Walton County School District

Crystallography has a wide range of applications in research, but this field is rarely discussed in primary and secondary school classrooms. While it is difficult to do cutting-edge, cancer-curing research in a high school laboratory, the intricacies of crystallography can still be introduced to students of any age. Through the Structural Nucleic Acid Anticancer Research Society (STARS), we have been able to help provide educational experiences and opportunities with crystal-growing and crystallography for students grades K-12th.At the high school level, STARS has organized weekly club meetings to work with students in growing and experimenting with inorganic crystals. Students choose the best, most unique crystals of the ones they have grown to submit to the U.S. Crystal Growing Competition. Having this opportunity provides students with foundational knowledge of crystallography and can excite students about science, thus inspiring a new generation of scientists.Beyond weekly meetings, high school STARS has also worked in conjunction with the collegiate STARS branch to offer crystallography workshops and camps. Through the workshops we provide students with the opportunity to experience wet lab research with lysozyme and gain a greater understanding of crystallography and its applications. Through the summer camp, which we hosted July 1-4, 2024, we allowed younger students to grow their own inorganic crystals and learn more about the science behind crystallography and its applications. Not only was it an educational experience for the students attending the camp, but it also a valuable opportunity for members of the high school STARS group to practice public speaking and science communication, both of which are valuable skills in a variety of professions.STARS will continue to provide valuable lab experience through club meetings, workshops, camps, and more. We hope to continue to provide K-12th students with educational experiences that will help inspire the young scientists that are the future of this field of study.

The ACVRL1 gene is highly expressed in endothelial cells and encodes the transmembrane protein activin receptor-like kinase 1 (ALK1), which is a type I cell-surface receptor serine/threonine kinase for the transforming growth factor-β (TGF-β) superfamily of ligands BMP9/GDF2 and BMP10. ALK1 comprises of an extracellular ligand-binding domain, a transmembrane domain, and an intracellular kinase domain. Upon ligand binding, this receptor forms complexes with other TGF-β receptors, primarily BMP9 to activate intracellular downstream signaling pathways. The Smad pathway functions to regulate gene expression through transmitting nucleus signals from the TGFβ receptors. Signaling is transmitted by a cytoplasmic kinase domain of ALK1 by phosphorylating receptor-regulated Smad proteins (R-Smad proteins). Activated R-Smad proteins and the common-Smad (co-Smad) form a complex to regulate transcription of target genes together with cofactors. This pathway is essential for angiogenesis and vasculogenesis and a mutation can induce several vascular diseases. The Smad Pathway is also crucial for endothelial cell differentiation and homeostasis, which plays roles in Crohn's Disease. Differing mutations in the ACVRL1 gene can result in increased or decreased kinase activity as well as impaired ligand binding, disrupting of TGF-β signaling, and in some cases induce a rare genetic disorder known as Hereditary Hemorrhagic Telangiectasia (HHT). HHT is an inherited disorder characterized by abnormally formed blood vessels. TGF-β can act as both a tumor suppressor and a tumor promoter, and mutations or dysregulation of components in its pathway can lead to several types of cancer. In Crohn's disease patients, scientists were able to determine an increased risk of endoscopic relapse based on ALK1 levels. Additionally, activation of ALK1 has been shown to enhance colonic intestinal epithelial barrier integrity and function ex vivo in these studies. The Walton High School SMART team, with support from 3D molecular designs, has modeled ALK1 receptors to support testing of the ALK1 protein to develop potential therapies and interventions for Crohn's disease, HHT, and several cancers.

RUVBL1 and RUVBL2 are two highly conserved eukaryotic AAA+ (ATPases Associated with diverse cellular Activities) proteins that engage in a diverse array of cellular functions. These functions can range from ribonucleoprotein complex assembly and cellular transformation to chromatin remodeling and DNA damage response. Individually, RUVBL1 and RUVBL2 form homohexamers with weak ATPase activities. However, together they form highly active heterohexameric or dodecameric complexes made up of alternating units of RUVBL1 and RUVBL2. Like all other AAA+ proteins, RUVBL1 and RUVBL2 ATPases contain a Walker A and a Walker B motif. These motifs are required for nucleotide binding and hydrolysis, respectively. RUVBL1 and RUVBL2 are each made up of three distinct domains: an N terminal αβα subdomain of the AAA+ domain, a 170 amino-acid insertion domain, and an all α subdomain of the AAA+ domain. The amino-acid insertion domain is unique to RUVBL1 and RUVBL2 and can mediate DNA or RNA binding. Despite its many essential functions, the complex of RUVBL1 and RUVBL2 (referred to as RUVBL1/2 here) is present at low levels in eukaryotic cells. It is therefore thought that RUVBL1/2 interacts only transiently with its binding partners and acts as a chaperone for assembly of other complexes. The molecular mechanism by which the RUVBL1/2 ATPase engages in cellular activities remains elusive. Interestingly, RUVBL1/2 is overexpressed in numerous human cancers including gastric, bladder, pancreatic, and breast cancers. For example, researchers have found that in pancreatic ductal adenocarcinoma (PDAC), which is among the deadliest cancers, RUVBL1 helps the formation of membrane protrusions by promoting actin polymerization. These protrusions increase the invasiveness and metastatic properties of PDAC cells. Due to their strong link to oncogenesis, design of inhibitors against RUVBL1/2 is a major area of research. Although members of the AAA+ family are challenging drug targets, recent high-resolution structures and new drug screening strategies have enabled advances in design of novel AAA+ inhibitors. For example, the small molecules Sorafenib and CB-6644 were recently reported to inhibit the ATPase activity of the RUVBL1/2 complex. With further optimizations and testing, these drugs may be improved and potentially considered as potent therapeutic inhibitors of RUVBL1/2 activity. The Walton SMART team has designed a 3D model of RUVBL1/2 to investigate the relationship between the molecular structure and function of this ATPase complex.

Analyze intrarater and interrater reliability for evaluating endoscopic images of velopharyngeal (VP) physiology. Speakers produced 9 speech stimuli representing 4 stimulus types: sustained phonemes, repetitions of "puh," single words, and short phrases. The 37-speaker participants included 16 patients with VP dysfunction and 21 control participants. Five raters independently rated the video images for degree of VP opening, location of opening, and pattern of closure. Outcome measures included intrarater and interrater measures of reliability and the effects of raters and stimulus type on ratings. Intrarater reliability was acceptable, and ratings were logically consistent. Fixed effects regression coefficients for the patient and the control groups showed that raters were a significant source of variability for degree of opening and pattern of closing. Stimulus type was not a significant source of variation for any metric for the controls, but stimulus type was a significant determinant for degree of opening for patients. The degree of opening was larger for sustained phonemes than for the other speech stimuli. Ratings for degree of opening were most similar for repeated "puh." Interrater reliability needs to be improved so that the assessment procedure produces more consistent findings among clinicians, thus strengthening our evidence base for this procedure. Interrater additional research is needed to understand how the stimulus affects ratings of VP physiology, to identify stimuli that yield the most useful clinical information, and to understand how training affects the ratings of VP physiology.

The ability of vertebrates, including humans, to see light relies on a visual transduction cascade in which rhodopsin’s ability to stimulate the nervous system plays a central role. Rhodopsin is a 348 amino acid protein composed of seven transmembrane alpha helices located within the rod photoreceptor cells of the retina. Rhodopsin is a member of the much broader protein superfamily, the G‐protein coupled receptors (GPCRs). GPCRs are cell surface signaling receptors that convert extracellular signals into intracellular signaling pathways through the activation of G proteins. There are about 800 different human GPCRs and members of this superfamily are responsible for our sense of smell, taste, and vision. The “wild type” rhodopsin uses its retinal pigment, a derivative of vitamin A, in conjunction with its G protein partner, transducin, to detect light, particularly in night vision. Retinal serves as the “cofactor” of rhodopsin that directly absorbs a photon, causing its isomerization and a change in the structure of rhodopsin that is sensed by transducin, leading to an intracellular signaling cascade that results in a signal being sent through the optic nerve to the brain that light has been detected. Any one of over 150 rhodopsin mutations already documented in humans are known to result in loss of rhodopsin’s light‐sensing function, leading to Retinitis Pigmentosa (RP). RP is a rare, slow, progressive, genetic disease which damages the retina leading to loss of vision, particularly among young adults. The most common cause of RP is a mutation‐induced misfolding of rhodopsin. The many forms of proposed treatment of RP are largely focused on improving folding of rhodopsin and inducing proteostasis, the process in the cell that promotes correct folding and quantities of proteins. Pharmacological chaperones, such as retinoids or non‐isomerrizable retinoid analogues directly target protein structure and have produced lab results that show enhanced folding and protection of other cells from the effects of mutated rhodopsin. However, replicating this in living organisms has not been possible yet. Nutritional supplements, histone deacetylase inhibitors, such as Valproate, and molecular chaperone inducers have also been tested, but only produce laboratory results that positively affect only a few aspects of mutated rhodopsin and have not yet yielded promising results in humans. Seemingly, the most promising forms of treatment for RP and rhodopsin mutations are gene therapy and CRISPR Cas‐9 genome editing to correct the genetic defects that underlie RP. However, whether any of these approaches will eventually form the basis for effective treatment or cure of RP is not yet known. The Walton High School MSOE Center for Biomolecular Modeling SMART Team has designed a 3‐D model of rhodopsin to further investigate and examine the structure‐function relationship of the protein.Support or Funding InformationMSOE Center for Biomolecular Modeling

ABSTRACT The purpose of this study was to explore high school teachers’ perceptions about principal leadership practices, as well as to gain an understanding of the teachers’ perceptions of school climate in a large urban district in the Western United States. Data were collected with two surveys, the Leadership Practices Inventory and the Organizational Climate Description Questionnaire Revised for Secondary Schools, along with five demographic questions including age, gender, number of years teaching, number of years teaching with current principal, and level of education. Across nine high schools, 334 completed surveys were used to examine relationships among variables within the instruments, as well as to explore possible differences by demographic variables. Teachers who were older within the school setting perceived themselves as being less engaged and intimate, as related to the school climate, while those with principals for a shorter amount of time and only a bachelor’s degree (perhaps more novice) perceived the principals’ practices more positively. Results also suggested that, in schools where teachers perceived their principal as carrying out the given leadership practices, higher levels of a positive school climate were also perceived among higher-performing schools and within schools higher levels of federal free and/or reduced lunch rates.

Tumor necrosis factor‐alpha (TNF‐α) is a 233 amino acid, 17 kilodalton, homotrimer, bell‐shaped proinflammatory cytokine. TNF‐α is usually secreted from monocytes and macrophages and is also an inducer of many proinflammatory cytokines like IL‐1, IL‐6 and others to help regulate immune cell function. . TNF‐α has two transmembrane cell receptors, TNF‐R1 and TNF‐R2, which have functional binding domains located on the outside of the cell and catalytic signaling domains located inside the cell. TNF‐R1 mediates the activation of a number of transcription factors resulting in an increased inflammatory response, while TNF‐R2 increases the number of T‐cells through a proliferation/survival pathway. A high amount of TNF‐α compared to a low number of its receptors leads to joint inflammation and eventual shock, while a low amount of TNF‐α leads to cachexia. Rheumatoid Arthritis (RA) has many causes including environmental factors, proclivity of smoking, or a genetic history, but in all cases, TNF‐α seems to play a role in disease progression due to its high proteins concentration in advanced disease stages. The source of TNF‐α in joints could be due to the production of the protein by CD4+ T cells in the synovial fluid which has been associated with synoviocyte proliferation, osteoclast activation, and cartilage degradation. Attempts to inhibit TNF‐α are currently centered around general suppression of the protein through TNF‐α inhibitors, but due to the devastating effects these treatments have on the immune system, further studies are considering creating higher numbers of anti‐inflammatory cytokines to create a balance between inflammatory and anti‐inflammatory cytokines, while other studies are attempting to target downstream protein targets of TNF‐α in an attempt to selectively suppress disease symptoms. The Walton High School SMART Team has designed a 3D model of TNF‐α using JMOL to investigate the relationship between structure and function.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

The loss of the neurotransmitter dopamine (DA) in the substantia nigra, the part of the brain controlling motility, has been associated with Parkinsonʼs Disease (PD) but there has been little evidence to show what causes the loss of DA. New research indicates a relationship between a drop in DA and the presence of Lewy bodies, which include aggregates of a misfolded protein, alpha‐synuclein (α‐syn). Research indicates that α‐syn is a 140 amino acid protein involved in the exocytosis of DA from the synaptic vesicles of neurons. α ‐syn has an identifiable sequence (KTKEGV) that repeats six times at the N‐terminus, which folds a normal protein into amyloid fibers. Mutations, like A53T, A30P, and E46K, or exposure to environmental factors modify the normal quaternary structure of the protein, initiating the aggregation of misfolded α‐syn. The build‐up of abnormal α‐syn highly correlates with the drop in dopamine levels in the brain, which is associated with motor dysfunction in PD patients. The Walton SMART Team (Students Modeling A Research Topic) used 3D printing techniques to see how mutated α‐syn correlates with DA levels.Grant Funding Source: Supported by grants from NIH‐CTSA and NIH‐SEPA.

Frontline youth workers’ ability to form strong, positive relationships with program youth is a key element in maximizing the benefits of program participation. A recent National Collaboration of Youth (2006) report identified six elements associated with youth workers’ competency to complete their professional roles: compensation, training opportunities, supportive work environment, clear work roles, sense that work is valued, and networking opportunities. The current study investigated whether having these elements predicted 459 youth workers’ self-reported job competency in forming positive relationships with youth. Regression analyses revealed that job efficacy, clarity of work roles, and benefits significantly predicted competency in forming strong relationships with program youth. Findings are discussed in relation to practice implications for the youth work field.

This study compared the language behaviours of parents of toddlers with language delay (LD) and language ofparents of typically developing toddlers (LN). Results indicate that parents of children with a language delay and children with normal language produced comparable amounts of linguistic input, but differed on some qualitative measures. Parents of children with normal language used more responses, expansions and self-directed speech than parents of toddlers with language delay. Parents may adjust their conversational style to the communicative ability of their children. These results reinforce language behaviours taught in parent training programmes.