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On and Off Pathways

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https://www.readbyqxmd.com/read/28630151/assembly-mechanism-of-the-%C3%AE-pore-forming-toxin-cytolysin-a-from-escherichia-coli
#1
REVIEW
Daniel Roderer, Rudi Glockshuber
The cytolytic toxin cytolysin A (ClyA) from Escherichia coli is probably one of the best-characterized examples of bacterial, α-pore-forming toxins (α-PFTs). Like other PFTs, ClyA exists in a soluble, monomeric form that assembles to an annular, homo-oligomeric pore complex upon contact with detergent or target membranes. Comparison of the three-dimensional structures of the 34 kDa monomer and the protomer in the context of the dodecameric pore complex revealed that ClyA undergoes one of the largest conformational transitions described for proteins so far, in which 55% of the residues change their position and 16% of the residues adopt a different secondary structure in the protomer...
August 5, 2017: Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
https://www.readbyqxmd.com/read/28625564/crispr-system-in-filamentous-fungi-current-achievements-and-future-directions
#2
REVIEW
Huaxiang Deng, Ruijie Gao, Xiangru Liao, Yujie Cai
As eukaryotes, filamentous fungi share many features with humans, and they produce numerous active metabolites, some of which are toxic. Traditional genetic approaches are generally inefficient, but the clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 system that has been widely used for basic research on bacteria, mammals and plants offers a simple, fast, versatile technology for systemic research on filamentous fungi. In this review, we summarized the current knowledge on Cas9 and its variants, different ways used to detect off-target, and different approaches used to express and transform the CRISPR complex...
June 15, 2017: Gene
https://www.readbyqxmd.com/read/28623188/gli1-induced-deubiquitinase-usp48-aids-glioblastoma-tumorigenesis-by-stabilizing-gli1
#3
Aidong Zhou, Kangyu Lin, Sicong Zhang, Li Ma, Jianfei Xue, Saint-Aaron Morris, Kenneth D Aldape, Suyun Huang
Aberrant activation of the Hedgehog (Hh) signaling pathway drives the tumorigenesis of multiple cancers. In this study, we screened a panel of deubiquitinases that may regulate the Hh pathway. We find that deubiquitinase USP48 activates Gli-dependent transcription by stabilizing Gli1 protein. Mechanistically, USP48 interacts with Gli1 and cleaves its ubiquitin off directly. In glioblastoma cells, knockdown of USP48 inhibits cell proliferation and the expression of Gli1's downstream targets, which leads to repressed glioblastoma tumorigenesis...
June 16, 2017: EMBO Reports
https://www.readbyqxmd.com/read/28620897/enhanced-recovery-pathway-in-elderly-patients-undergoing-colorectal-surgery-is-there-an-effect-of-increasing-ages-results-from-the-perioperative-italian-society-registry
#4
Marco Braga, Luigi Beretta, Nicolò Pecorelli, Marianna Maspero, Umberto Casiraghi, Felice Borghi, Luca Pellegrino, Stefano Bona, Roberta Monzani, Gianluigi Ferrari, Danilo Radrizzani, Riccardo Iuliani, Carlo Bima, Marco Scatizzi, Giancarlo Missana, Marco Azzola Guicciardi, Andrea Muratore, Michele Crespi, Hedayat Bouzari, Andrea Pisani Ceretti, Ferdinando Ficari
Previous studies reported that enhanced recovery pathway (ERP) is safe in elderly who did not require a specifically tailored protocol. In previous studies, elderly have been considered as a homogeneous cohort and the cut-off value to identify them was different. The aim of the present study is to assess the compliance to ERP and its impact on postoperative outcome in three subgroups of elderly patients with increasing ages. Prospectively collected data entered in an electronic Italian registry specifically designed for ERP were reviewed...
June 15, 2017: Updates in Surgery
https://www.readbyqxmd.com/read/28620044/let-there-be-light-how-to-use-photoswitchable-cross-linker-to-reprogram-proteins
#5
REVIEW
Daniel Hoersch
Azobenzene is a photo-isomerizing molecule whose end-to-end distance changes upon external illumination. When combined with site-specific reactive groups, it can be used as molecular tweezers to remote-control the structure and function of protein targets. The present study gives a brief overview over the rational design strategies that use an azobenzene-based photoswitchable cross-linker to engineer ON/OFF switches into functional proteins or to reprogram proteins for novel functions. The re-engineered proteins may be used as remote controls for cellular pathways, as light-gated drug delivery platforms or as light-powered machinery of synthetic cells and micro-scaled factories...
June 15, 2017: Biochemical Society Transactions
https://www.readbyqxmd.com/read/28617863/the-use-of-metabolic-profiling-to-identify-insulin-resistance-in-veal-calves
#6
Andre J Pantophlet, Han Roelofsen, Marcel P de Vries, Walter J J Gerrits, Joost J G C van den Borne, Roel J Vonk
Heavy veal calves (4-6 months old) are at risk of developing insulin resistance and disturbed glucose homeostasis. Prolonged insulin resistance could lead to metabolic disorders and impaired growth performance. Recently, we discovered that heavy Holstein-Friesian calves raised on a high-lactose or high-fat diet did not differ in insulin sensitivity, that insulin sensitivity was low and 50% of the calves could be considered insulin resistant. Understanding the patho-physiological mechanisms underlying insulin resistance and discovering biomarkers for early diagnosis would be useful for developing prevention strategies...
2017: PloS One
https://www.readbyqxmd.com/read/28616764/abrupt-salinity-stress-induces-oxidative-stress-via-the-nrf2-keap1-signaling-pathway-in-large-yellow-croaker-pseudosciaena-crocea
#7
Lin Zeng, Chun-Xiang Ai, Yong-Hong Wang, Jian-She Zhang, Chang-Wen Wu
The aim of the present study was to evaluate the effects of abrupt salinity stress (12, 26 (control), and 40) on lipid peroxidation, activities and mRNA levels of antioxidant enzymes (Cu/Zn-SOD, CAT, GPx, and GR), and gene expression of the Nrf2-Keap1 signaling molecules at different times (6, 12, 24, and 48 h) in the liver of large yellow croaker Pseudosciaena crocea. The results showed that lipid peroxidation was sharply reduced at 6 h and increased at 12 h before returning to control levels in the hypo-salinity group...
June 14, 2017: Fish Physiology and Biochemistry
https://www.readbyqxmd.com/read/28611595/mtorc1-is-a-local-postsynaptic-voltage-sensor-regulated-by-positive-and-negative-feedback-pathways
#8
Farr Niere, Kimberly F Raab-Graham
The mammalian/mechanistic target of rapamycin complex 1 (mTORC1) serves as a regulator of mRNA translation. Recent studies suggest that mTORC1 may also serve as a local, voltage sensor in the postsynaptic region of neurons. Considering biochemical, bioinformatics and imaging data, we hypothesize that the activity state of mTORC1 dynamically regulates local membrane potential by promoting and repressing protein synthesis of select mRNAs. Our hypothesis suggests that mTORC1 uses positive and negative feedback pathways, in a branch-specific manner, to maintain neuronal excitability within an optimal range...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28605593/simultaneous-drug-targeting-of-the-promoter-myc-g-quadruplex-and-bcl2-i-motif-in-diffuse-large-b-cell-lymphoma-delays-tumor-growth
#9
Samantha Kendrick, Andrea Muranyi, Vijay Gokhale, Laurence H Hurley, Lisa M Rimsza
Secondary DNA structures are uniquely poised as therapeutic targets due to their molecular switch function in turning gene expression on or off and scaffold-like properties for protein and small molecule interaction. Strategies to alter gene transcription through these structures thus far involve targeting single DNA conformations. Here we investigate the feasibility of simultaneously targeting different secondary DNA structures to modulate two key oncogenes, cellular-myelocytomatosis (MYC) and B-cell lymphoma gene-2 (BCL2), in diffuse large B-cell lymphoma (DLBCL)...
June 12, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28605052/effects-of-pedunculopontine-nucleus-stimulation-on-human-bladder-function
#10
Holly A Roy, Debbie Pond, Christopher Roy, Beth Forrow, Thomas Foltynie, Ludvic Zrinzo, Harith Akram, Tipu Z Aziz, James J FitzGerald, Alexander L Green
AIMS: The pedunculopontine nucleus (PPN) is a deep brain stimulation target for Parkinson's disease (PD). Unilateral PPN stimulation has been described in a previous case report to provoke urinary frequency, urgency and detrusor overactivity, due to probable activation of the pontine micturition center. Our aim was to evaluate the effect of bilateral PPN DBS on urodynamic parameters and to investigate the likely mechanisms using probabilistic tractography. METHODS: Six male PD subjects with bilateral PPN deep brain stimulators were recruited...
June 12, 2017: Neurourology and Urodynamics
https://www.readbyqxmd.com/read/28603537/flowering-locus-c-flc-is-a-potential-major-regulator-of-glucosinolate-content-across-developmental-stages-of-aethionema-arabicum-brassicaceae
#11
Setareh Mohammadin, Thu-Phuong Nguyen, Marco S van Weij, Michael Reichelt, Michael E Schranz
The biochemical defense of plants can change during their life-cycle and impact herbivore feeding and plant fitness. The annual species Aethionema arabicum is part of the sister clade to all other Brassicaceae. Hence, it holds a phylogenetically important position for studying crucifer trait evolution. Glucosinolates (GS) are essentially Brassicales-specific metabolites involved in plant defense. Using two Ae. arabicum accessions (TUR and CYP) we identify substantial differences in glucosinolate profiles and quantities between lines, tissues and developmental stages...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/28599071/predator-odor-evokes-sex-independent-stress-responses-in-male-and-female-wistar-rats-and-reduces-phosphorylation-of-cyclic-adenosine-monophosphate-response-element-binding-protein-creb-in-the-male-but-not-the-female-hippocampus
#12
Damek Homiack, Emma O'Cinneide, Sema Hajmurad, Brett Barrileaux, Mary Stanley, Michael R Kreutz, Laura Schrader
Post-traumatic stress disorder (PTSD) is characterized by memory disturbances following trauma. Acute predator threat has emerged as an ethological model of PTSD, yet the effects of predator odor on signaling cascades associated with long-term memory remain poorly understood. In this study, we exposed male and female Wistar rats to the synthetic predator odor 2,5-dihydro-2,4,5-trimethylthiazoline (TMT) to assess behavioral and physiological responses as well as rapid modulation of signal transduction cascades associated with learning and memory in the male and female hippocampus...
June 9, 2017: Hippocampus
https://www.readbyqxmd.com/read/28598423/diversity-spurs-diversification-in-ecological-communities
#13
Vincent Calcagno, Philippe Jarne, Michel Loreau, Nicolas Mouquet, Patrice David
Diversity is a fundamental, yet threatened, property of ecological systems. The idea that diversity can itself favour diversification, in an autocatalytic process, is very appealing but remains controversial. Here, we study a generalized model of ecological communities and investigate how the level of initial diversity influences the possibility of evolutionary diversification. We show that even simple models of intra- and inter-specific ecological interactions can predict a positive effect of diversity on diversification: adaptive radiations may require a threshold number of species before kicking-off...
June 9, 2017: Nature Communications
https://www.readbyqxmd.com/read/28592527/zika-virus-hijacks-stress-granule-proteins-and-modulates-the-host-stress-response
#14
Shangmei Hou, Anil Kumar, Zaikun Xu, Adriana M Airo, Iryna Stryapunina, Cheung Pang Wong, William Branton, Egor Tchesnokov, Matthias Götte, Christopher Power, Tom C Hobman
Zika virus (ZIKV), a member of the Flaviviridae family, has recently emerged as an important human pathogen with increasing economic and health impact worldwide. Because of its teratogenic nature and association with the serious neurological condition Guillain-Barré syndrome, a tremendous amount of effort has focused on understanding ZIKV pathogenesis. To gain further insights into ZIKV interaction with host cells, we investigated how this pathogen affects stress response pathways. While ZIKV infection induces stress signaling that leads to phosphorylation of eIF2α and cellular translational arrest, stress granule (SG) formation was inhibited...
June 7, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28591556/regulation-of-usp7-a-high-incidence-of-e3-complexes
#15
REVIEW
Robbert Q Kim, Titia K Sixma
Ubiquitin conjugation is a critical signalling process in eukaryotic cells. The precise regulation of deubiquitination is an important component of this signalling cascade. Here we discuss how USP7 (or HAUSP), one of the most abundant deubiquitinating enzymes (DUBs) is regulated by complex formation with regulatory proteins and targets. Full activity of USP7 requires that its C-terminal ubiquitin-like domains fold back onto the catalytic domain, to allow remodelling of the active site to a catalytically competent state by the very C-terminal peptide...
June 4, 2017: Journal of Molecular Biology
https://www.readbyqxmd.com/read/28587227/photoreceptor-phyb-involved-in-arabidopsis-temperature-perception-and-heat-tolerance-formation
#16
Junyi Song, Qijun Liu, Biru Hu, Wenjian Wu
The influence of temperature on plants is essential. However, our knowledge on the intricate regulation process underlying heat stress (HS) response in plants is limited. Recently, information about thermal sensors in vivo has begun to emerge. In this study, another primary environmental stimulus, light, was verified once again to work with temperature synergistically on plants, through the modulation of numerous biological processes. With the application of transcriptomic analysis, a substantial number of heat-responsive genes were detected involved in both light- and phytohormone-mediated pathways in Arabidopsis...
June 5, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28585936/letting-go-bacterial-genome-reduction-solves-the-dilemma-of-adapting-to-predation-mortality-in-a-substrate-restricted-environment
#17
Michael Baumgartner, Stefan Roffler, Thomas Wicker, Jakob Pernthaler
Resource limitation and predation mortality are major determinants of microbial population dynamics, and optimization for either aspect is considered to imply a trade-off with respect to the other. Adaptation to these selective factors may, moreover, lead to disadvantages at rich growth conditions. We present an example of a concomitant evolutionary optimization to both, substrate limitation and predation in an aggregate-forming freshwater bacterial isolate, and we elucidate an underlying genomic mechanism...
June 6, 2017: ISME Journal
https://www.readbyqxmd.com/read/28585808/evidence-for-improved-encapsulated-pathway-behavior-in-a-bacterial-microcompartment-through-shell-protein-engineering
#18
Marilyn Faye Slininger Lee, Christopher M Jakobson, Danielle Tullman-Ercek
Bacterial microcompartments are a class of proteinaceous organelles comprising a characteristic protein shell enclosing a set of enzymes. Compartmentalization can prevent escape of volatile or toxic intermediates, prevent off-pathway reactions, and create private cofactor pools. Encapsulation in synthetic microcompartment organelles will enhance the function of heterologous pathways, but to do so, it is critical to understand how to control diffusion in and out of the microcompartment organelle. To this end, we explored how small differences in the shell protein structure result in changes in the diffusion of metabolites through the shell...
June 6, 2017: ACS Synthetic Biology
https://www.readbyqxmd.com/read/28585623/photocatalyzed-cascade-oxidative-annulation-of-propargylamines-and-phosphine-oxides
#19
Zheng-Guang Wu, Xiao Liang, Jie Zhou, Lei Yu, Yi Wang, You-Xuan Zheng, Yu-Feng Li, Jing-Lin Zuo, Yi Pan
On account of the broad utilities of organophosphorus compounds, the development of highly efficient and concise phosphination methods is significantly important and urgent. Herein, we disclose a novel method for the synthesis of phosphorylated heterocycles: versatile intermediate propargylamines serving as a new type of radical acceptors incorporated in P-radicals via a photocatalytic strategy. This reaction proceeds through a cascade phosphinoylation/cyclization/oxidation/aromatization pathway using readily available starting materials under mild conditions of light with excellent atom economy, catalyzed by AgOAc or fac-Ir(ppy)3...
June 16, 2017: Chemical Communications: Chem Comm
https://www.readbyqxmd.com/read/28582430/a-multi-objective-decision-making-approach-to-the-journal-submission-problem
#20
Tony E Wong, Vivek Srikrishnan, David Hadka, Klaus Keller
When researchers complete a manuscript, they need to choose a journal to which they will submit the study. This decision requires to navigate trade-offs between multiple objectives. One objective is to share the new knowledge as widely as possible. Citation counts can serve as a proxy to quantify this objective. A second objective is to minimize the time commitment put into sharing the research, which may be estimated by the total time from initial submission to final decision. A third objective is to minimize the number of rejections and resubmissions...
2017: PloS One
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