Damage to mRNA metabolism Sample Clauses

Damage to mRNA metabolism. ‌ Defective splicing of mRNA for the glial glutamate transporter EAAT2 in ALS patients was one of the first pieces of evidence linking RNA processing defects to excitotoxicity and motor neuron degeneration (Xxx et al., 1998). Moreover, mRNA oxidation in motor neurons is a common finding in ALS patients and SOD1 transgenic mice (Xxxxx et al., 2008). More recently, the importance of RNA metabolism has been highlighted by the discovery that mutations in genes encoding Senataxin, an RNA helicase, Angiogenin, a ribonuclease and RNA/DNA interacting proteins TDP43 and FUS all cause familial forms of ALS (Xxxx et al., 2004; Xxxxxxxx et al., 2006; Xxxxxxxxxxx et al., 2009; Xxxxxxxxxx et al., 2008; Xxxxx et al., 2009). TDP-43 is a predominantly nuclear protein that regulates mRNA expression, splicing, translation and gene transcription (Xxxxx et al., 2011). Expression of mutant TDP-43 in cells leads to an abnormal localization to the cytoplasm, particularly in stress granules (Xxx-Xxxxxxxxxx et al., 2010). Certain conditions such as oxidative stress or ischemia trigger a global translational silencing and the formation of stress granules, cytoplasmic aggregates which transiently sequester mRNA and RNA binding proteins and can modulate the signalling balance between apoptosis and survival (Xxxxxx et al., 2011). More than 6000 TDP-43 RNA targets have now been identified and these include several that are linked to ALS such as FUS, EAAT1, progranulin and TDP-43 itself (Polymenidou et al., 2011; Xxxxxxx et al., 2011; Xxxxxxxxx et al., 2011). In a similar manner to TDP-43, ALS mutant FUS shows abnormal cytoplasmic localization and can induce the formation of FUS containing cytoplasmic stress granules (Xxxxxxx et al., 2010; Xxx et al., 2011a; Xxxxxxxxxxx et al., 2009; Xxxxx et al., 2009). FUS is also a component of mRNA transporting granules and might contribute to mRNA shuttling to synapses for local translation (Xxxxx et al., 2004). Recently, FUS has been shown to facilitate exon 10 skipping in the gene encoding Tau (Xxxxxxxx et al., 2012). This generates 3-repeat Tau, an isoform which is relatively increased in neurodegenerative disorders (Xxxxxxx, 2006). In addition, TDP-43 and FUS interact to regulate mRNA expression of histone deacetylase 6 (HDAC6) (Xxx et al., 2010b), a protein involved in autophagy and stress granule formation (d'Ydewalle et al., 2012). Lastly, a GGGGCC hexanucleotide repeat expansion in a non-coding region of C9ORF72 is currently the most common ...
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Related to Damage to mRNA metabolism

  • Infectious Diseases The Employer and the Union desire to arrest the spread of infectious diseases in the nursing home. To achieve this objective, the Joint Health and Safety Committee may review and offer input into infection control programs and protocols including surveillance, outbreak control, isolation, precautions, worker education and training, and personal protective equipment. The Employer will provide training and ongoing education in communicable disease recognition, use of personal protective equipment, decontamination of equipment, and disposal of hazardous waste.

  • Influenza Vaccine Upon recommendation of the Medical Officer of Health, all employees shall be required, on an annual basis to be vaccinated and or to take antiviral medication for influenza. If the costs of such medication are not covered by some other sources, the Employer will pay the cost for such medication. If the employee fails to take the required medication, she may be placed on an unpaid leave of absence during any influenza outbreak in the home until such time as the employee has been cleared by the public health or the Employer to return to the work environment. The only exception to this would be employees for whom taking the medication will result in the employee being physically ill to the extent that she cannot attend work. Upon written direction from the employee’s physician of such medical condition in consultation with the Employer’s physician, (if requested), the employee will be permitted to access their sick bank, if any, during any outbreak period. If there is a dispute between the physicians, the employee will be placed on unpaid leave. If the employee gets sick as a reaction to the drug and applies for WSIB the Employer will not oppose the application. If an employee is pregnant and her physician believes the pregnancy could be in jeopardy as a result of the influenza inoculation and/or the antiviral medication she shall be eligible for sick leave in circumstances where she is not allowed to attend at work as a result of an outbreak. This clause shall be interpreted in a manner consistent with the Ontario Human Rights Code.

  • Biological Samples If so specified in the Protocol, Institution and Principal Investigator may collect and provide to Sponsor or its designee Biological Samples (“Biological Samples”). 12.2.

  • Infectious Disease Where an employee produces documentary evidence that:

  • DAMAGE TO FACILITIES The Student will promptly report damages and request necessary repairs, in accordance with established and published procedures. The Student is responsible for damages caused by the Student. Damages to shared or common areas not attributable to a responsible person are the joint responsibility of all persons sharing the space or area. UCF DHRL reserves the right to charge the Student for damages caused by the Student. Charges may include, but are not limited to, extraordinary pest control charges, repair of walls, furniture or fixtures, and damages to common areas. UCF DHRL also reserves the right to charge the Student for a portion of damages caused to spaces shared by the Student when the person responsible for damages to shared spaces cannot be identified.

  • Damage to Property Exhibitor is liable for any damage caused to building floors, walls or columns, or to standard booth equipment, or to other Exhibitor’s property. Exhibitor may not apply paint, lacquer, adhesives, or other coating to building columns and floors or to standard booth equipment.

  • Damage to Equipment The Parties shall exercise all necessary precautions to avoid causing damage to the other Party’s poles and Equipment and other pole attachers’ Equipment and shall assume responsibility to each other for any and all loss from any damage to the other Party’s poles or Equipment and reimburse the other Party for the entire expense incurred in making such repairs. Each Party shall assume responsibility to third parties for any and all loss from any damage caused to third party’s Equipment by such Party and shall reimburse such third party for the entire expense incurred in making repairs.

  • Hepatitis B Vaccine Where the Hospital identifies high risk areas where employees are exposed to Hepatitis B, the Hospital will provide, at no cost to the employees, a Hepatitis B vaccine.

  • Dangerous Goods, Special Wastes, Pesticides and Harmful Substances Where employees are required to work with or are exposed to any dangerous good, special waste, pesticide or harmful substance, the Employer shall ensure that the employees are adequately trained in the identification, safe handling, use, storage, and/or disposal of same.

  • Smoke Free Environment The Lessor shall make all parts of the leased premise smoke-free. "

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