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https://www.readbyqxmd.com/read/28224663/loss-of-mlh1-sensitizes-colon-cancer-cells-to-dna-pkcs-inhibitor-ku60648
#1
Inga Hinrichsen, Anne Ackermann, Tonja Düding, Annika Graband, Natalie Filmann, Guido Plotz, Stefan Zeuzem, Angela Brieger
Germline mutations of MLH1 are responsible for tumor generation in nearly 50% of patients with Lynch Syndrome, and around 15% of sporadic colorectal cancers show MLH1-deficiency due to promotor hypermethylation. Although these tumors are of lower aggressiveness the benefit for these patients from standard chemotherapy is still under discussion. Recently, it was shown that the sensitivity to the DNA-PKcs inhibitor KU60648 is linked to loss of the MMR protein MSH3. However, loss of MSH3 is rather secondary, as a consequence of MMR-deficiency, and frequently detectable in MLH1-deficient tumors...
February 22, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28223944/il-1%C3%AE-induced-downregulation-of-the-multifunctional-pdz-adaptor-pdzk1-is-attenuated-by-erk-inhibition-rxr%C3%AE-or-ppar%C3%AE-stimulation-in-enterocytes
#2
Min Luo, Sunil Yeruva, Yongjian Liu, Giriprakash Chodisetti, Brigitte Riederer, Manoj B Menon, Keisuke Tachibana, Takefumi Doi, Ursula E Seidler
Background: The PDZ adaptor protein PDZK1 modulates the membrane expression and function of a variety of intestinal receptors and ion/nutrient transporters. Its expression is strongly decreased in inflamed intestinal mucosa of mice and IBD patients. Aim and Methods: We investigated whether the inflammation-associated PDZK1 downregulation is a direct consequence of proinflammatory cytokine release by treating intestinal Caco-2BBE cells with TNF-α, IFN-γ, and IL-1β, and analysing PDZK1 promotor activity, mRNA and protein expression...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28221784/development-of-a-biosensor-concept-to-detect-the-production-of-cluster-specific-secondary-metabolites
#3
Yi-Qian Sun, Tobias Busche, Christian Rückert, Constanze Paulus, Yuriy Rebets, Renata Novakova, Joern Kalinowski, Andriy Luzhetskyy, Jan Kormanec, Olga N Sekurova, Sergey B Zotchev
Genome mining of actinomycete bacteria aims at the discovery of novel bioactive secondary metabolites that can be developed into drugs. A new repressor-based biosensor to detect activated secondary metabolite biosynthesis gene clusters in Streptomyces was developed. Biosynthetic gene clusters for undecylprodigiosin and coelimycin in the genome of Streptomyces lividans TK24, which encoded TetR-like repressors and appeared to be almost "silent" based on the RNA-seq data were chosen for the proof-of-principle studies...
February 21, 2017: ACS Synthetic Biology
https://www.readbyqxmd.com/read/28215381/intervention-effects-on-latinas-physical-activity-and-other-health-indicators
#4
Guadalupe X Ayala, Marisa Molina, Hala Madanat, Jeanne F Nichols, Thomas L McKenzie, Ming Ji, Margarita Holguin, Lisa Cuestas, Caryn Sumek, Carolina Labarca, Sandra Elvira, Elva M Arredondo, John P Elder
INTRODUCTION: U.S. Latinas do not engage in sufficient leisure-time physical activity. This study examined whether adding promotor-facilitated healthy lifestyle classes to an exercise intervention would promote exercise session attendance and improve health indicators. METHODS: The Familias Sanas y Activas II (Healthy and Active Families II) study used a within-subjects, longitudinal design, with measures at baseline and at 6 and 12 months post-baseline. The intervention was developed by the San Diego Prevention Research Center and implemented between May 2011 and June 2014 in South San Diego County...
March 2017: American Journal of Preventive Medicine
https://www.readbyqxmd.com/read/28212656/using-a-vector-pool-containing-variable-strength-promoters-to-optimize-protein-production-in-yarrowia-lipolytica
#5
Rémi Dulermo, François Brunel, Thierry Dulermo, Rodrigo Ledesma-Amaro, Jérémy Vion, Marion Trassaert, Stéphane Thomas, Jean-Marc Nicaud, Christophe Leplat
BACKGROUND: The yeast Yarrowia lipolytica is an increasingly common biofactory. To enhance protein expression, several promoters have been developed, including the constitutive TEF promoter, the inducible POX2 promotor, and the hybrid hp4d promoter. Recently, new hp4d-inspired promoters have been created that couple various numbers of UAS1 tandem elements with the minimal LEU2 promoter or the TEF promoter. Three different protein-secretion signaling sequences can be used: preLip2, preXpr2, and preSuc2...
February 17, 2017: Microbial Cell Factories
https://www.readbyqxmd.com/read/28210208/promoter-specific-expression-and-genomic-structure-of-iglon-family-genes-in-mouse
#6
Taavi Vanaveski, Katyayani Singh, Jane Narvik, Kattri-Liis Eskla, Tanel Visnapuu, Indrek Heinla, Mohan Jayaram, Jürgen Innos, Kersti Lilleväli, Mari-Anne Philips, Eero Vasar
IgLON family is composed of five genes: Lsamp, Ntm, Opcml, Negr1, and Iglon5; encoding for five highly homologous neural adhesion proteins that regulate neurite outgrowth and synapse formation. In the current study we performed in silico analysis revealing that Ntm and Opcml display similar genomic structure as previously reported for Lsamp, characterized by two alternative promotors 1a and 1b. Negr1 and Iglon5 transcripts have uniform 5' region, suggesting single promoter. Iglon5, the recently characterized family member, shares high level of conservation and structural qualities characteristic to IgLON family such as N-terminal signal peptide, three Ig domains, and GPI anchor binding site...
2017: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/28208742/aav-vector-mediated-gene-delivery-to-substantia-nigra-dopamine-neurons-implications-for-gene-therapy-and-disease-models
#7
REVIEW
Katrina Albert, Merja H Voutilainen, Andrii Domanskyi, Mikko Airavaara
Gene delivery using adeno-associated virus (AAV) vectors is a widely used method to transduce neurons in the brain, especially due to its safety, efficacy, and long-lasting expression. In addition, by varying AAV serotype, promotor, and titer, it is possible to affect the cell specificity of expression or the expression levels of the protein of interest. Dopamine neurons in the substantia nigra projecting to the striatum, comprising the nigrostriatal pathway, are involved in movement control and degenerate in Parkinson's disease...
February 8, 2017: Genes
https://www.readbyqxmd.com/read/28203148/dopamine-d1-receptor-immunoreactivity-on-fine-processes-of-gfap-positive-astrocytes-in-the-substantia-nigra-pars-reticulata-of-adult-mouse
#8
Katsuhiro Nagatomo, Sechiko Suga, Masato Saitoh, Masahito Kogawa, Kazuto Kobayashi, Yoshio Yamamoto, Katsuya Yamada
Substantia nigra pars reticulata (SNr), the major output nucleus of the basal ganglia, receives dopamine from dendrites extending from dopaminergic neurons of the adjacent nucleus pars compacta (SNc), which is known for its selective degeneration in Parkinson's disease. As a recipient for dendritically released dopamine, the dopamine D1 receptor (D1R) is a primary candidate due to its very dense immunoreactivity in the SNr. However, the precise location of D1R remains unclear at the cellular level in the SNr except for that reported on axons/axon terminals of presumably striatal GABAergic neurons...
2017: Frontiers in Neuroanatomy
https://www.readbyqxmd.com/read/28196395/spread-of-tau-down-neural-circuits-precedes-synapse-and-neuronal-loss-in-the-rtgtauec-mouse-model-of-early-alzheimer-s-disease
#9
Eleanor K Pickett, Christopher M Henstridge, Elizabeth Allison, Rose Pitstick, Amy Pooler, Susanne Wegmann, George Carlson, Bradley T Hyman, Tara L Spires-Jones
Synaptic dysfunction and loss is the strongest pathological correlate of cognitive decline in Alzheimer's disease (AD) with increasing evidence implicating neuropathological tau protein in this process. Despite the knowledge that tau spreads through defined synaptic circuits, it is currently unknown whether synapse loss occurs before the accumulation of tau or as a consequence. To address this, we have used array tomography to examine an rTgTauEC mouse model expressing a P301L human tau transgene and a transgene labelling cytoplasm red (tdTomato) and presynaptic terminals green (Synaptophysin-EGFP)...
February 14, 2017: Synapse
https://www.readbyqxmd.com/read/28157665/inhibition-of-cancer-migration-and-invasion-by-knocking-down-delta-5-desaturase-in-cox-2-overexpressed-cancer-cells
#10
Xiaoyu Yang, Yi Xu, Tao Wang, Dan Shu, Peixuan Guo, Keith Miskimins, Steven Y Qian
We recently reported that knockdown of delta-5-desaturase (a key enzyme that converts dihomo-γ-linolenic acid, DGLA, to the downstream ω-6 arachidonic acid) promotes formation of an anti-cancer byproduct 8-hydroxyoctanoic acid from cyclooxygenase (COX)-catalyzed DGLA peroxidation. 8-hydroxyoctanoic acid can exert its growth inhibitory effect on cancer cells (e.g. colon and pancreatic cancer) by serving as a histone deacetylase inhibitor. Since histone deacetylase inhibitors have been well-known to suppress cancer cell migration and invasion, we thus tested whether knockdown of delta-5-desaturase and DGLA treatment could also be used to inhibit cancer migration and invasion of colon cancer and pancreatic cancer cells...
January 26, 2017: Redox Biology
https://www.readbyqxmd.com/read/28139105/-establishment-of-a-preclinical-neuroblastoma-model-in-immunocompetent-mice
#11
A L Luis, M Espinoza, L Franco, A González-Murillo, G J Melen, J C Ollero Fresno, L Madero, M Ramírez
AIM: To develop a NB animal model which makes possible studies related to tumor immunity. MATERIALS AND METHODS: Two types of NB cells were used. Cell line 36769 was derived from TH-MYCN+ mouse in which overexpression of the MYCN gene is governed by rat tyrosine hydroxylase promotor. Cell line 4040 was derived from TH-MYCN/ALK mice, which in addition express an activating mutation of ALK gene. For each cell type, 1x10(6) neurospheres were implanted in 129/SVJ mice (with the same genetic background as donors, n=8), via orthotopic injection in the left suprarenal gland by intraperitoneal approach, through a transverse supraumbilical laparotomy...
April 10, 2016: Cirugía Pediátrica: Organo Oficial de la Sociedad Española de Cirugía Pediátrica
https://www.readbyqxmd.com/read/28138698/dose%C3%A2-dependent-effect-of-lysozyme-upon-candida%C3%A2-albicans-biofilm
#12
Sarra Sebaa, Nicolas Hizette, Zahia Boucherit-Otmani, Philippe Courtois
The present study investigated the in vitro effect of lysozyme (0-1,000 µg/ml) on Candida albicans (C. albicans) biofilm development. Investigations were conducted on C. albicans ATCC 10231 and on 10 clinical isolates from dentures. Strains were cultured aerobically at 37˚C in Sabouraud broth. Yeast growth was evaluated by turbidimetry. Biofilm biomass was quantified on a polystyrene support by crystal violet staining and on acrylic surfaces by counts of colony forming units. Lysozyme affected biofilm formation to a greater extent than it affected growth...
January 25, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28105082/genetic-diagnosis-and-treatment-of-a-chinese-ketosis-prone-mody-3-family-with-depression
#13
Jun Tang, Chen-Yi Tang, Fang Wang, Yue Guo, Hao-Neng Tang, Ci-La Zhou, Shu-Wen Tan, Shi-Ping Liu, Zhi-Guang Zhou, Hou-De Zhou
BACKGROUND: To analyze the gene mutation and mental disorder of a Chinese ketosis-prone diabetes (KPD) family, and to make a precise diagnosis and give a treatment for them. METHODS: We studied a Chinese family with a clinical diagnosis of maturity-onset diabetes of the young (MODY). The clinical data and the blood samples were collected. The promotor and coding regions inclusive intron exon boundaries of the HNF1A, HNF4A were detected by polymerase chain reaction (PCR) and direct sequencing...
2017: Diabetology & Metabolic Syndrome
https://www.readbyqxmd.com/read/28104469/culturally-grounded-diabetes-prevention-program-for-obese-latino-youth-rationale-design-and-methods
#14
Allison N Williams, Yolanda P Konopken, Colleen S Keller, Felipe Gonzalez Castro, Kimberly J Arcoleo, Estela Barraza, Donald L Patrick, Micah L Olson, Gabriel Q Shaibi
BACKGROUND: Type 2 diabetes (T2D) disproportionately impacts Latino youth yet few diabetes prevention programs address this important source of health disparities. OBJECTIVES: To address this knowledge gap, we describe the rationale, design, and methodology underpinning a culturally-grounded T2D prevention program for obese Latino youth. The study aims to: 1) to test the efficacy of the intervention for reducing T2D risk, 2) explore potential mediators and moderators of changes in health behaviors and health outcomes and, 3) examine the incremental cost-effectiveness for reducing T2D risk...
March 2017: Contemporary Clinical Trials
https://www.readbyqxmd.com/read/28077174/mutant-hspb1-causes-loss-of-translational-repression-by-binding-to-pcbp1-an-rna-binding-protein-with-a-possible-role-in-neurodegenerative-disease
#15
Thomas Geuens, Vicky De Winter, Nicholas Rajan, Tilmann Achsel, Ligia Mateiu, Leonardo Almeida-Souza, Bob Asselbergh, Delphine Bouhy, Michaela Auer-Grumbach, Claudia Bagni, Vincent Timmerman
The small heat shock protein HSPB1 (Hsp27) is an ubiquitously expressed molecular chaperone able to regulate various cellular functions like actin dynamics, oxidative stress regulation and anti-apoptosis. So far disease causing mutations in HSPB1 have been associated with neurodegenerative diseases such as distal hereditary motor neuropathy, Charcot-Marie-Tooth disease and amyotrophic lateral sclerosis. Most mutations in HSPB1 target its highly conserved α-crystallin domain, while other mutations affect the C- or N-terminal regions or its promotor...
January 11, 2017: Acta Neuropathologica Communications
https://www.readbyqxmd.com/read/28074418/identification-of-low-molecular-weight-vitellogenin-1-vg1-like-proteins-as-nucleotide-excision-repair-ner-factors-in-developing-zebrafish-danio-rerio-using-a-transcription-based-dna-repair-assay
#16
Yung-Chi Shen, Todd Hsu, Li-Bin Ling, Wen-Chian You, Chia-Wei Liu
Nucleotide excision repair (NER) removes helix-distorting DNA lesions such as UV-induced pyrimidine dimers and cisplatin-induced strand crosslinking. Our earlier studies have identified low-molecular-weight proteins homologous to the 150-kDa vitellogenin 1 (Vg1) as UV-damaged DNA-binding factors expressed in developing zebrafish (Danio rerio). This present study explored if Vg1-like proteins also participated in NER in zebrafish. Immunoblot analysis of affinity-captured 12 h post-fertilization (hpf) zebrafish extract proteins showed a transient binding of a 30-kDa Vg1-like polypeptide to UV-damaged DNA...
January 10, 2017: Fish Physiology and Biochemistry
https://www.readbyqxmd.com/read/28068366/overproduction-of-%C3%AE-lipoic-acid-by-gene-manipulated-escherichia-coli
#17
Yirong Sun, Wenbin Zhang, Jincheng Ma, Hongshen Pang, Haihong Wang
Alpha-lipoic acid (LA) is an important enzyme cofactor widely used by organisms and is also a natural antioxidant for the treatment of pathologies driven by low levels of endogenous antioxidants. In order to establish a safer and more efficient process for LA production, we developed a new biological method for LA synthesis based on the emerging knowledge of lipoic acid biosynthesis. We first cloned the lipD gene, which encodes the lipoyl domain of the E2 subunit of pyruvate dehydrogenase, allowing high levels of LipD production...
2017: PloS One
https://www.readbyqxmd.com/read/28060940/clock-genes-regulate-the-circadian-expression-of-piezo1-trpv4-connexin26-and-vnut-in-an-ex-vivo-mouse-bladder-mucosa
#18
Tatsuya Ihara, Takahiko Mitsui, Yuki Nakamura, Satoru Kira, Hiroshi Nakagomi, Norifumi Sawada, Yuri Hirayama, Keisuke Shibata, Eiji Shigetomi, Yoichi Shinozaki, Mitsuharu Yoshiyama, Karl-Erik Andersson, Atsuhito Nakao, Masayuki Takeda, Schuichi Koizumi
OBJECTIVES: ClockΔ19/Δ19 mice is an experimental model mouse for nocturia (NOC). Using the bladder mucosa obtained from ClockΔ19/Δ19 mice, we investigated the gene expression rhythms of mechanosensory cation channels such as transient receptor potential cation channel subfamily V member 4 (TRPV4) and Piezo1, and main ATP release pathways including vesicular nucleotide transporter (VNUT) and Connexin26(Cx26), in addition to clock genes. MATERIALS AND METHODS: Eight- to twelve-week-old male C57BL/6 mice (WT) and age- and sex-matched C57BL/6 ClockΔ19/Δ19 mice, which were bred under 12-h light/dark conditions for 2 weeks, were used...
2017: PloS One
https://www.readbyqxmd.com/read/28056258/-advance-of-molecular-subtyping-and-precise-treatment-for-gliomas
#19
W Hua, Y Mao
With the advance of genomics research, there have been a new breakthrough in the molecular classification of gliomas. Glioblastoma (WHO grade Ⅳ) could be subtyped to proneural, neural, classical, and mesochymal according to the mRNA expression. Lower grade gliomas (WHO grade Ⅱ and Ⅲ) could be divided into 5 types using 1p/19q co-deletion, isocitrate dehydrogenase(IDH) mutation, and TERTp (promotor region) mutation. In 2016, a new classification of tumors of the central nervous system was proposed, and some new markers such as IDH1 mutation were introduced into the diagnosis of gliomas...
1, 2017: Zhonghua Wai Ke za Zhi [Chinese Journal of Surgery]
https://www.readbyqxmd.com/read/28049753/behavioral-lifestyle-interventions-for-the-primary-prevention-of-type-2-diabetes-and-translation-to-hispanic-latino-communities-in-the-united-states-and-mexico
#20
Elizabeth M Venditti
Lifestyle behaviors in overweight and obese individuals are closely linked to the development, course, and outcomes of type 2 diabetes and multiple comorbid health conditions. Behavior change theory and many randomized controlled studies offer strong support for screening and identifying adults at increased cardiometabolic risk and for providing early intervention to mitigate risk factors to prevent or delay the onset of disease. The current article reviews key lifestyle intervention efficacy and dissemination trials conducted with individuals deemed to be at increased risk for diabetes and describes the rationale for training teams of professionals and community health workers (e...
January 2017: Nutrition Reviews
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