Crz1 is a calcineurin-responsive zinc finger transcription factor. Here, MaCrz1 was identified and functionally characterized in the entomopathogenic fungus Metarhizium acridum by characterization of a targeted gene knockout strain. Conidia of the ΔMacrz1 mutant were aberrant in cell surface features and lacked the characteristic hydrophobic rodlet layer, and the mutant displayed increased sensitivity to oxidative stress, cell wall perturbing agents, heat stress, and ultraviolet irradiation as compared to the wild-type and complemented strains...
April 19, 2017: Applied Microbiology and Biotechnology
https://www.readbyqxmd.com/read/28424709/evolutionary-analysis-of-snf1-related-protein-kinase2-snrk2-and-calcium-sensor-scs-gene-lineages-and-dimerization-of-rice-homologs-suggest-deep-biochemical-conservation-across-angiosperms
#12
Lynn D Holappa, Pamela C Ronald, Elena M Kramer
Members of the sucrose non-fermenting related kinase Group2 (SnRK2) subclasses are implicated in both direct and indirect abscisic acid (ABA) response pathways. We have used phylogenetic, biochemical, and transient in vivo approaches to examine interactions between Triticum tauschii protein kinase 1 (TtPK1) and an interacting protein, Oryza sativa SnRK2-calcium sensor (OsSCS1). Given that TtPK1 has 100% identity with its rice ortholog, osmotic stress/ABA-activated protein kinase (OsSAPK2), we hypothesized that the SCS and TtPK1 interactions are present in both wheat and rice...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/28424618/pharmacological-and-biochemical-characterization-of-tlqp-21-activation-of-a-binding-site-on-cho-cells
#13
Laura Molteni, Laura Rizzi, Elena Bresciani, Roberta Possenti, Pamela Petrocchi Passeri, Corrado Ghè, Giampiero Muccioli, Jean-Alain Fehrentz, Pascal Verdié, Jean Martinez, Robert J Omeljaniuk, Giuseppe Biagini, Anna Binda, Ilaria Rivolta, Vittorio Locatelli, Antonio Torsello
VGF is a propeptide of 617 amino acids expressed throughout the central and the peripheral nervous system. VGF and peptides derived from its processing have been found in dense core vesicles and are released from neuronal and neuroendocrine cells via the regulated secretory pathway. Among VGF-derived neuropeptides, TLQP-21 (VGF(556-576)) has raised a huge interest and is one of most studied. TLQP-21 is a multifunctional neuropeptide involved in the control of several physiological functions, potentially including energy homeostasis, pain modulation, stress responsiveness and reproduction...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28424577/investigation-of-endocytic-pathways-for-the-internalization-of-exosome-associated-oligomeric-alpha-synuclein
#14
Marion Delenclos, Teodora Trendafilova, Divya Mahesh, Ann M Baine, Simon Moussaud, Irene K Yan, Tushar Patel, Pamela J McLean
Misfolding and aggregation of alpha-synuclein (αsyn) resulting in cytotoxicity is a hallmark of Parkinson's disease (PD) and related synucleinopathies. The recent body of evidence indicates that αsyn can be released from neuronal cells by nonconventional exocytosis involving extracellular vesicles (EVs) such as exosomes. The transfer of αsyn between cells has been proposed to be an important mechanism of disease propagation in PD. To date, exosome trafficking mechanisms, including release and cell-cell transmission, have not been fully described...
2017: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/28423024/interrelationships-of-vel1-and-env1-in-light-response-and-development-in-trichoderma-reesei
#15
Hoda Bazafkan, Christoph Dattenböck, Eva Stappler, Sabrina Beier, Monika Schmoll
Sexual development is regulated by a complex regulatory mechanism in fungi. For Trichoderma reesei, the light response pathway was shown to impact sexual development, particularly through the photoreceptor ENVOY. Moreover, T. reesei communicates chemically with a potential mating partner in its vicinity, a response which is mediated by the velvet family protein VEL1 and its impact on secondary metabolism. We therefore studied the regulatory interactions of ENV1 and VEL1 with a focus on sexual development. Although individual mutants in both genes are female sterile under standard crossing conditions (light-dark cycles), an altered light regime enabled sexual development, which we found to be due to conditional female sterility of Δenv1, but not Δvel1...
2017: PloS One
https://www.readbyqxmd.com/read/28422127/differential-control-of-asexual-development-and-sterigmatocystin-biosynthesis-by-a-novel-regulator-in-aspergillus-nidulans
#16
Yong Jin Kim, Yu Yeong Man, Pil Jae Maeng
The filamentous fungus Aspergillus nidulans primarily reproduces by forming asexual spores called conidia and produces the mycotoxin sterigmatocystin (ST), the penultimate precursor of aflatoxins. It has been known that asexual development and ST production are tightly co-regulated by various regulatory inputs. Here, we report that the novel regulator AslA with a C2H2 domain oppositely regulates development and ST biosynthesis. Nullifying aslA resulted in defective conidiation and reduced expression of brlA encoding a key activator of asexual development, which indicates that AslA functions as an upstream activator of brlA expression...
April 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28421329/characterization-of-two-tt2-type-myb-transcription-factors-regulating-proanthocyanidin-biosynthesis-in-tetraploid-cotton-gossypium-hirsutum
#17
Nan Lu, Marissa Roldan, Richard A Dixon
Two TT2-type MYB transcription factors identified from tetraploid cotton are involved in regulating proanthocyanidin biosynthesis, providing new strategies for engineering condensed tannins in crops. Proanthocyanidins (PAs), also known as condensed tannins, are important secondary metabolites involved in stress resistance in plants, and are health supplements that help to reduce cholesterol levels. As one of the most widely grown crops in the world, cotton provides the majority of natural fabrics and is a supplemental food for ruminant animals...
April 18, 2017: Planta
https://www.readbyqxmd.com/read/28421096/regulation-of-banana-phytoene-synthase-mapsy-expression-characterization-and-their-modulation-under-various-abiotic-stress-conditions
#18
Navneet Kaur, Ashutosh Pandey, Shivani, Prateek Kumar, Pankaj Pandey, Atul K Kesarwani, Shrikant S Mantri, Praveen Awasthi, Siddharth Tiwari
Phytoene synthase (PSY) is a key regulatory enzyme of carotenoid biosynthesis pathway in plants. The present study examines the role of PSY in carotenogenesis and stress management in banana. Germplasm screening of 10 Indian cultivars showed that Nendran (3011.94 μg/100 g dry weight) and Rasthali (105.35 μg/100 g dry weight) contained the highest and lowest amounts of β-carotene, respectively in ripe fruit-pulp. Nendran ripe pulp also showed significantly higher antioxidant activity as compared to Rasthali...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/28418235/discovery-of-the-showdomycin-gene-cluster-from-streptomyces-showdoensis-atcc-15227-yields-insight-into-the-biosynthetic-logic-of-c-nucleoside-antibiotics
#19
Kaisa Palmu, Petja Rosenqvist, Keshav Thapa, Yulia Ilina, Vilja Siitonen, Bikash Baral, Janne Mäkinen, Georgi Belogurov, Pasi Virta, Jarmo Niemi, Mikko Metsä-Ketelä
Nucleoside antibiotics are a large class of pharmaceutically relevant chemical entities, which exhibit a broad spectrum of biological activities. Most nucleosides belong to the canonical N-nucleoside family, where the heterocyclic unit is connected to the carbohydrate through a carbon-nitrogen bond. However, atypical C-nucleosides have been isolated from Streptomyces bacteria over 50 years ago, but the molecular basis for formation of these metabolites has been unknown. Here we have sequenced the genome of S...
April 18, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/28416734/the-angiotensin-receptor-blocker-losartan-inhibits-mammary-tumor-development-and-progression-to-invasive-carcinoma
#20
Rhiannon Coulson, Seng H Liew, Angela A Connelly, Nicholas S Yee, Siddhartha Deb, Beena Kumar, Ana C Vargas, Sandra A O'Toole, Adam C Parslow, Ashleigh Poh, Tracy Putoczki, Riley J Morrow, Mariah Alorro, Kyren A Lazarus, Evie F W Yeap, Kelly L Walton, Craig A Harrison, Natalie J Hannan, Amee J George, Colin D Clyne, Matthias Ernst, Andrew M Allen, Ashwini L Chand
Drugs that target the Renin-Angiotensin System (RAS) have recently come into focus for their potential utility as cancer treatments. The use of Angiotensin Receptor Blockers (ARBs) and Angiotensin-Converting Enzyme (ACE) Inhibitors (ACEIs) to manage hypertension in cancer patients is correlated with improved survival outcomes for renal, prostate, breast and small cell lung cancer. Previous studies demonstrate that the Angiotensin Receptor Type I (AT1R) is linked to breast cancer pathogenesis, with unbiased analysis of gene-expression studies identifying significant up-regulation of AGTR1, the gene encoding AT1R in ER+ve/HER2-ve tumors correlating with poor prognosis...
March 21, 2017: Oncotarget
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