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https://www.readbyqxmd.com/read/28319812/exploring-sequence-space-harnessing-chemical-and-biological-diversity-towards-new-peptide-leads
#1
REVIEW
Richard Obexer, Louise J Walport, Hiroaki Suga
From their early roots in natural products, peptides now represent an expanding class of novel drugs. Their modular structures make them ideal candidates for pooled library screening approaches. Key technologies for library generation and screening, such as SICLOPPS, phage display and mRNA display, give unparalleled access to tight binding peptides. Through combination with genetic code reprogramming and chemical modifications, access to more natural product-like libraries, spanning non-canonical peptide space, is readily achievable...
March 17, 2017: Current Opinion in Chemical Biology
https://www.readbyqxmd.com/read/28319736/structural-variants-in-snca-gene-and-the-implication-to-synucleinopathies
#2
REVIEW
Ornit Chiba-Falek
Synucleinopathies are a group of neurodegenerative diseases that share a common pathological lesion of intracellular protein inclusions largely composed of aggregates of alpha-synuclein protein. Accumulating evidence, including genome-wide association studies, has implicated the alpha-synuclein (SNCA) gene in the etiology of synucleinopathies and it has been suggested that SNCA expression levels are critical for the development of these diseases. This review focuses on genetic variants from the class of structural variants (SVs), including multiplication of large genomic segments and short (<50bp) genomic variants such as simple sequence repeats (SSRs), within the SNCA locus...
March 2, 2017: Current Opinion in Genetics & Development
https://www.readbyqxmd.com/read/28319100/metagenomic-discovery-of-polybrominated-diphenyl-ether-biosynthesis-by-marine-sponges
#3
Vinayak Agarwal, Jessica M Blanton, Sheila Podell, Arnaud Taton, Michelle A Schorn, Julia Busch, Zhenjian Lin, Eric W Schmidt, Paul R Jensen, Valerie J Paul, Jason S Biggs, James W Golden, Eric E Allen, Bradley S Moore
Naturally produced polybrominated diphenyl ethers (PBDEs) pervade the marine environment and structurally resemble toxic man-made brominated flame retardants. PBDEs bioaccumulate in marine animals and are likely transferred to the human food chain. However, the biogenic basis for PBDE production in one of their most prolific sources, marine sponges of the order Dysideidae, remains unidentified. Here, we report the discovery of PBDE biosynthetic gene clusters within sponge-microbiome-associated cyanobacterial endosymbionts through the use of an unbiased metagenome-mining approach...
March 20, 2017: Nature Chemical Biology
https://www.readbyqxmd.com/read/28319062/ctcf-genetic-alterations-in-endometrial-carcinoma-are-pro-tumorigenic
#4
A D Marshall, C G Bailey, K Champ, M Vellozzi, P O'Young, C Metierre, Y Feng, A Thoeng, A M Richards, U Schmitz, M Biro, R Jayasinghe, L Ding, L Anderson, E R Mardis, J E J Rasko
CTCF is a haploinsufficient tumour suppressor gene with diverse normal functions in genome structure and gene regulation. However the mechanism by which CTCF haploinsufficiency contributes to cancer development is not well understood. CTCF is frequently mutated in endometrial cancer. Here we show that most CTCF mutations effectively result in CTCF haploinsufficiency through nonsense-mediated decay of mutant transcripts, or loss-of-function missense mutation. Conversely, we identified a recurrent CTCF mutation K365T, which alters a DNA binding residue, and acts as a gain-of-function mutation enhancing cell survival...
March 20, 2017: Oncogene
https://www.readbyqxmd.com/read/28318784/kinetics-of-endogenous-camkii-required-for-synaptic-plasticity-revealed-by-optogenetic-kinase-inhibitor
#5
Hideji Murakoshi, Myung Eun Shin, Paula Parra-Bueno, Erzsebet M Szatmari, Akihiro C E Shibata, Ryohei Yasuda
Elucidating temporal windows of signaling activity required for synaptic and behavioral plasticity is crucial for understanding molecular mechanisms underlying these phenomena. Here, we developed photoactivatable autocamtide inhibitory peptide 2 (paAIP2), a genetically encoded, light-inducible inhibitor of CaMKII activity. The photoactivation of paAIP2 in neurons for 1-2 min during the induction of LTP and structural LTP (sLTP) of dendritic spines inhibited these forms of plasticity in hippocampal slices of rodents...
March 8, 2017: Neuron
https://www.readbyqxmd.com/read/28318778/stenotrophomonas-maltophilia-healthcare-associated-infections-identification-of-two-main-pathogenic-genetic-backgrounds
#6
C Corlouer, B Lamy, M Desroches, J Ramos-Vivas, E Mehiri-Zghal, O Lemenand, J-M Delarbre, J-W Decousser
BACKGROUND: Stenotrophomonas maltophilia is an opportunistic multi-drug-resistant bacterium responsible for healthcare-associated infections. Strategies for in-hospital infection control and management of carriers and environmental reservoirs remain controversial. AIM: To determine the population structure of S. maltophilia strains in hospitalized infected patients and to identify putative highly pathogenic subpopulations that require upgraded infection control measures...
February 9, 2017: Journal of Hospital Infection
https://www.readbyqxmd.com/read/28317975/exposing-the-g-quadruplex-to-electric-fields-the-role-played-by-telomeres-in-the-propagation-of-dna-errors
#7
José Pedro Cerón-Carrasco, Denis Jacquemin
To protect their core machinery from the attack of exogenous agents, cells locate DNA in their nucleus. Nevertheless, some reactive chemical species and physical agents might reach DNA and alter its natural double helix structure. For instance, pulsed electric fields can be used to selectively rewrite the stored genetic information. However, for such modification to be effective, one needs, as a prerequisite, that the replication mechanism is not stopped by the field, so that the changes propagate over the following generations...
March 20, 2017: Physical Chemistry Chemical Physics: PCCP
https://www.readbyqxmd.com/read/28316324/spatial-organization-of-dna-sequences-directs-the-assembly-of-bacterial-chromatin-by-a-nucleoid-associated-protein
#8
Aleksandre Japarize, Sylvain Renevey, Parick Sobetzko, Liubov Stoliar, William Nasser, Giovanni Dietler, Georgi Muskhelishvili
Structural differentiation of bacterial chromatin depends on cooperative binding of abundant nucleoid-associated proteins at numerous genomic DNA sites and stabilization of distinct long-range nucleoprotein structures. Histone-like nucleoid-structuring protein (H-NS) is an abundant DNA-bridging, nucleoid-associated protein that binds to an AT rich conserved DNA sequence motif and regulates both the shape and the genetic expression of the bacterial chromosome. Although there is ample evidence that the mode of H-NS binding depends on environmental conditions, the role of the spatial organization of H-NS binding sequences in the assembly of long-range nucleoprotein structures remains unknown...
March 18, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28316285/discipline-building-in-germany-women-and-genetics-at-the-berlin-institute-for-heredity-research
#9
Ida H Stamhuis, Annette B Vogt
The origin and the development of scientific disciplines has been a topic of reflection for several decades. The few extensive case studies support the thesis that scientific disciplines are not monolithic structures but can be characterized by distinct social, organizational and scientific-technical practices. Nonetheless, most disciplinary histories of genetics confine themselves largely to an uncontested account of the content of the discipline or occasionally institutional factors. Little attention is paid to the large number of researchers who, by their joint efforts, ultimately shaped the discipline...
March 20, 2017: British Journal for the History of Science
https://www.readbyqxmd.com/read/28316119/animal-tracking-meets-migration-genomics-transcriptomic-analysis-of-a-partially-migratory-bird-species
#10
Paolo Franchini, Iker Irisarri, Adam Fudickar, Andreas Schmidt, Axel Meyer, Martin Wikelski, Jesko Partecke
Seasonal migration is a widespread phenomenon, which is found in many different lineages of animals. This spectacular behaviour allows animals to avoid seasonally adverse environmental conditions to exploit more favourable habitats. Migration has been intensively studied in birds, which display astonishing variation in migration strategies, thus providing a powerful system for studying the ecological and evolutionary processes that shape migratory behaviour. Despite intensive research, the genetic basis of migration remains largely unknown...
March 17, 2017: Molecular Ecology
https://www.readbyqxmd.com/read/28316108/cry1a-b-16-toxin-from-bacillus-thuringiensis-theoretical-refinement-of-three-dimensional-structure-and-prediction-of-peptides-as-molecular-markers-for-detection-of-genetically-modified-organisms
#11
Alexandra Plácido, Andreia Coelho, Lucas Abreu do Nascimento, Andreanne Gomes Vasconcelos, Maria Fátima Barroso, Joilson Ramos-Jesus, Vladimir Costa, Francisco das Chagas Alves Lima, Cristina Delerue-Matos, Ricardo Martins Ramos, Mariela M Marani, José Roberto de Souza de Almeida Leite
Transgenic maize produced by the insertion of the Cry transgene into its genome became the second most cultivated crop worldwide. Cry gene from Bacillus thuringiensis kurstaki expresses protein derivatives of crystalline endotoxins which confer insect resistance onto the maize crop. Mandatory labeling of processed food containing or made by genetically modified organisms is in force in many countries, so, it is very urgent to develop fast and practical methods for GMO identification, e.g., biosensors. In the absence of an available empirical structure of Cry1A(b)16 protein, a theoretical model was effectively generated, in this work, by homology modeling and molecular dynamics simulations based on two available homologous protein structures...
March 18, 2017: Proteins
https://www.readbyqxmd.com/read/28315830/paternal-induction-of-hybrid-dysgenesis-in-drosophila-melanogaster-is-weakly-correlated-with-both-p-element-and-hobo-element-dosage
#12
Satyam P Srivastav, Erin S Kelleher
Transposable elements (TEs) are virtually ubiquitous components of genomes, yet they often impose significant fitness consequences on their hosts. In addition to producing specific deleterious mutations by insertional inactivation, TEs also impose general fitness costs by inducing DNA damage and participating in ectopic recombination. These latter fitness costs are often assumed to be dosage-dependent, with stronger effects occurring in the presence of higher TE copy numbers. We test this assumption in Drosophila melanogaster by considering the relationship between the copy number of two active DNA transposons, P-element and hobo element, and the incidence of hybrid dysgenesis, a sterility syndrome associated with transposon activity in the germline...
March 17, 2017: G3: Genes—Genomes—Genetics
https://www.readbyqxmd.com/read/28315813/the-case-for-applying-tissue-engineering-methodologies-to-instruct-human-organoid-morphogenesis
#13
REVIEW
Carlos R Marti-Figueroa, Randolph S Ashton
Three-dimensional organoids derived from human pluripotent stem cell (hPSC) derivatives have become widely used in vitro models for studying development and disease. Their ability to recapitulate facets of normal human development during in vitro morphogenesis produces tissue structures with unprecedented biomimicry. Current organoid derivation protocols primarily rely on spontaneous morphogenesis processes to occur within 3-D spherical cell aggregates with minimal to no exogenous control. This yields organoids containing microscale regions of biomimetic tissues, but at the macroscale (i...
March 15, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/28315745/production-of-low-expressing-recombinant-cationic-biopolymers-with-high-purity
#14
Xuguang Chen, Alireza Nomani, Niket Patel, Arash Hatefi
The growing complexity of recombinant biopolymers for delivery of bioactive agents requires the ability to control the biomaterial structure with high degree of precision. Genetic engineering techniques have provided this opportunity to synthesize biomaterials in an organism such as E. coli with full control over their lengths and sequences. One class of such biopolymers is recombinant cationic biopolymers with applications in gene delivery, regenerative medicine and variety of other biomedical applications...
March 15, 2017: Protein Expression and Purification
https://www.readbyqxmd.com/read/28315422/sfpq-psf-tfe3-renal-cell-carcinoma-rcc-a-clinicopathologic-study-emphasizing-extended-morphology-and-reviewing-the-differences-between-sfpq-tfe3-rcc-and-the-corresponding-mesenchymal-neoplasm-despite-an-identical-gene-fusion
#15
Xiao-Tong Wang, Qiu-Yuan Xia, Hao Ni, Sheng-Bing Ye, Rui Li, Xuan Wang, Shan-Shan Shi, Xiao-Jun Zhou, Qiu Rao
Xp11 translocation renal cell carcinoma (RCC) with SFPQ/PSF-TFE3 gene fusion is a rare epithelial tumor. Of note, the appearance of the gene fusion does not necessarily mean that it is renal cell carcinoma. The corresponding mesenchymal neoplasms, including Xp11 neoplasm with melanocytic differentiation, TFE3 rearrangement-associated perivascular epithelioid cell tumor (PEComa) and melanotic Xp11 translocation renal cancer, can also harbor the identical gene fusion. However, the differences between Xp11 translocation RCC and the corresponding mesenchymal neoplasm have only recently been described...
March 14, 2017: Human Pathology
https://www.readbyqxmd.com/read/28315412/engineering-bacterial-translation-initiation-do-we-have-all-the-tools-we-need
#16
REVIEW
Justin Vigar, Hans-Joachim Wieden
BACKGROUND: Reliable tools that allow precise and predictable control over gene expression are critical for the success of nearly all bioengineering applications. Translation initiation is the most regulated phase during protein biosynthesis, and is therefore a promising target for exerting control over gene expression. At the translational level, the copy number of a protein can be fine-tuned by altering the interaction between the translation initiation region of an mRNA and the ribosome...
March 14, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28315021/clinical-strains-of-streptococcus-agalactiae-carry-two-different-variants-of-pathogenicity-island-xii
#17
Eugenia Kuleshevich, Joseph Ferretti, Ilda Santos Sanches, Natesan Balasubramanian, Barbara Spellerberg, Androulla Efstratiou, Paula Kriz, Kornelia Grabovskaya, Olga Arjanova, Alevtina Savitcheva, Valentin Shevchenko, Anton Rysev, Alexander Suvorov
Streptococcus agalactiae or Group B streptococci (GBS) are a common cause of serious diseases of newborns and adults. GBS pathogenicity largely depends on genes located on the accessory genome including several pathogenicity islands (PAI). The present paper is focused on the structure and molecular epidemiological analysis of one of the GBS pathogenicity islands-the pathogenicity island PAI XII (Glaser et al. Mol Microbiol 45(6):1499-1513, 2002). This PAI was found to be composed of three different mobile genetic elements: a composite transposon (PAI-C), a genomic islet (PAI-B), and a pathogenicity island associated with gene sspB1 (PAI-A)...
March 18, 2017: Folia Microbiologica
https://www.readbyqxmd.com/read/28314934/transposon-insertion-resulted-in-the-silencing-of-wx-b1n-in-chinese-wheat-landraces
#18
Ling-Ling Zhang, Hu Chen, Mi Luo, Xiao-Wei Zhang, Mei Deng, Jian Ma, Peng-Fei Qi, Ji-Rui Wang, Guo-Yue Chen, Ya-Xi Liu, Zhi-En Pu, Wei Li, Xiu-Jin Lan, Yu-Ming Wei, You-Liang Zheng, Qian-Tao Jiang
A novel Wx-B1 allele was characterized; a transposon insertion resulted in the loss of its function, which is different from the previously reported gene silencing mechanisms at the Wx-B1 locus. The waxy protein composition of 53 Chinese wheat landraces was analyzed using sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and two-dimensional gel electrophoresis; of these, 10 did not show the expression of Wx-A1 (four accession) or Wx-B1 (six accessions) protein. The results of molecular marker detection revealed that the Wx-B1 allele (Wx-B1n) showed normal expression, inconsistent with the findings of SDS-PAGE for the Xiaobaipi accession...
March 17, 2017: TAG. Theoretical and Applied Genetics. Theoretische und Angewandte Genetik
https://www.readbyqxmd.com/read/28314870/perillyl-alcohol-a-pleiotropic-natural-compound-suitable-for-brain-tumor-therapy-targets-free-radicals
#19
REVIEW
Aline C Gomes, Angélica L Mello, Manuel G Ribeiro, Diogo G Garcia, Clovis O Da Fonseca, Marcela D'Alincourt Salazar, Axel H Schönthal, Thereza Quirico-Santos
Monoterpenes such as limonene and perillyl alcohol (POH) are promising natural compounds with pro-oxidant properties partly due to endoplasmic reticulum (ER) stress-induced cytotoxicity, and antioxidant activity owing to their activity as free radical scavengers, inhibition of coenzyme Q synthesis, activation of antioxidant-responsive elements (inducing detoxification enzymes) and induction of apoptosis. Activation of ER-stress responses generates reactive oxygen species (ROS), which are highly reactive free radicals mainly produced during mitochondrial electron transfer for adenosine triphosphate (ATP) synthesis...
March 17, 2017: Archivum Immunologiae et Therapiae Experimentalis
https://www.readbyqxmd.com/read/28314413/recent-progress-in-the-discovery-and-development-of-trpa1-modulators
#20
S Skerratt
TRPA1 is a well-validated therapeutic target in areas of high unmet medical need that include pain and respiratory disorders. The human genetic rationale for TRPA1 as a pain target is provided by a study describing a rare gain-of-function mutation in TRPA1, causing familial episodic pain syndrome. There is a growing interest in the TRPA1 field, with many pharmaceutical companies reporting the discovery of TRPA1 chemical matter; however, GRC 17536 remains to date the only TRPA1 antagonist to have completed Phase IIa studies...
2017: Progress in Medicinal Chemistry
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