CHARACTERIZATION OF THE UBIQUITIN LIGASE, UBE4B, IN ENDOCYTIC TRAFFICKING

Endocytosis is a process by which cells internalize membrane proteins to remove them from the plasma membrane, allowing cells to regulate the cell surface expression of transmembrane proteins. In this manner, cellular responses to extracellular cues may be tuned by limiting the number of proteins available at the cell surface. One particular class of proteins, receptor tyrosine kinases (RTK), is internalized upon binding to extracellular ligands during their residence at the cell surface. The epidermal growth factor receptor (EGFR) is an RTK whose trafficking through the endocytic pathway through the cell is well-documented. Stimulation of EGFR with its cognate ligand, EGF, prompts EGFR entry into the endocytic pathway and simultaneously activates downstream signal transduction pathways that regulate physiological responses, such as survival, proliferation, and differentiation. Activated EGFRs continue to signal as they traverse the endocytic pathway until the ligand-receptor complex is included into vesicles that bud into the lumen of the multivesicular body (MVB). Inclusion into internal MVB vesicles designates EGFR for lysosomal proteolysis and extinguishes their signaling activity. Ubiquitination is a post-translational modification that underlies some aspects of membrane protein trafficking. Ubiquitin modification allows EGFR recognition by endosomal protein complexes that mediate protein inclusion into MVB vesicles from those that remain on the MVB membrane for incorporation into other cellular structures (e.g. plasma membrane, Golgi). The endosomal sorting machinery consists of a core group of cytosolic proteins that are recruited to the endosomal membrane, called the endosomal sorting complexes required for transport (ESCRT) machinery. A subset of ESCRT proteins bind directly to ubiquitin, allowing the sorting machinery to engage and manipulate the movement of protein cargo into inwardly budded MVB vesicles. Lack of a ubiquitin tag precludes EGFR from inclusion into vesicles that bud into the lumen of the MVB. The precise nature of coordination between the cellular machineries that govern ubiquitination and endosomal sorting are not well understood. I have identified a protein interaction between UBE4B, an E3/E4 ubiquitin ligase, and the ESCRT-0 components, Hrs and STAM. ESCRT-0 is the first complex of the endosomal sorting machinery to bind to endosomes, and recognition by ESCRT-0 is required for EGFR sorting and degradation. Immunoprecipitation and ubiquitination assays revealed that UBE4B binds and can ubiquitinate the EGFR. Depletion of UBE4B resulted in impaired EGFR inclusion into inwardly-budded MVB vesicles. EGFR inclusion was rescued more efficiently with the addition of recombinant UBE4B versus the addition of a ubiquitination-defective mutant, UBE4B(P1140A). These data suggest that the ubiquitination of EGFR by UBE4B is required for efficient EGFR sorting. Altering UBE4B expression in neuroblastoma cells revealed a negative correlation between UBE4B expression and proliferation, as well as altered proliferative responses to EGR inhibitors. These findings suggest a mechanism by which UBE4B may regulate cell proliferation, and reveals UBE4B as a potential target in neuroblastoma therapeutic development

Effective College Transition Planning for Students with Learning Disabilities: What Does the Research Tell Us?

Kosine presents a brief overview and analysis of the article, Effects of a self-esteem intervention program on school-age children, originally published in Pediatric Nursing. The author presents a summary of the key components of the article including the introduction, method and results of the study. They offer an additional analysis of implications for future practice, including a discussion of the importance of joining between high school personnel, college personnel and the student to determine to dos and goals in order to achieve the best outcomes

Umphlett QCI March 2019

Highlights for the Basin Temperature Anomalies Plains Snowpack Agriculture Energy Transportation Temperature Precipitatio

Ambient Rivers Monitoring in NH Coastal Watersheds 2004

The Department of Environmental Services (DES) received funding from the New Hampshire Estuaries Project (NHEP) to conduct monitoring activities in 2004. The activities described in this report were led by the DES Watershed Assistance Section and involved water monitoring in tidal tributaries. These monitoring activities were completed with the overall purpose of improving the understanding of water quality trends. The Department of Environmental Services completed all tasks as planned. This report includes the sample collection information, field data, and laboratory data. Data summaries and interpretations will come at a later time in other DES and NHEP publications

The Role of School Counselors in Serving Students with Disabilities

Kosine presents a brief overview and analysis of the article, Students with disabilities: School counselor involvement and preparation, originally published in Professional School Counseling. The author presents a summary of the key components of the article including the introduction, method and results of the study. They offer an additional analysis of implications for future practice including a discussion of what school counselors need to advocate for in order gain competency in dealing with students with disabilities

The Relationship Between Community Dwelling Older Adult’s Fall Risk and Beliefs of Risk for Falling in Northwest Arkansas and Bolgatanga, Ghana.

Title: The Relationship Between Community Dwelling Older Adult’s Fall Risk and Beliefs of Risk for Falling in Northwest Arkansas and Bolgatanga, Ghana. Gohman, N., Patton, S., Smith-Blair, N., Agana, C.: University of Arkansas, Fayetteville, AR Background: Older adults worldwide live with comorbidities, physical and psychological changes associated with aging. Statistically, however, older adults are more likely to die as a result of falling. As the worldwide population of individuals over 65 rises, so will the possibility for injuries from falls. Much research has been published concerning fall risk prevention, but minimal research surrounding protocols and practices for protecting against falls in developing countries has been published. Purpose: Evaluate and compare the relationship between community dwelling older adult’s fall risk and their perceived risk of falling in a developed and a developing country. Methodology: The study sample consisted of 35 participants, selected at random. A mixed method approach was used. Semi-structured interviews based on constructs of the Health Belief Model measured perceived fall risk. Risk factors for falls were determined using the Center for Disease Control (CDC) STEADI fall risk assessment tool. Results: The average age of all participants was 73 years, with 30% from NW Arkansas and 70% from Ghana. Eight subjects reported falling within the past year. The majority of subjects reported their chance of falling as low. When asked about confidence level to prevent falling, mixed reactions ranging from laughing, being concerned, to being serious were documented. Many older adults realized the complications falling would have on their physical well being, as well as the increase in burden and negative emotional effect on the caregiver. There was an overall lack of knowledge by the general population of what to do to prevent falling. The biggest barrier reported by participants to prevent falling was the layout of homes and buildings, the physical outside environment, and lack of lighting to see. There was a lack of knowledge to knowing prevention strategies, as the only benefit stated was the individual would not fall. Discussion/Results: According to the results of the STEADI assessment, only 1 out of 35 participants actually passed the fall risk assessment. There is a lack of knowledge about falling, therefore individuals were confident that they could prevent falling despite results showing their high fall risk. More people were confident in Northewst Arkansas that they could prevent falls compared to Ghana. By 2050, the global population of adults over the age of 60 is expected to reach nearly 2.1 billion, with two thirds residing in developing countries. Results from this study indicate that many older adults believe that they have low chance of falling even when their risk is high. Global awareness is needed about the seriousness of falls in this population and for prevention that will reduce injury and hospital admissions

gamma-vectors of edge subdivisions of the boundary of the cross polytope

For any flag simplicial complex $\Theta$ obtained by stellar subdividing the boundary of the cross polytope in edges, we define a flag simplicial complex $\Gamma(\Theta)$ (dependent on the sequence of subdivisions) whose $f$-vector is the $\gamma$-vector of $\Theta$. This proves that the $\gamma$-vector of any such simplicial complex satisfies the Frankl-F\"{u}redi-Kalai inequalities, partially solving a conjecture by Nevo and Petersen \cite{np}. We show that when $\Theta$ is the dual simplicial complex to a nestohedron, and the sequence of subdivisions corresponds to a flag ordering as defined in \cite{ai}, that $\Gamma(\Theta)$ is equal to the flag simplical complex defined there.Comment: 18 pages, 1 figur

Umphlett QCI March 2016

Highlights for the Basin Temperature and Precipitation Anomalies Vegetation Conditions Early Signs of Spring Winter Wheat Breaks Dormancy 3-Month Precipitation and Temperature Outlooks Percent of Average Precipitation: Strong El Niño

Analysis of Humira, Electro-Acupuncture, and Pulsatile Dry Cupping on Reducing Joint Inflammation in Patients with Rheumatoid Arthritis

Humira, an anti-TNF drug aimed at decreasing inflammation in Rheumatoid Arthritis patients, can cause skin diseases from rashes to skin cancer. Humira works by blocking the chemical receptor RANKL which inhibits the production of osteoclasts. Osteoclasts are cells that attack and eat bone and cartilage therefore an inhibitory mechanism would cause inflammation.. By analyzing Humira’s effect on the human body, Humira can be compared to other treatments such as electro-acupuncture and pulsatile dry cupping to determine the viability of these alternative treatment methods in regards to their abilities to decrease inflammation in Rheumatoid Arthritis patients through blocking RANKL. An analysis of these treatment methods can also be used to determine the safest treatment method.. Under close examination of scientific journals written on studies where patients and animals were treated with Humira, acupuncture, and cupping for inflammation due to arthritis, the data collected suggests that Humira, electro-acupuncture, and pulsatile dry cupping all decrease inflammation in the joints of Rheumatoid Arthritis patients. However, acupuncture causes the least harmful side-effects, with nausea and localized tingling being the most common complaints. On the other hand, localized bruising is caused by cupping and Humira is associated to an increased risk of cancer, heart failure and liver failure. Therefore, electro-acupuncture and pulsatile dry cupping are safer alternatives to Humira for the treatment of inflammation associated with Rheumatoid Arthritis. As a result, the data collected from this review supports that acupuncture has the same therapeutic effects as Humira, but is less deleterious and an overall better treatment method to Rheumatoid Arthritis compared to Humira