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N-Ethyl-N-Nitrosourea (ENU) Mutagenesis Reveals an Intronic Residue critical for caenorhabditis elegans 3 Splice Site Function in Vivo

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G3-GENES GENOMES GENETIcS 2016年第6期6卷 1751-1756页

作者： Itani, Omar A. Flibotte, Stephane Dumas, Kathleen J. Guo, chunfang Blumenthal, Thomas Hu, Patrick J. Univ Michigan Inst Gerontol Sch Med 3027 BSRB109 Zina Pitcher Pl Ann Arbor MI 48109 USA Univ Michigan Dept Internal Med Sch Med 3027 BSRB109 Zina Pitcher Pl Ann Arbor MI 48109 USA Univ Michigan Dept Cell & Dev Biol Sch Med 3027 BSRB109 Zina Pitcher Pl Ann Arbor MI 48109 USA Univ British Columbia Dept Zool Vancouver BC V6T 123 Canada Univ Colorado Dept Mol Cellular & Dev Biol Boulder CO 80309 USA Univ Washington Sch Med Dept Anesthesiol & Pain Med Seattle WA 98105 USA Buck Inst Res Aging Novato CA 94945 USA

Metazoan introns contain a polypyrimidine tract immediately upstream of the AG dinucleotide that defines the 3 splice site. In the nematode caenorhabditis elegans, 3 splice sites are characterized by a highly conserved UUUUcAG/R octamer motif. While the conservation of pyrimidines in this motif is strongly suggestive of their importance in pre-mRNA splicing, in vivo evidence in support of this is lacking. In an N-ethyl-N-nitrosourea (ENU) mutagenesis screen in caenorhabditis elegans, we have isolated a strain containing a point mutation in the octamer motif of a 3 splice site in the daf-12 gene. This mutation, a single base T-to-G transversion at the -5 position relative to the splice site, causes a strong daf-12 loss-of-function phenotype by abrogating splicing. The resulting transcript is predicted to encode a truncated DAF-12 protein generated by translation into the retained intron, which contains an in-frame stop codon. Other than the perfectly conserved AG dinucleotide at the site of splicing, G at the -5 position of the octamer motif is the most uncommon base in c. elegans 3 splice sites, occurring at closely paired sites where the better match to the splicing consensus is a few bases downstream. Our results highlight both the biological importance of the highly conserved -5 uridine residue in the c. elegans 3 splice site octamer motif as well as the utility of using ENU as a mutagen to study the function of polypyrimidine tracts and other AU- or AT-rich motifs in vivo.

关键词： c elegans splicing 3 splice site polypyrimidine tract daf-12 ENU

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Targeting inflammation in metabolic syndrome

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TRANSLATIONAL RESEARcH 2016年第1期167卷 257-280页

作者： Welty, Francine K. Alfaddagh, Abdulhamied Elajami, Tarec K. Harvard Univ Beth Israel Deaconess Med Ctr Sch Med Div Cardiol Boston MA 02215 USA

The metabolic syndrome (MetS) is comprised of a cluster of closely related risk factors, including visceral adiposity, insulin resistance, hypertension, high triglyceride, and low high-density lipoprotein cholesterol;all of which increase the risk for the development of type 2 diabetes and cardiovascular disease. A chronic state of inflammation appears to be a central mechanism underlying the pathophysiology of insulin resistance and MetS. In this review, we summarize recent research which has provided insight into the mechanisms by which inflammation underlies the pathophysiology of the individual components of MetS including visceral adiposity, hyperglycemia and insulin resistance, dyslipidemia, and hypertension. On the basis of these mechanisms, we summarize therapeutic modalities to target inflammation in the MetS and its individual components. current therapeutic modalities can modulate the individual components of MetS and have a direct anti-inflammatory effect. Lifestyle modifications including exercise, weight loss, and diets high in fruits, vegetables, fiber, whole grains, and low-fat dairy and low in saturated fat and glucose are recommended as a first line therapy. The Mediterranean and dietary approaches to stop hypertension diets are especially beneficial and have been shown to prevent development of MetS. Moreover, the Mediterranean diet has been associated with reductions in total and cardiovascular mortality. Omega-3 fatty acids and peroxisome proliferator-activated receptor alpha agonists lower high levels of triglyceride;their role in targeting inflammation is reviewed. Angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and aldosterone blockers comprise pharmacologic therapies for hypertension but also target other aspects of MetS including inflammation. Statin drugs target many of the underlying inflammatory pathways involved in MetS.

关键词： AA arachidonic acid ABcA1 adenosine triphosphate-binding cassette transporter A1 AcE-I angiotensin-converting enzyme inhibitor AcSL1 acyl-coA synthase 1 ADMA asymmetric dimethylarginine Akt protein kinase B Aldo aldosterone AMPK adenosine monophosphate-activated protein kinase ANGPTL angiopoietin-like protein Ang angiotensin AngII angiotensin II AP-1 activator protein 1 Apo apolipoprotein ARB angiotensin receptor blocker Aspirin-cOX-2 aspirin-acetylated cyclooxygenase-2 AT-LX aspirin-triggered lipoxins AT-PD1 aspirin-triggered protectins AT-RvD aspirin-triggered resolvins c cholesterol cAD coronary artery disease cD cluster of differentiation cE cholesterol ester cETP cE transfer protein coQ10 coenzyme Q10 cOX cyclooxygenase cOX-2 cyclooxygenase-2 cRP c-reactive protein c-Src tyrosine-protein kinase c-Src Kinase cVD cardiovascular disease DAG diacylglycerides DHA docosahexaenoic acid EF ejection fraction eNOS endothelial nitric oxide synthase EPA eicosapentaenoic acid ET endothelin FetA Fetuin A FFA free fatty acids FoxO1 forkhead box protein O1 Glu glucose GLUT-4 glucose transporter type 4 GPR G-protein–coupled receptor GRK2 G-protein–coupled receptor kinase 2 HDL high-density lipoprotein HL hepatic lipase HR hazard ratio IcAM-1 intercellular adhesion molecule-1 IDL intermediate-density lipoprotein IKK inhibitor of nuclear factor kappa-B kinase IL interleukin ILR interleukin receptor iNOS inducible nitric oxide synthase LT leukotriene IRS insulin receptor substrate IκB inhibitor of nuclear factor kappa-B JNK c-Jun N-terminal kinase LOX lipoxygenase LPL lipoprotein lipase LX lipoxin MAPK Mitogen-activated protein kinases McP-1 monocyte chemoattractant protein-1 MetS metabolic syndrome MI myocardial infarction MMP matrix metalloproteinase MTP microsomal triglyceride transfer protein NF-κB nuclear factor kappa-B NLR nod-like receptor NO nitric oxide Omega-3 FAs omega-3 fatty acids oxLDL oxidized low-density lipoprotein PAI-1 plasminogen activator inhibitor-1 PD1 protectins PG prostaglandins PI3K phosphatidylinosito

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The Stress Granule RNA-Binding Protein TIAR-1 Protects Female Germ cells from Heat Shock in caenorhabditis elegans

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G3-GENES GENOMES GENETIcS 2016年第4期6卷 1031-1047页

作者： Huelgas-Morales, Gabriela Giovanni Silva-Garcia, carlos Salinas, Laura S. Greenstein, David Navarro, Rosa E. Univ Nacl Autonoma Mexico Inst Fisiol Celular Dept Biol Celular & Desarrollo Circuito Exterior S-NCiudad Univ Mexico City 04510 DF Mexico Univ Minnesota Dept Genet Cell Biol & Dev 4-208 MCB420 Washington Ave SE Minneapolis MN 55455 USA

In response to stressful conditions, eukaryotic cells launch an arsenal of regulatory programs to protect the proteome. One major protective response involves the arrest of protein translation and the formation of stress granules, cytoplasmic ribonucleoprotein complexes containing the conserved RNA-binding proteins TIA-1 and TIAR. The stress granule response is thought to preserve mRNA for translation when conditions improve. For cells of the germlinethe immortal cell lineage required for sexual reproductionprotection from stress is critically important for perpetuation of the species, yet how stress granule regulatory mechanisms are deployed in animal reproduction is incompletely understood. Here, we show that the stress granule protein TIAR-1 protects the caenorhabditis elegans germline from the adverse effects of heat shock. Animals containing strong loss-of-function mutations in tiar-1 exhibit significantly reduced fertility compared to the wild type following heat shock. Analysis of a heat-shock protein promoter indicates that tiar-1 mutants display an impaired heat-shock response. We observed that TIAR-1 was associated with granules in the gonad core and oocytes during several stressful conditions. Both gonad core and oocyte granules are dynamic structures that depend on translation;protein synthesis inhibitors altered their formation. Nonetheless, tiar-1 was required for the formation of gonad core granules only. Interestingly, the gonad core granules did not seem to be needed for the germ cells to develop viable embryos after heat shock. This suggests that TIAR-1 is able to protect the germline from heat stress independently of these structures.

关键词： stress granules TIA-1 TIAR germ cells stress c elegans

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计算机语言发展概述

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电子制作 2019年第4期27卷 56-57,67页

作者：李冠岑湖北省宜昌市第一中学湖北宜昌443000

计算机程序的发展为计算机的普及应用起到了极大的促进作用,计算机语言也随着计算机技术的不断发展在不断的改进。本文对计算机语言的发展情况及常用的编程语言进行简要介绍。

关键词：计算机语言 Python Java c

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Phytotoxicity comparison of organic contaminants and heavy metals using chlorella vulgaris

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DESALINATION AND WATER TREATMENT 2016年第44期57卷 20809-20816页

作者： Wu, Maoni N. Wang, Xiaochang c. Ma, Xiaoyan Y. Xian Univ Architecture & Technol Key Lab Northwest Water Resources Environm & Ecol Minist Educ Xian 710055 Peoples R China

The green alga chlorella vulgaris (c. vulgaris) is proposed as a test species for the phytotoxicity assessment of organic contaminants and heavy metals. The relationship between concentration and inhibition was established from the phytotoxic effects on c. vulgaris over a long-term exposure of 72h. The concentration for 50% of maximal effect (Ec50,metal) for cr, cd, Hg, cu, Ni, Zn, and Pb was 0.11, 0.13, 0.22, 0.24, 0.28, 1.13, and 5.69mg/L, respectively. On the other hand, the Ec50,TOc total organic carbon (TOc) for trichloroisocyanuric acid (TccA), 1-naphthylamine, sodium dodecylbenzene sulfonate, ciprofloxacin, Acetaminophen, phenol was 0.02, 1.50, 5.99, 17.23, 55.79, and 236mg/L, respectively. For raw sewage and secondary effluent from a domestic wastewater treatment plant (WWTP), Ec50,TOc of 53.88 and 70.94mg/L was obtained by concentrating organic matter through reverse osmosis. This result suggests that WWTPs reduce not only the organic compounds concentration, but also the phytotoxicity of wastewaters. Through a combined analysis of the concentrations of organic compounds and heavy metals, and the phytotoxicity of two typical industrial wastewaters, it was ascertained that the phytotoxicities of coking wastewater and brewery wastewaters were mainly caused by the organic contaminants. Nonetheless, the phytotoxicity of coking wastewater (toxicity index of Ec50,%=0.37%) was significantly higher than that of brewery wastewater (Ec50,%=32%). This difference in phytotoxicity may be because the coking wastewater contains more toxic organic contaminants (Ec50,TOc=32.95mg/L) than the brewery wastewater (Ec50,TOc=258.4mg/L).

关键词： Phytotoxicity c vulgaris Heavy metal Organic contaminants Wastewater

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A novel bipartite UNc-101/AP-1 1 binding signal mediates KVS-4/Kv2.1 somatodendritic distribution in caenorhabditis elegans

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FEBS LETTERS 2016年第1期590卷 76-92页

作者： Zhou, Xin Zeng, Jia Ouyang, chenxi Luo, Qianyun Yu, Miao Yang, Zhenrong Wang, Hui Shen, Kang Shi, Anbing Huazhong Univ Sci & Technol Tongji Med Coll Sch Basic Med Dept Med Genet 13 Hangkong Rd Wuhan 430030 Hubei Peoples R China Huazhong Univ Sci & Technol Tongji Med Coll Collaborat Innovat Ctr Brain Sci 13 Hangkong Rd Wuhan 430030 Hubei Peoples R China Huazhong Univ Sci & Technol Union Hosp Tongji Med Coll Dept Vasc Surg 13 Hangkong Rd Wuhan 430030 Hubei Peoples R China Stanford Univ Howard Hughes Med Inst Dept Biol Palo Alto CA 94304 USA Huazhong Univ Sci & Technol Inst Brain Res 13 Hangkong Rd Wuhan 430030 Hubei Peoples R China Huazhong Univ Sci & Technol Tongji Med Coll Natl Educ Minist Key Lab Neurol Dis 13 Hangkong Rd Wuhan 430030 Hubei Peoples R China

Potassium channels such as Kv2.1 are targeted to specific subcellular compartments to fulfill various functions. However, the mechanisms for their localization are poorly understood. Here, we show that KVS-4/Kv2.1 somatodendritic localization in caenorhabditis elegansDA9 neuron requires UNc-101(AP-1 subunit). We define a bipartite sorting signal within KVS-4 consisting of a c-terminal EQMIL and N-terminal WNIIE motifs. The bipartite signal is sufficient to target nonpolarized transmembrane protein MIG-13 into DA9 somatodendritic compartments. Furthermore, we found that AP-1 interacts with the bipartite signal through UNc-101/AP-1 N-terminal predicted Longin-like domain. Our results provide new insight into the mechanisms of Kv2.1 post-Golgi sorting and targeting.

关键词： AP-1 c elegans KVS-4 Kv2 1 post-Golgi sorting

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The Black Bug Myth: Selective photodestruction of pigmented pathogens

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LASERS IN SURGERY AND MEDIcINE 2016年第7期48卷 706-714页

作者： Harris, David M. Jacques, Steven L. Darveau, Richard Biomed Consultants Inc 436 Green Oaks Dr Paradise CA 95969 USA Univ Washington Dept Otolaryngol Seattle WA 98195 USA Oregon Hlth & Sci Univ Dept Biomed Engn Portland OR 97239 USA Oregon Hlth & Sci Univ Dept Dermatol Portland OR 97239 USA Univ Washington Dept Periodont Seattle WA 98195 USA

Background and ObjectiveIt is commonly believed that pigmented pathogens are selectively targeted by dental lasers. To test this notion optical diffuse reflection spectroscopy (DRS) was used to obtain absorption spectra for the periodontal pathogens, Porphyromonas gingivalis (Pg) and Prevotella intermedia (Pi). Materials and MethodsSpectra from 400 to 1,100nm wavelengths of Pg colonies cultured with different concentrations of hemin were obtained to test the hypothesis that visual pigmentation predicts absorption of near-infrared (IR) dental laser energy. Ablation threshold at 1,064nm [1] was measured for the pathogenic fungus, candida albicans (ca). ResultsThe hypothesis was demonstrated to be true at 810nm, it was false at 1,064nm. Diode laser (810nm) efficacy and depth of kill is dependent on hemin availability from 400 to about 900nm. Pg and Pi absorption at 1,064nm (mu(a)=7.72.6cm(-1)) is independent of hemin availability but is determined by another unknown chromophore. ca is non-pigmented but very sensitive to 1,064nm irradiation. conclusionsThe amount of visual pigmentation does not necessarily predict sensitivity to dental laser irradiation. Spectra in visible and near-IR wavelengths demonstrate a large difference in absorption between soft tissue and Pg or Pi. This difference represents a host/pathogen differential sensitivity to laser irradiation, the basis for selective photoantisepsis. Lasers Surg. Med. 48:706-714, 2016. (c) 2016 Wiley Periodicals, Inc.

关键词： dental laser pulsed Nd:YAG 810nm diode tissue spectroscopy bacterial reduction periodontal pathogens P gingivalis (Pg) P intermedia (Pi) c albicans (ca)

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creating a Transducer Electronic Datasheet using I2c Serial EEPROM Memory and PIc32-Based Microcontroller Development Board 7

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7th International conference on Advanced Topics in Optoelectronics, Microelectronics, and Nanotechnologies (ATOM-N)

作者： croitoru, Bogdan Tulbure, Adrian Abrudean, Mihail Secara, Mihai 1 Decembrie 1918 Univ Alba Iulia Dept Precise & Engn Sci Alba Iulia Romania Tech Univ Cluj Napoca Dept Automat Cluj Napoca Romania

ISBN: (纸本)9781628413250

The present paper describes a software method for creating / managing one type of Transducer Electronic Datasheet (TEDS) according to IEEE 1451.4 standard in order to develop a prototype of smart multi-sensor platform (with up to ten different analog sensors simultaneously connected) with Plug & Play capabilities over ETHERNET and Wi-Fi. In the experiments were used: one analog temperature sensor, one analog light sensor, one PIc32-based microcontroller development board with analog and digital I/O ports and other computing resources, one 24Lc256 I2c (Inter Integrated circuit standard) serial Electrically Erasable Programmable Read Only Memory (EEPROM) memory with 32KB available space and 3 bytes internal buffer for page writes (1 byte for data and 2 bytes for address). It was developed a prototype algorithm for writing and reading TEDS information to / from I2c EEPROM memories using the standard c language (up to ten different TEDS blocks coexisting in the same EEPROM device at once). The algorithm is able to write and read one type of TEDS: transducer information with standard TEDS content. A second software application, written in VB. NET platform, was developed in order to access the EEPROM sensor information from a computer through a serial interface (USB).

关键词： IEEE 1451 smart sensors TEDS EEPROM microcontroller PIc embedded c Plug&Play

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Untangling the contributions of Sex-Specific Gene Regulation and X-chromosome Dosage to Sex-Biased Gene Expression in caenorhabditis elegans

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GENETIcS 2016年第1期204卷 355-+页

作者： Kramer, Maxwell Rao, Prashant Ercan, Sevinc NYU Dept Biol Ctr Genom & Syst Biol New York NY 10003 USA

Dosage compensation mechanisms equalize the level of X chromosome expression between sexes. Yet the X chromosome is often enriched for genes exhibiting sex-biased, i.e., imbalanced expression. The relationship between X chromosome dosage compensation and sex-biased gene expression remains largely unexplored. Most studies determine sex-biased gene expression without distinguishing between contributions from X chromosome copy number (dose) and the animal's sex. Here, we uncoupled X chromosome dose from sex-specific gene regulation in caenorhabditis elegans to determine the effect of each on X expression. In early embryogenesis, when dosage compensation is not yet fully active, X chromosome dose drives the hermaphrodite-biased expression of many X-linked genes, including several genes that were shown to be responsible for hermaphrodite fate. A similar effect is seen in the c. elegans germline, where X chromosome dose contributes to higher hermaphrodite X expression, suggesting that lack of dosage compensation in the germline may have a role in supporting higher expression of X chromosomal genes with female-biased functions in the gonad. In the soma, dosage compensation effectively balances X expression between the sexes. As a result, somatic sex-biased expression is almost entirely due to sex-specific gene regulation. These results suggest that lack of dosage compensation in different tissues and developmental stages allow X chromosome copy number to contribute to sex-biased gene expression and function.

关键词： dosage compensation c elegans RNA-seq sex sex-biased gene expression chromatin X chromosome transcription gene regulation germline XO genetics of sex

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Outcomes of clostridium difficile infection in pediatric solid organ transplant recipients

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TRANSPLANT INFEcTIOUS DISEASE 2016年第1期18卷 31-36页

作者： Pant, c. Deshpande, A. Desai, M. Jani, B. S. Sferra, T. J. Gilroy, R. Olyaee, M. Univ Kansas Med Ctr Dept Internal Med Div Gastroenterol Hepatol & Motil Kansas City KS 66103 USA Cleveland Clin Med Inst Ctr Value Based Care Cleveland OH 44106 USA Cleveland Clin Inst Med Dept Infect Dis Cleveland OH 44106 USA Rainbow Babies & Childrens Hosp Dept Pediat Divis Pediat Gastroenterol Hepatol & Nutr 2101 Adelbert Rd Cleveland OH 44106 USA

BackgroundThe incidence of clostridium difficile infection (cDI) is increasing in the pediatric population. Pediatric recipients of solid organ transplantation (SOT) may be at a higher risk for cDI in part because of chemotherapy and prolonged hospitalization. MethodsWe utilized data from the Healthcare cost and Utilization Project Kids' Inpatient Database to study the incidence and outcomes related to cDI as a complicating factor in pediatric recipients of SOT. ResultsOur results demonstrate that hospitalized children with SOT have increased rates of infection, with the greatest risk for younger children with additional comorbidities and severe illness. The type of transplanted organ affects the risk for cDI, with the lowest incidence observed in renal transplant patients. conclusionThe occurrence of cDI in the pediatric SOT population contributes to a greater length of stay and higher hospital charges. However, cDI is not an independent predictor of increased in- hospital mortality in these patients.

关键词： c difficile infection children incidence transplantation

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