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https://www.readbyqxmd.com/read/29037065/patterns-of-symptom-development-in-patients-with-motor-neuron-disease
#1
Renée Walhout, Esther Verstraete, Martijn P Van Den Heuvel, Jan H Veldink, Leonard H Van Den Berg
OBJECTIVE: To investigate whether symptom development in motor neuron disease (MND) is a random or organized process. METHODS: Six hundred patients with amyotrophic lateral sclerosis (ALS), upper motor neuron (UMN) or lower motor neuron (LMN) phenotypes were invited for a questionnaire concerning symptom development. A binomial test was used to examine distribution of symptoms from site of onset. Development of symptoms over time was evaluated by Kaplan-Meier analysis...
October 16, 2017: Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration
https://www.readbyqxmd.com/read/28791781/many-transcription-factors-contribute-to-c-%C3%A2-elegans-growth-and-fat-storage
#2
Akihiro Mori, Amy D Holdorf, Albertha J M Walhout
Reverse genetic screens by RNA interference (RNAi) in model organisms such as the nematode Caenorhabditis elegans have provided numerous insights into gene function, thereby connecting genotype to phenotype. However, genes that contribute only subtly are often missed because relatively large numbers of measurements and reliable quantification are required to overcome experimental and biological noise that may mask subtle phenotypic effects. Here, we address this challenge by focusing on two phenotypes in C...
September 2017: Genes to Cells: Devoted to Molecular & Cellular Mechanisms
https://www.readbyqxmd.com/read/28702278/prima-a-gene-centered-rna-to-protein-method-for-mapping-rna-protein-interactions
#3
Alex M Tamburino, Ebru Kaymak, Shaleen Shrestha, Amy D Holdorf, Sean P Ryder, Albertha J M Walhout
Interactions between RNA binding proteins (RBPs) and mRNAs are critical to post-transcriptional gene regulation. Eukaryotic genomes encode thousands of mRNAs and hundreds of RBPs. However, in contrast to interactions between transcription factors (TFs) and DNA, the interactome between RBPs and RNA has been explored for only a small number of proteins and RNAs. This is largely because the focus has been on using 'protein-centered' (RBP-to-RNA) interaction mapping methods that identify the RNAs with which an individual RBP interacts...
2017: Translation
https://www.readbyqxmd.com/read/28600327/the-oxidative-stress-response-in-caenorhabditis-elegans-requires-the-gata-transcription-factor-elt-3-and-skn-1-nrf2
#4
Queenie Hu, Dayana R D'Amora, Lesley T MacNeil, Albertha J M Walhout, Terrance J Kubiseski
Cellular damage caused by reactive oxygen species is believed to be a major contributor to age-associated diseases. Previously, we characterized the Caenorhabditis elegans Brap2 ortholog (BRAP-2) and found that it is required to prevent larval arrest in response to elevated levels of oxidative stress. Here, we report that C. elegans brap-2 mutants display increased expression of SKN-1-dependent, phase II detoxification enzymes that is dependent on PMK-1 (a p38 MAPK C. elegans ortholog). An RNA-interference screen was conducted using a transcription factor library to identify genes required for increased expression of the SKN-1 target gst-4 in brap-2 mutants...
August 2017: Genetics
https://www.readbyqxmd.com/read/28431244/bacterial-metabolism-affects-the-c-%C3%A2-elegans-response-to-cancer-chemotherapeutics
#5
Aurian P García-González, Ashlyn D Ritter, Shaleen Shrestha, Erik C Andersen, L Safak Yilmaz, Albertha J M Walhout
The human microbiota greatly affects physiology and disease; however, the contribution of bacteria to the response to chemotherapeutic drugs remains poorly understood. Caenorhabditis elegans and its bacterial diet provide a powerful system to study host-bacteria interactions. Here, we use this system to study how bacteria affect the C. elegans response to chemotherapeutics. We find that different bacterial species can increase the response to one drug yet decrease the effect of another. We perform genetic screens in two bacterial species using three chemotherapeutic drugs: 5-fluorouracil (5-FU), 5-fluoro-2'-deoxyuridine (FUDR), and camptothecin (CPT)...
April 20, 2017: Cell
https://www.readbyqxmd.com/read/28189107/c-elegans-and-its-bacterial-diet-as-a-model-for-systems-level-understanding-of-host-microbiota-interactions
#6
REVIEW
Jingyan Zhang, Amy D Holdorf, Albertha Jm Walhout
Resident microbes of the human body, particularly the gut microbiota, provide essential functions for the host, and, therefore, have important roles in human health as well as mitigating disease. It is difficult to study the mechanisms by which the microbiota affect human health, especially at a systems-level, due to heterogeneity of human genomes, the complexity and heterogeneity of the gut microbiota, the challenge of growing these bacteria in the laboratory, and the lack of bacterial genetics in most microbiotal species...
August 2017: Current Opinion in Biotechnology
https://www.readbyqxmd.com/read/28088694/metabolic-network-modeling-with-model-organisms
#7
REVIEW
L Safak Yilmaz, Albertha Jm Walhout
Flux balance analysis (FBA) with genome-scale metabolic network models (GSMNM) allows systems level predictions of metabolism in a variety of organisms. Different types of predictions with different accuracy levels can be made depending on the applied experimental constraints ranging from measurement of exchange fluxes to the integration of gene expression data. Metabolic network modeling with model organisms has pioneered method development in this field. In addition, model organism GSMNMs are useful for basic understanding of metabolism, and in the case of animal models, for the study of metabolic human diseases...
February 2017: Current Opinion in Chemical Biology
https://www.readbyqxmd.com/read/27934693/gene-centered-yeast-one-hybrid-assays
#8
Juan I Fuxman Bass, John S Reece-Hoyes, Albertha J M Walhout
An important question when studying gene regulation is which transcription factors (TFs) interact with which cis-regulatory elements, such as promoters and enhancers. Addressing this issue in complex multicellular organisms is challenging as several hundreds of TFs and thousands of regulatory elements must be considered in the context of different tissues and physiological conditions. Yeast one-hybrid (Y1H) assays provide a powerful "gene-centered" method to identify the TFs that can bind a DNA sequence of interest...
December 1, 2016: Cold Spring Harbor Protocols
https://www.readbyqxmd.com/read/27934686/zymolyase-treatment-and-polymerase-chain-reaction-amplification-from-genomic-and-plasmid-templates-from-yeast
#9
Juan I Fuxman Bass, John S Reece-Hoyes, Albertha J M Walhout
Here, we present a protocol for amplifying DNA fragments from the genome of, or plasmids transformed into, yeast strains that require the use of the lytic enzyme zymolyase to break open the yeast cells by digesting the cell wall. Yeast strains requiring such treatment include YM4271 and Y1HaS2, whereas other yeast strains (e.g., MaV103) might not require treatment with Zymolyase.
December 1, 2016: Cold Spring Harbor Protocols
https://www.readbyqxmd.com/read/27934685/colony-lift-colorimetric-assay-for-%C3%AE-galactosidase-activity
#10
Juan I Fuxman Bass, John S Reece-Hoyes, Albertha J M Walhout
In this protocol, we present a qualitative assay for monitoring the level of expression of β-galactosidase, an enzyme encoded by the LacZ gene, in yeast. This is useful both for determining autoactivity of LacZ expression in yeast DNA "bait" strains and for assessing LacZ reporter gene activation mediated by a transcription factor "prey" interaction with a DNA bait of interest in yeast one-hybrid (Y1H) assays. In this colorimetric assay, yeast are lysed in liquid nitrogen and then assayed for β-galactosidase expression using the colorless compound X-gal, which turns blue in the presence of this enzyme...
December 1, 2016: Cold Spring Harbor Protocols
https://www.readbyqxmd.com/read/27934684/performing-yeast-one-hybrid-library-screens
#11
Juan I Fuxman Bass, John S Reece-Hoyes, Albertha J M Walhout
Yeast one-hybrid (Y1H) assays are used to identify which transcription factor (TF) "prey" molecules can bind a DNA fragment of interest that is used as "bait". Y1H assays involve introducing plasmids that encode TFs into a yeast "bait strain" in which the DNA fragment of interest is integrated upstream of one or more reporters, and activation of these reporters indicates that a TF-DNA interaction has occurred. These plasmids express each TF as a hybrid protein (hence the "one-hybrid" name) fused to the activation domain (AD) of the yeast TF Gal4...
December 1, 2016: Cold Spring Harbor Protocols
https://www.readbyqxmd.com/read/27934683/generating-bait-strains-for-yeast-one-hybrid-assays
#12
Juan I Fuxman Bass, John S Reece-Hoyes, Albertha J M Walhout
Yeast one-hybrid (Y1H) assays are used to identify which transcription factor (TF) "preys" can bind a DNA fragment of interest that is used as the "bait." Undertaking Y1H assays requires the generation of a yeast "bait strain" for each DNA fragment of interest that features the DNA bait coupled to a reporter(s). Plasmids encoding TFs fused to the Gal4 activation domain (AD) are then introduced into the bait strain, and activation of the reporter(s) indicates that a TF-DNA interaction has occurred. Here, we present a protocol for the first part of the strategy-the generation of a bait strain for Y1H assays...
December 1, 2016: Cold Spring Harbor Protocols
https://www.readbyqxmd.com/read/27777270/a-gene-centered-c-%C3%A2-elegans-protein-dna-interaction-network-provides-a-framework-for-functional-predictions
#13
Juan I Fuxman Bass, Carles Pons, Lucie Kozlowski, John S Reece-Hoyes, Shaleen Shrestha, Amy D Holdorf, Akihiro Mori, Chad L Myers, Albertha Jm Walhout
Transcription factors (TFs) play a central role in controlling spatiotemporal gene expression and the response to environmental cues. A comprehensive understanding of gene regulation requires integrating physical protein-DNA interactions (PDIs) with TF regulatory activity, expression patterns, and phenotypic data. Although great progress has been made in mapping PDIs using chromatin immunoprecipitation, these studies have only characterized ~10% of TFs in any metazoan species. The nematode C. elegans has been widely used to study gene regulation due to its compact genome with short regulatory sequences...
October 24, 2016: Molecular Systems Biology
https://www.readbyqxmd.com/read/27756805/widespread-structural-brain-involvement-in-als-is-not-limited-to-the-c9orf72-repeat-expansion
#14
Henk-Jan Westeneng, Renée Walhout, Milou Straathof, Ruben Schmidt, Jeroen Hendrikse, Jan H Veldink, Martijn P van den Heuvel, Leonard H van den Berg
BACKGROUND: In patients with a C9orf72 repeat expansion (C9+), a neuroimaging phenotype with widespread structural cerebral changes has been found. We aimed to investigate the specificity of this neuroimaging phenotype in patients with amyotrophic lateral sclerosis (ALS). METHODS: 156 C9- and 14 C9+ patients with ALS underwent high-resolution T1-weighted MRI; a subset (n=126) underwent diffusion-weighted imaging. Cortical thickness, subcortical volumes and white matter integrity were compared between C9+ and C9- patients...
December 2016: Journal of Neurology, Neurosurgery, and Psychiatry
https://www.readbyqxmd.com/read/27383050/metabolic-network-rewiring-of-propionate-flux-compensates-vitamin-b12-deficiency-in-c-elegans
#15
Emma Watson, Viridiana Olin-Sandoval, Michael J Hoy, Chi-Hua Li, Timo Louisse, Victoria Yao, Akihiro Mori, Amy D Holdorf, Olga G Troyanskaya, Markus Ralser, Albertha Jm Walhout
Metabolic network rewiring is the rerouting of metabolism through the use of alternate enzymes to adjust pathway flux and accomplish specific anabolic or catabolic objectives. Here, we report the first characterization of two parallel pathways for the breakdown of the short chain fatty acid propionate in Caenorhabditis elegans. Using genetic interaction mapping, gene co-expression analysis, pathway intermediate quantification and carbon tracing, we uncover a vitamin B12-independent propionate breakdown shunt that is transcriptionally activated on vitamin B12 deficient diets, or under genetic conditions mimicking the human diseases propionic- and methylmalonic acidemia, in which the canonical B12-dependent propionate breakdown pathway is blocked...
2016: ELife
https://www.readbyqxmd.com/read/27227390/scanning-tunneling-spectroscopy-study-of-the-dirac-spectrum-of-germanene
#16
C J Walhout, A Acun, L Zhang, M Ezawa, H J W Zandvliet
The temperature dependence of the density of states of germanene, synthesized on Ge/Pt crystals, has been investigated with scanning tunneling spectroscopy. After correction for thermal broadening, a virtually perfect V-shaped density of states, which is a hallmark of a two-dimensional Dirac system, has been found. In an attempt to directly measure the energy dispersion relation via quasiparticle interference we have recorded spatial maps of the differential conductivity near the edges and defects of germanene...
July 20, 2016: Journal of Physics. Condensed Matter: An Institute of Physics Journal
https://www.readbyqxmd.com/read/27211857/a-caenorhabditis-elegans-genome-scale-metabolic-network-model
#17
L Safak Yilmaz, Albertha J M Walhout
Caenorhabditis elegans is a powerful model to study metabolism and how it relates to nutrition, gene expression, and life history traits. However, while numerous experimental techniques that enable perturbation of its diet and gene function are available, a high-quality metabolic network model has been lacking. Here, we reconstruct an initial version of the C. elegans metabolic network. This network model contains 1,273 genes, 623 enzymes, and 1,985 metabolic reactions and is referred to as iCEL1273. Using flux balance analysis, we show that iCEL1273 is capable of representing the conversion of bacterial biomass into C...
May 25, 2016: Cell Systems
https://www.readbyqxmd.com/read/27127907/intramolecular-hydrogen-bonding-effects-on-the-fluorescence-of-prodan-derivatives
#18
Isaac G Alty, Douglas W Cheek, Tao Chen, David B Smith, Emma Q Walhout, Christopher J Abelt
The effects of intramolecular hydrogen-bonding on the fluorescence behavior of three derivatives of 6-propionyl-2-dimethylaminonaphthalene are reported. The H-bonding effects are revealed through comparisons with corresponding reference compounds in which the H-bond-donating hydroxyl groups are replaced with methoxy groups. In toluene, intramolecular H bonding gives rise to a dramatic increase in the fluorescence intensity but only a slight red shift in the position. This behavior is attributed to decreased efficiency in intersystem crossing due to an increase in the energy of the n → π* triplet state...
May 26, 2016: Journal of Physical Chemistry. A
https://www.readbyqxmd.com/read/26631516/understanding-metabolic-regulation-at-a-systems-level-metabolite-sensing-mathematical-predictions-and-model-organisms
#19
REVIEW
Emma Watson, L Safak Yilmaz, Albertha J M Walhout
Metabolic networks are extensively regulated to facilitate tissue-specific metabolic programs and robustly maintain homeostasis in response to dietary changes. Homeostatic metabolic regulation is achieved through metabolite sensing coupled to feedback regulation of metabolic enzyme activity or expression. With a wealth of transcriptomic, proteomic, and metabolomic data available for different cell types across various conditions, we are challenged with understanding global metabolic network regulation and the resulting metabolic outputs...
2015: Annual Review of Genetics
https://www.readbyqxmd.com/read/25910213/human-gene-centered-transcription-factor-networks-for-enhancers-and-disease-variants
#20
Juan I Fuxman Bass, Nidhi Sahni, Shaleen Shrestha, Aurian Garcia-Gonzalez, Akihiro Mori, Numana Bhat, Song Yi, David E Hill, Marc Vidal, Albertha J M Walhout
Gene regulatory networks (GRNs) comprising interactions between transcription factors (TFs) and regulatory loci control development and physiology. Numerous disease-associated mutations have been identified, the vast majority residing in non-coding regions of the genome. As current GRN mapping methods test one TF at a time and require the use of cells harboring the mutation(s) of interest, they are not suitable to identify TFs that bind to wild-type and mutant loci. Here, we use gene-centered yeast one-hybrid (eY1H) assays to interrogate binding of 1,086 human TFs to 246 enhancers, as well as to 109 non-coding disease mutations...
April 23, 2015: Cell
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