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https://www.readbyqxmd.com/read/29035385/class-2-crispr-cas-rna-guided-endonucleases-swiss-army-knives-of-genome-editing
#1
REVIEW
Stefano Stella, Pablo Alcón, Guillermo Montoya
CRISPR-Cas is a bacterial defense system against phage infection and nucleic acid invasion. Class 2 type II CRISPR-Cas9 has also been widely used for genome engineering. Here, we review novel insights into the CRISPR class 2 type V enzymes, specifically Cpf1 and C2c1, which display different DNA-recognition and cleavage characteristics than those of Cas9, the best-characterized member of class 2. Recent structures of these ribonucleoprotein complexes that capture several stages of the endonuclease reaction have provided molecular details of recognition, unzipping and cleavage of the target DNA, allowing their comparison with Cas9...
October 16, 2017: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/29034843/research-progress-in-reversal-of-tumor-multi-drug-resistance-via-natural-products
#2
Qi Guo, Hongyan Cao, Xianghui Qi, Huikai Li, Peizhi Ye, Zhiguo Wang, Danqiao Wang, Hua Zhou, Jingui Xue, Mingyu Sun
Multidrug resistance (MDR) occurs when a tumor develops resistance to multiple chemotherapeutic drugs, which may include antitumor drugs with different chemical structures and mechanisms. MDR limits the treatment effects of antitumor drugs, and is the main cause of chemotherapy failure. MDR is caused by numerous factors including changes in ABC transporters, target proteins, detoxification, DNA repair, drug metabolic enzymes, and signal pathways of apoptosis. Clinical research indicates that natural products have great potential to treat tumors and reverse MDR...
October 16, 2017: Anti-cancer Agents in Medicinal Chemistry
https://www.readbyqxmd.com/read/29034472/protective-effects-of-curcumin-against-aflatoxicosis-a-comprehensive-review
#3
REVIEW
Mohammad Mohajeri, Behzad Behnam, Arrigo F G Cicero, Amirhossein Sahebkar
Aflatoxicosis is a deleterious medical condition that results from aflatoxins (AFs) or ochratoxins (OTs). Contamination with these toxins exerts detrimental effects on the liver, kidneys, reproductive organs, and also on immunological and cardiovascular systems. Aflatoxicosis is closely associated with overproduction of reactive oxygen species (ROS) as key contributors to oxidative and nitrosative stress responses, and subsequent damages to lipids, proteins, RNA, and DNA. The main target organ for AF toxicity is the liver, where DNA adducts, degranulation of endoplasmic reticulum, increased hepatic lipid peroxide, GSH depletion, mitochondrial dysfunction, and reduction of enzymatic and non-enzymatic antioxidants are manifestations of aflatoxicosis...
October 16, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29034064/personalized-therapy-against-preeclampsia-by-replenishing-placental-protein-13-pp13-targeted-to-patients-with-impaired-pp13-molecule-or-function
#4
REVIEW
Hamutal Meiri, George Osol, Irene Cetin, Sveinbjörn Gizurarson, Berthold Huppertz
Hypertensive disorders affect about one third of all people aged 20 and above, and are treated with anti-hypertensive drugs. Preeclampsia (PE) is one form of such disorders that only develops during pregnancy. It affects ten million pregnant women globally and additionally causes fetal loss and major newborn disabilities. The syndrome's origin is multifactorial, and anti-hypertensive drugs are ineffective in treating it. Biomarkers are helpful for predict its development. Generic drugs, such as low dose aspirin, were proven effective in preventing preterm PE...
2017: Computational and Structural Biotechnology Journal
https://www.readbyqxmd.com/read/29033785/versatile-roles-of-the-chromatin-remodeler-chd7-during-brain-development-and-disease
#5
REVIEW
Weijun Feng, Chunxuan Shao, Hai-Kun Liu
CHD7 (Chromo-Helicase-DNA binding protein 7) protein is an ATP-dependent chromatin remodeler. Heterozygous mutation of the CHD7 gene causes a severe congenital disease known as CHARGE syndrome. Most CHARGE syndrome patients have brain structural anomalies, implicating an important role of CHD7 during brain development. In this review, we summarize studies dissecting developmental functions of CHD7 in the brain and discuss pathogenic mechanisms behind neurodevelopmental defects caused by mutation of CHD7. As we discussed, CHD7 protein exhibits a remarkably specific and dynamic expression pattern in the brain...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/29029743/advances-of-vibrational-circular-dichroism-vcd-in-bioanalytical-chemistry-a-review
#6
REVIEW
Dmitry Kurouski
Vibrational Circular Dichroism (VCD) is a unique and relatively new spectroscopic technique that is capable of determining an absolute configuration of chiral molecules. VCD can be also used to determine structure of large macromolecules. This review highlights the most recent advances of VCD in bioanalytical chemistry. It shows that VCD is capable of unraveling supramolecular organization of peptides, proteins, saccharides, glycerophospholipids, polypeptide microcrystals, as well as amyloid fibrils and DNA...
October 16, 2017: Analytica Chimica Acta
https://www.readbyqxmd.com/read/28992434/targeting-epigenetics-in-cancer
#7
Richard L Bennett, Jonathan D Licht
Alterations of genes regulating epigenetic processes are frequently found as cancer drivers and may cause widespread alterations of DNA methylation, histone modification patterns, or chromatin structure that disrupt normal patterns of gene expression. Because of the inherent reversibility of epigenetic changes, inhibitors targeting these processes are promising anticancer strategies. Small molecules targeting epigenetic regulators have been developed recently, and clinical trials of these agents are under way for hematologic malignancies and solid tumors...
October 6, 2017: Annual Review of Pharmacology and Toxicology
https://www.readbyqxmd.com/read/28992351/modification-of-meiotic-recombination-by-natural-variation-in-plants
#8
Emma J Lawrence, Catherine H Griffin, Ian R Henderson
Meiosis is a specialized cell division that produces haploid gametes required for sexual reproduction. During the first meiotic division, homologous chromosomes pair and undergo reciprocal crossing over, which recombines linked sequence variation. Meiotic recombination frequency varies extensively both within and between species. In this review, we will examine the molecular basis of meiotic recombination rate variation, with an emphasis on plant genomes. We first consider cis modification caused by polymorphisms at the site of recombination, or elsewhere on the same chromosome...
September 6, 2017: Journal of Experimental Botany
https://www.readbyqxmd.com/read/28992135/auxin-response-factors-output-control-in-auxin-biology
#9
Mark Roosjen, Sébastien Paque, Dolf Weijers
The phytohormone auxin is involved in almost all developmental processes in land plants. Most, if not all, of these processes are mediated by changes in gene expression. Auxin acts on gene expression through a short nuclear pathway that converges upon the activation of a family of DNA-binding transcription factors. These AUXIN RESPONSE FACTORS (ARFs) are thus the effector of auxin response and translate the chemical signal into the regulation of a defined set of genes. Given the limited number of dedicated components in auxin signaling, distinct properties among the ARF family probably contribute to the establishment of multiple unique auxin responses in plant development...
July 24, 2017: Journal of Experimental Botany
https://www.readbyqxmd.com/read/28991194/parp1-in-carcinomas-and-parp1-inhibitors-as-antineoplastic-drugs
#10
REVIEW
Luyao Wang, Chao Liang, Fangfei Li, Daogang Guan, Xiaoqiu Wu, Xuekun Fu, Aiping Lu, Ge Zhang
Poly (ADP-ribose) polymerase 1 (PARP1), the best-studied isoform of the nuclear enzyme PARP family, plays a pivotal role in cellular biological processes, such as DNA repair, gene transcription, and so on. PARP1 has been found to be overexpressed in various carcinomas. These all indicate the clinical potential of PARP1 as a therapeutic target of human malignancies. Additionally, multiple preclinical research studies and clinical trials demonstrate that inhibition of PARP1 can repress tumor growth and metastasis...
October 8, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28990860/in-a-genomic-era-placental-pathology-still-holds-the-key-in-the-nondysmorphic-stillbirth
#11
Jamie Campbell, Kristy Armstrong, Nithiya Palaniappan, Eddy Maher, Mary Glancy, Mary Porteous, Kathryn J Mckenzie, Margaret J Evans
Objective To explore the relative utility of genetic testing in contrast to placental pathology in explaining causation of death in the structurally normal stillborn population. Methods A retrospective review of a structurally normal stillborn infant cohort in South East Scotland between 2011 and 2015, defined by death at or after 24 weeks of gestation. We reviewed pathology reports and collected demographic data on cases. This information was collated with genetic test results (quantitative fluorescent polymerase chain reaction and microarray analysis) and placental pathology to create a database for analysis...
January 1, 2017: Pediatric and Developmental Pathology
https://www.readbyqxmd.com/read/28990402/reassessing-the-structure-and-function-relationship-of-the-o-sub-2-sub-sensing-transcription-factor-fnr
#12
Erin L Mettert, Patricia Kiley
SIGNIFICANCE: The <i>Escherichia coli </i>regulatory protein FNR mediates a global transcriptional response upon O<sub>2</sub>-deprivation. Spanning nearly 40 years of research investigations, our understanding of how FNR senses and responds to O<sub>2</sub> has considerably progressed despite a lack of structural information for most of that period. This knowledge has established the paradigm for how facultative anaerobic bacteria sense changes in O<sub>2</sub> tension...
October 7, 2017: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/28989087/catanionic-systems-in-nanotherapeutics-biophysical-aspects-and-novel-trends-in-drug-delivery-applications
#13
REVIEW
Vivek V Dhawan, Mangal S Nagarsenker
Mixtures of surfactants can result in formation of various structures like micelles, vesicles and inverted micelles. Catanionic vesicular systems are preferred on account of their ease of formation and thermodynamic stability. Furthermore, their charge and surfactant properties render them as useful vehicles for DNA delivery and cytotoxic compounds. They suffer from disadvantages of being leaky and yielding low encapsulation efficiencies which are averse to drug delivery purposes. Extensive efforts are being undertaken to overcome these barriers and render these vesicles amenable to spatial placement and temporal delivery of drugs...
October 5, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28980535/the-nail-as-an-investigative-tool-in-medicine-what-a-dermatologist-ought-to-know
#14
REVIEW
Chander Grover, Shikha Bansal
The nail is an important skin appendage, but not many dermatologists are aware of the importance it receives outside our specialty. This article focuses on the nail in non-dermatological contexts. The nail is a keratinized matrix capable of continuous growth with the ability to incorporate various compounds within its structure. Therefore it can be used to monitor long-term consumption of drugs. It is also an excellent source of germ-line DNA for genetic analyses. With an increased undrstanding of nail physiology, there is now a better understanding of its connection to various pathologies as well...
October 4, 2017: Indian Journal of Dermatology, Venereology and Leprology
https://www.readbyqxmd.com/read/28977762/lung-cancer-heterogeneity-and-new-strategies-for-drug-therapy
#15
Diane C Wang, William Wang, Bijun Zhu, Xiangdong Wang
Lung cancer heterogeneity plays an important role in the development of drug resistance. Comprehensive molecular characterizations of lung cancer can describe hereditary and somatic gene changes, mutation, and heterogeneity. We discuss heterogeneity specificity, characterization, and roles of PIK3CD, TP53, and KRAS, as well as target-driven therapies and strategies applied in clinical trials based on a proposed precise self-validation system. The system is a specifically selected strategy of treatment for patients with cancer gene mutations and heterogeneity based on gene sequencing, following validation of the strategies in the patient's own cancer cells or in patientderived xenografts using their own cancer cells isolated during surgery or biopsies...
October 4, 2017: Annual Review of Pharmacology and Toxicology
https://www.readbyqxmd.com/read/28974036/protoparvovirus-knocking-at-the-nuclear-door
#16
REVIEW
Elina Mäntylä, Michael Kann, Maija Vihinen-Ranta
Protoparvoviruses target the nucleus due to their dependence on the cellular reproduction machinery during the replication and expression of their single-stranded DNA genome. In recent years, our understanding of the multistep process of the capsid nuclear import has improved, and led to the discovery of unique viral nuclear entry strategies. Preceded by endosomal transport, endosomal escape and microtubule-mediated movement to the vicinity of the nuclear envelope, the protoparvoviruses interact with the nuclear pore complexes...
October 2, 2017: Viruses
https://www.readbyqxmd.com/read/28970971/advances-in-the-study-of-nodavirus
#17
Chean Yeah Yong, Swee Keong Yeap, Abdul Rahman Omar, Wen Siang Tan
Nodaviruses are small bipartite RNA viruses which belong to the family of Nodaviridae. They are categorized into alpha-nodavirus, which infects insects, and beta-nodavirus, which infects fishes. Another distinct group of nodavirus infects shrimps and prawns, which has been proposed to be categorized as gamma-nodavirus. Our current review focuses mainly on recent studies performed on nodaviruses. Nodavirus can be transmitted vertically and horizontally. Recent outbreaks have been reported in China, Indonesia, Singapore and India, affecting the aquaculture industry...
2017: PeerJ
https://www.readbyqxmd.com/read/28969091/cellular-senescence-senescence-associated-secretory-phenotype-and-chronic-kidney-disease
#18
REVIEW
Wen-Juan Wang, Guang-Yan Cai, Xiang-Mei Chen
Chronic kidney disease (CKD) is increasingly being accepted as a type of renal ageing. The kidney undergoes age-related alterations in both structure and function. To date, a comprehensive analysis of cellular senescence and senescence-associated secretory phenotype (SASP) in CKD is lacking. Hence, this review mainly discusses the relationship between the two phenomena to show the striking similarities between SASP and CKD-associated secretory phenotype (CASP). It has been reported that replicative senescence, stress-induced premature ageing, and epigenetic abnormalities participate in the occurrence and development of CKD...
September 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28968850/epigenetic-regulation-of-gene-expression-in-cancer-techniques-resources-and-analysis
#19
Luciane T Kagohara, Genevieve L Stein-O'Brien, Dylan Kelley, Emily Flam, Heather C Wick, Ludmila V Danilova, Hariharan Easwaran, Alexander V Favorov, Jiang Qian, Daria A Gaykalova, Elana J Fertig
Cancer is a complex disease, driven by aberrant activity in numerous signaling pathways in even individual malignant cells. Epigenetic changes are critical mediators of these functional changes that drive and maintain the malignant phenotype. Changes in DNA methylation, histone acetylation and methylation, noncoding RNAs, posttranslational modifications are all epigenetic drivers in cancer, independent of changes in the DNA sequence. These epigenetic alterations were once thought to be crucial only for the malignant phenotype maintenance...
August 11, 2017: Briefings in Functional Genomics
https://www.readbyqxmd.com/read/28967283/redox-sensing-iron-sulfur-cluster-regulators
#20
J C Crack, Nick E Le Brun
SIGNIFICANCE: Iron-sulfur cluster proteins carry out a wide range of functions, including as regulators of gene transcription/translation in response to environmental stimuli. In all known cases, the cluster acts as the sensory module, where the inherent reactivity/fragility of iron-sulfur clusters towards small/redox active molecules is exploited to effect conformational changes that modulate binding to DNA regulatory sequences. This promotes an often substantial re-programming of the cellular proteome that enables the organism or cell to adapt to, or counteract, its changing circumstances...
October 1, 2017: Antioxidants & Redox Signaling
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