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Meredith A Skiba, Finn P Maloney, Qingyun Dan, Amy E Fraley, Courtney C Aldrich, Janet L Smith, W Clay Brown
The structural diversity and complexity of marine natural products have made them a rich and productive source of new bioactive molecules for drug development. The identification of these new compounds has led to extensive study of the protein constituents of the biosynthetic pathways from the producing microbes. Essential processes in the dissection of biosynthesis have been the elucidation of catalytic functions and the determination of 3D structures for enzymes of the polyketide synthases and nonribosomal peptide synthetases that carry out individual reactions...
2018: Methods in Enzymology
Zsolt Tidrenczel, Erika P Tardy, Edina Sarkadi, Judit Simon, Artúr Beke, János Demeter
Pallister-Killian syndrome (PKS) is a rare, sporadic genetic disorder that is caused by the mosaic presence of a supernumerary marker chromosome, isochromosome 12p. The syndrome is a polydysmorphic condition characterized by mental retardation, craniofacial dysmorphism, hypotonia, seizures, epilepsy and certain organic malformations (diaphragmatic hernia, congenital heart disease). Prenatal diagnosis is challenging due to the mosaic tissue-specific distribution of the chromosomal disorder and highly variable phenotype...
May 2018: Orvosi Hetilap
Kasuga Horai, Munekazu Naito, Tomiko Yakura, Yuka Furuya, Yusuke Ohmichi, Mika Ohmichi, Takayoshi Miyaki, Takashi Nakano
The pancake kidney (PK) is a rare type of renal anomaly in which both kidneys completely fuse without an isthmus. In the previous reports, PKs have double ureters and are located in the pelvic cavity. We encountered a rare case of PK with a single ureter, which is located in the left retroperitoneal space, in a 95-year-old female cadaver, which was detected during a dissection course. In our case, the major calyces joined to form a single renal pelvis, which continued as a single ureter. To the best of our knowledge, this is the first report on PK with a single ureter that is located not in the pelvic cavity but in the retroperitoneal space...
May 18, 2018: Anatomical Science International
Sarah Tomkovich, Christian Jobin
A recent study by Dejea et al. has demonstrated that two enterotoxigenic bacteria frequently associated with sporadic colorectal cancer, Bacteroides fragilis and pks+ Escherichia coli, are found together in biofilms on tissue from patients with familial adenomatous polyposis. In preclinical mouse models, these two bacteria and their corresponding toxins work synergistically to promote colon cancer.
May 18, 2018: British Journal of Cancer
Jun Yan, Guilin Li, Xingqi Guo, Yang Li, Xuecheng Cao
The protein kinase (PK, kinome) family is one of the largest families in plants and regulates almost all aspects of plant processes, including plant development and stress responses. Despite their important functions, comprehensive functional classification, evolutionary analysis and expression patterns of the cotton PK gene family has yet to be performed on PK genes. In this study, we identified the cotton kinomes in the Gossypium raimondii, Gossypium arboretum, Gossypium hirsutum and Gossypium barbadense genomes and classified them into 7 groups and 122-24 subfamilies using software HMMER v3...
2018: PloS One
Xiuyuan Li, Natalia Sevillano, Florencia La Greca, Lindsay Deis, Yu-Chen Liu, Marc C Deller, Irimpan I Mathews, Tsutomu Matsui, David E Cane, Charles S Craik, Chaitan Khosla
Catalytic modules of assembly-line polyketide synthases (PKSs) have previously been observed in two very different conformations-an "extended" architecture and an "arch-shaped" architecture-although the catalytic relevance of neither has been directly established. By the use of a fully human naïve antigen-binding fragment (Fab ) library, a high-affinity antibody was identified that bound to the extended conformation of a PKS module, as verified by X-ray crystallography and tandem size-exclusion chromatography-small-angle X-ray scattering (SEC-SAXS)...
May 18, 2018: Journal of the American Chemical Society
Chu Peng, He Wang, Yingying Jiang, Jinhua Yang, Hangxian Lai, Xiaomin Wei
Thus far, no studies have investigated the soil microbial diversity over an elevational gradient in Taibai Mountain, the central massif of the Qinling Mountain Range. Here, we used Illumina sequencing and quantitative PCR of the 16S rRNA gene to assess the diversity and abundance of bacterial communities along an elevational gradient in representative vegetation soils in Taibai Mountain. We identified the soil, climate, and vegetation factors driving the variations in soil bacterial community structure by Pearson correlation and redundancy analysis...
May 10, 2018: Microbial Ecology
Salmaan Kanji, Jason A Roberts, Jiao Xie, Abdulaziz Alobaid, Sheryl Zelenitsky, Swapnil Hiremath, Guijun Zhang, Irene Watpool, Rebecca Porteous, Rakesh Patel
BACKGROUND: Sustained low-efficiency dialysis (SLED), is increasingly being used in intensive care units (ICUs) but studies informing drug dosing for such patients is lacking. OBJECTIVE: To describe the population pharmacokinetics (PKs) of piperacillin/tazobactam in critically ill adults receiving SLED and to provide dosing recommendations. METHODS: This prospective population PK study was conducted in adult ICU patients prescribed piperacillin/tazobactam while receiving SLED; 321 blood samples were obtained from 34 participants during and between approximately 50 SLED treatments for quantification of piperacillin and tazobactam concentrations in plasma...
May 1, 2018: Annals of Pharmacotherapy
Zothanpuia, Ajit Kumar Passari, Vincent Vineeth Leo, Preeti Chandra, Brijesh Kumar, Chandra Nayak, Abeer Hashem, Elsayed Fathi Abd Allah, Abdulaziz A Alqarawi, Bhim Pratap Singh
BACKGROUND: Actinobacteria from freshwater habitats have been explored less than from other habitats in the search for compounds of pharmaceutical value. This study highlighted the abundance of actinobacteria from freshwater sediments of two rivers and one lake, and the isolates were studied for their ability to produce antimicrobial bioactive compounds. RESULTS: 16S rRNA gene sequencing led to the identification of 84 actinobacterial isolates separated into a common genus (Streptomyces) and eight rare genera (Nocardiopsis, Saccharopolyspora, Rhodococcus, Prauserella, Amycolatopsis, Promicromonospora, Kocuria and Micrococcus)...
May 5, 2018: Microbial Cell Factories
A Paganelli, S Bassoli, L Roncati, L Bigi, S Ciardo, G Pellacani
First described in 1965 by Mali et al., pseudo-Kaposi sarcoma (PKS), also known as acroangiodermatitis, is a rare disease inscribed in the setting of cutaneous reactive angiomatoses (CRAs). CRA are all characterized by occlusion and/or inflammation of cutaneous vessels, followed by histiocyte recruitment and endotheliocyte and pericyte hyperplasia. As the name suggests, PKS nearly resembles Kaposi sarcoma, but is benign in its nature. PKS typically presents with violaceous papules and plaques, usually located on the inferior limbs...
May 5, 2018: Journal of the European Academy of Dermatology and Venereology: JEADV
Natalie Heimerl, Elisabeth Hommel, Martin Westermann, Doreen Meichsner, Martin Lohr, Christian Hertweck, Arthur R Grossman, Maria Mittag, Severin Sasso
Polyketide synthases (PKSs) occur in many bacteria, fungi and plants. They are highly versatile enzymes involved in the biosynthesis of a large variety of compounds including antimicrobial agents, polymers associated with bacterial cell walls and plant pigments. While harmful algae are known to produce polyketide toxins, sequences of the genomes of non-toxic algae, including those of many green-algal species, have surprisingly revealed the presence of genes encoding type I PKSs. The genome of the model alga Chlamydomonas reinhardtii (Chlorophyta) contains a single type I PKS gene, designated PKS1 (Cre10...
May 4, 2018: Plant Journal: for Cell and Molecular Biology
Tao Zhu, Thibault Scalvenzi, Nathalie Sassoon, Xuefeng Lu, Muriel Gugger
Cyanobacteria can synthesize alkanes and alkenes, which are considered to be infrastructure-compatible biofuels. In terms of physiological function, cyanobacterial hydrocarbons are thought to be essential for membrane flexibility for cell division, size, and growth. The genetic basis for the biosynthesis of terminal olefins (1-alkenes) is a modular type I polyketide synthase (PKS) termed olefin synthase (Ols). The modular architectures of Ols and structural characteristics of alkenes have been investigated only in a few species of the small percentage (approximately 10%) of cyanobacteria that harbor putative Ols pathways...
May 4, 2018: Applied and Environmental Microbiology
Ruijie Gao, Huaxiang Deng, Zhengbing Guan, Xiangru Liao, Yujie Cai
Shiraia bambusicola is an important and valuable macrofungus and hypocrellins are its main secondary metabolites which have been widely applied in many medical fields. However, during SSF process of this filamentous fungus, use ratio of corn substrate and dissolved oxygen supply are two main limiting factors, which influence production cost, yield and product quality. To solve these problems, overexpressions of amy365-1 and vgb in S. bambusicola were investigated and three overexpression transformants were constructed...
May 2, 2018: AMB Express
Aurélie Lagarde, Patricia Jargeat, Mélanie Roy, Marion Girardot, Christine Imbert, Marion Millot, Lengo Mambu
Fungal communities associated to three epiphytic lichens active against Candida, were investigated using culture-based methods We hypothetized that associated fungi would contribute to lichens activities. The ability of specific fungi to grow inside or outside lichens was investigated. To detect biogenesis pathways involved in the production of secondary metabolites, genes coding for nonribosomal peptide synthetase (NRPS) and polyketide synthase I (PKS I) were screened by PCR from fungal DNA extracts. Both endo and epilichenic communities were isolated from two fructicose (Evernia prunastri and Ramalina fastigiata) and one foliose (Pleurosticta acetabulum) lichens...
June 2018: Microbiological Research
Yanglei Yi, Zhenhua Zhang, Fan Zhao, Huan Liu, Lijun Yu, Jiwei Zha, Gaoxue Wang
This study evaluated the probiotic potential of B. velezensis JW through experimental and genomic analysis approaches. Strain JW showed antimicrobial activity against a broad range of fish pathogenic bacteria including Aeromonas hydrophila, Aeromonas salmonicida, Lactococcus garvieae, Streptococcus agalactiae, and Vibrio Parahemolyticus. Fish (Carassius auratus) were fed with the diets containing 0 (control), 107 , and 109  cfu/g of B. velezensis JW for 4 weeks. Various immune parameters were examined at 1, 2, 3, and 4 weeks of post-feeding...
April 24, 2018: Fish & Shellfish Immunology
Meredith A Skiba, Andrew P Sikkema, Nathan A Moss, Andrew N Lowell, Min Su, Rebecca M Sturgis, Lena Gerwick, William H Gerwick, David H Sherman, Janet L Smith
The unusual feature of a t-butyl group is found in several marine-derived natural products including apratoxin A, a Sec61 inhibitor produced by the cyanobacterium Moorea bouillonii PNG 5-198. Here we determine that the apratoxin A t-butyl group is formed as pivaloyl acyl carrier protein (ACP) by AprA, the polyketide synthase (PKS) loading module of the apratoxin A biosynthetic pathway. AprA contains an inactive "pseudo" GCN5-related N-acetyltransferase domain (ΨGNAT) flanked by two methyltransferase domains (MT1 and MT2) that differ distinctly in sequence...
April 27, 2018: ACS Chemical Biology
Amreesh Parvez, Samir Giri, Gorkha Raj Giri, Monika Kumari, Renu Bisht, Priti Saxena
Mycobacterial pathogenesis is hallmarked by lipidic polyketides that decorate the cell envelope and mediate infection. However, factors mediating persistence remain largely unknown. Dynamic cell wall remodeling could facilitate the different pathogenic phases. Recent studies have implicated type III polyketide synthases (PKSs) in cell wall alterations in several bacteria. Comparative genome analysis revealed several type III pks gene clusters in mycobacteria. In this study, we report the functional characterization of two novel type III PKSs, MMAR_2470 and MMAR_2474, in Mycobacterium marinum...
April 25, 2018: Scientific Reports
Will Skyrud, Joyce Liu, Divya Thankachan, Maria Cabrera, Ryan F Seipke, Wenjun Zhang
Antimycins are a family of natural products possessing outstanding biological activities and unique structures, which have intrigued chemists for over a half century. Of particular interest are the ring-expanded antimycins that show promising anti-cancer potential and whose biosynthesis remains uncharacterized. Specifically, neoantimycin and its analogs have been shown to be effective regulators of the oncogenic proteins GRP78/BiP and K-Ras. The neoantimycin structural skeleton is built on a 15-membered tetralactone ring containing one methyl, one hydroxy, one benzyl and three alkylmoieties, as well as an amide linkage to a conserved 3-formamidosalicylic acid moiety...
April 25, 2018: ACS Chemical Biology
Hyungsub Kim, Hee Youn Choi, Yo-Han Kim, Kyun-Seop Bae, Jina Jung, Hankil Son, Hyeong-Seok Lim
Purpose: Rosuvastatin is a synthetic 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor that effectively reduces low-density lipoprotein cholesterol levels. However, statin monotherapy does not always achieve acceptable low-density lipoprotein cholesterol levels in patients with severe hypercholesterolemia. Ezetimibe, a selective cholesterol-absorption inhibitor, is approved for use as a monotherapy or combination therapy with 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors for patients with hypercholesterolemia...
2018: Drug Design, Development and Therapy
Wenling Zhang, Zhichao Guo, Weiwei Wang, Yonghui Sun, Chenxi Zhang, Xiaofei Wang, Liwen Zhang, Chengbin Wang
OBJECTIVE: To explore the clinical and genetic characteristics of a case with Pallister-Killian syndrome (PKS). METHODS: Chromosomal karyotype of umbilical cord blood sample derived from a 36-year-old pregnant woman was analyzed by G-banding analysis. After birth, the child was further analyzed with single nucleotide polymorphism microarray (SNP array) and fluorescence in situ hybridization (FISH) using 12pter/12qter probes. RESULTS: G-banding analysis showed that the fetus has a karyotype of 46,XY [77]/47,XY,+mar [23]...
April 10, 2018: Zhonghua Yi Xue Yi Chuan Xue za Zhi, Zhonghua Yixue Yichuanxue Zazhi, Chinese Journal of Medical Genetics
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