Immunohistochemical Analysis of IL-1 Receptor 1 In the Discs of Patients with Temporomandibular Joint Dysfunction

Objective Temporomandibular joint dysfunction (TMD) may affect a patient’s quality of life, and one of the etiologies can be anterior disc displacement with reduction (ADDwR) and anterior disc displacement without reduction (ADDWoR). Interleukin 1 Receptor 1 (IL-1R1) is a membrane receptor that plays an important role on initiating immune and inflammatory response by binding the agonists ligands of IL-1 alpha and IL-1 beta. Therefore, the aim of this study was to evaluate, through immunohistochemical analysis, the association of IL-1R1 with TMD. Methods Thirty-nine human disc samples were collected and composed three different groups: ADDwR (n = 19), ADDwoR (n = 12), and control group (n = 8). The samples were immunostained with IL-1R1 antibody and evaluated on both quantity and intensity of staining. Results There was a statistically significant difference (p \u3c 0.05) between the control and test groups for both quantity and intensity of staining. Conclusion IL1-R1 was associated with ADDwR and ADDwoR in TMD discs of humans

Expression of Interleukin-1 and Temporomandibular Disorder: Contemporary Review of the Literature

Objective: Temporomandibular disorders (TMD) are a group of conditions affecting the temporomandibular joint (TMJ), leading to jaw dysfunction, joint and muscle pain, and a decrease in quality of life. A communication network of pro- and anti-inflammatory mediators called cytokines maintains the homeostasis of the TMJ. This review will focus on the Interleukin (IL) family of cytokines, which have been quantified in TMJ synovial fluids in a variety of studies. IL-1α and IL-1β have pro-inflammatory effects, while the endogenous receptor antagonist (IL-1RA) inhibits the pro-inflammatory effects of IL-1. Methods: A literature search (2006–2016) to identify eligible studies was completed using the PubMed database. Studies identified used saline irrigation to quantify cytokine profiles in synovial fluid of healthy and/or dysfunctional joints. Results: The initial search yielded 111 articles, 5 of which met the inclusion criteria after inter-reviewer discussion. Conclusions: Articles that compared IL-1 concentrations in TMD vs. control groups found significant differences

Immunohistochemical Expression of TLR-4 in Temporomandibular Joint Dysfunction

Objective Toll-like receptor 4 (TLR-4) is a transmembrane protein involved in the innate immune system and has been implicated in the pathogenesis of temporomandibular joint dysfunction (TMD). The purpose of this study was to histologically examine the level of expression of TLR-4 relative to severity of TMD. Methods Thirty-one human TMJ disc samples were immunostained for TLR-4 and evaluated for intensity of stain. Among the samples, 8 were control samples, 16 were from patients with anterior disc displacement with reduction (ADDwR), and 7 were from patients with anterior disc displacement without reduction (ADDwoR). Results There was no statistically significant difference in intensity of stain between groupings (p = 0.673). Conclusions The results indicate a negative correlation between TMD and the expression of TLR-4

Free Re-boost Electrodynamic Tether on the International Space Station

The International Space Station (ISS) currently experiences significant orbital drag that requires constant make up propulsion or the Station will quickly reenter the Earth's Atmosphere. The reboost propulsion is presently achieved through the firing of hydrazine rockets at the cost of considerable propellant mass. The problem will inevitably grow much worse as station components continue to be assembled, particularly when the full solar panel arrays are deployed. This paper discusses many long established themes on electrodynamic propulsion in the context of Exploration relevance, shows how to couple unique ISS electrical power system characteristics and suggests a way to tremendously impact ISS's sustainability. Besides allowing launch mass and volume presently reserved for reboost propellant to be reallocated for science experiments and other critically needed supplies, there are a series of technology hardware demonstrations steps that can be accomplished on ISS, which are helpful to NASA s Exploration mission. The suggested ElectroDynamic (ED) tether and flywheel approach is distinctive in its use of free energy currently unusable, yet presently available from the existing solar array panels on ISS. The ideas presented are intended to maximize the utility of Station and radically increase orbital safety

Modeling cancer genomic data in yeast reveals selection against ATM function during tumorigenesis

The DNA damage response (DDR) comprises multiple functions that collectively preserve genomic integrity and suppress tumorigenesis. The Mre11 complex and ATM govern a major axis of the DDR and several lines of evidence implicate that axis in tumor suppression. Components of the Mre11 complex are mutated in approximately five percent of human cancers. Inherited mutations of complex members cause severe chromosome instability syndromes, such as Nijmegen Breakage Syndrome, which is associated with strong predisposition to malignancy. And in mice, Mre11 complex mutations are markedly more susceptible to oncogene- induced carcinogenesis. The complex is integral to all modes of DNA double strand break (DSB) repair and is required for the activation of ATM to effect DNA damage signaling. To understand which functions of the Mre11 complex are important for tumor suppression, we undertook mining of cancer genomic data from the clinical sequencing program at Memorial Sloan Kettering Cancer Center, which includes the Mre11 complex among the 468 genes assessed. Twenty five mutations in MRE11 and RAD50 were modeled in S. cerevisiae and in vitro. The mutations were chosen based on recurrence and conservation between human and yeast. We found that a significant fraction of tumor-borne RAD50 and MRE11 mutations exhibited separation of function phenotypes wherein Tel1/ATM activation was severely impaired while DNA repair functions were mildly or not affected. At the molecular level, the gene products of RAD50 mutations exhibited defects in ATP binding and hydrolysis. The data reflect the importance of Rad50 ATPase activity for Tel1/ATM activation and suggest that inactivation of ATM signaling confers an advantage to burgeoning tumor cells

Psychological symptoms

Psychological symptoms are highly prevalent in people requiring palliative care. They are much more challenging to elicit, and more controversy exists about what is normal and what might require intervention than physical symptoms. There are significant issues in determining what is normal and what is not. Sadness, distress, anxiety, and depression can coexist and require careful assessment. Management of psychological symptoms and conditions can broadly be considered in terms of non-pharmacological and pharmacological therapies, “the talking and the drug therapies.” These are not mutually exclusive, and for people with limited energy, failing cognition, and limited time, some pragmatic decisions may be necessary. To be distressed and immobilized by emotion is not normal. Depression is not a normal part of dying. There should be discussion about the nature of psychological issues and conditions, explanation of common somatic symptoms, and a plan for intervention and support. The burden on the carer, both professional and personal, in such situations should not be underestimated.Gregory B. Crawfor

The Role of Nej1-Lif1 in Double Strand Break Repair Pathway Choice and Non-Homologous End-Joining

DNA Double strand breaks (DSBs) are the most deleterious form of DNA damage. Improper repair of DSBs can result in genomic instability and failed repair of even a single DSB results in cell death. Homologous recombination (HR) and Non-homologous end-joining (NHEJ) are the two major pathways of DSB repair and both are highly conserved from yeast to mammals. The choice between these pathways is largely based on 5’ to 3’ resection of DNA at the break site. Resection inhibition favours NHEJ, while extensive resection facilitates HR. The MRX complex, which plays a role in both HR and NHEJ in yeast, promotes the initiation of end-resection at the broken ends, while YKu70/80 rapidly binds DSB ends to prevent the initiation of 5’resection. Nej1 and Lif1 are two NHEJ proteins shown previously to promote the ligation of DSB ends by stimulating Dnl4 ligase activity. The Nej1-Lif1 interaction is also required for additional functions in NHEJ, except these functions were previously uncharacterized. Using nej1-F335A and nej1-V338A mutants that are unable to interact with Lif1, I show that the Nej1-Lif1 interaction plays a role in preventing end-resection initiation at broken ends in a manner epistatic with YKu70/80. Specifically, I demonstrate that Nej1-Lif1 prevents the Sgs1-Dna2 dependent initiation of end-resection to promote NHEJ pathway choice. I also show that the Nej1-Lif1 interaction plays a role in preventing genomic stability during DSB repair in a redundant manner with the end-bridging function of the Rad50 subunit of the MRX complex. Finally, the effect of Rad50 and Nej1 mutants on the nuclear periphery re-location of persistent DSB ends to either Mps3 or the nuclear pore complex (NPC) were studied. I show that cells lacking RAD50 absolutely require the NPC to survive even endogenous DNA damage, while cells harboring nej1Δ, yku70Δ, nej1-F335A or nej1-V338A mutants preferentially require Mps3 to promote cell survival and prevent genomic instability during the repair of persistent DSBs

NACA Research Memorandums

Report presenting a measurement of the magnitudes of pressure fluctuations in the turbulent wakes of restrained two-dimensional airfoils at transonic speeds. Measurements indicated that the total-pressure fluctuations occurred only within the wake. Results regarding the magnitude of pressure oscillation in the wake, effect stream-angle fluctuations in the wake, and frequencies of pressure oscillation on the wing and in the wake are provided