Peril, Pandemic, and Crisis: Asian American Studies

Hello and Welcome to our Zine!! We are so happy you stopped by! :) We were presented the opportunity to create a zine on Asian American studies through Josen Diaz’s ETHN course. Although this started out as a project, it became so much more to our group. We had the opportunity to explore different Asian American cultures, their history, and their influence on American culture and politics. This project allowed us to relate all of the historical readings from the Chinese Exclusion Act and the world wars to events that occur today. Over the semester, we developed our overall knowledge on ethnic studies and expanded worldviews; we hope that reading this zine will allow you to do the same. In this document, we attempted to construct a creative medium which conveys all of our thoughts and ideas on the subject matter at hand. The three of us are juniors at the University of San Diego studying under varying disciplines. We all come from different parts of California and brought different perspectives to the table when brainstorming and working on the zine each week. Before reading this Zine, we want all readers to understand that the opinions and viewpoints shared here are our subjective views relating to academic texts. We are by no means authorities on these topics, and we encourage you to do your own research to expand your personal knowledge. This is a great place to begin or continue one\u27s academic journey into Asian American studies, but it is not intended to be used as a basis of knowledge or a foundational source. We hope that you all enjoy reading this zine and find its contents interesting and informative.https://digital.sandiego.edu/ethn-zines/1004/thumbnail.jp

Self-acetylation at the active site of phosphoenolpyruvate carboxykinase (PCK1) controls enzyme activity

Acetylation is known to regulate the activity of cytosolic phosphoenolpyruvate carboxykinase (PCK1), a key enzyme in gluconeogenesis, by promoting the reverse reaction of the enzyme (converting phosphoenolpyruvate to oxaloacetate). It is also known that the histone acetyltransferase p300 can induce PCK1 acetylation in cells, but whether that is a direct or indirect function was not known. Here we initially set out to determine whether p300 can acetylate directly PCK1 in vitro. We report that p300 weakly acetylates PCK1, but surprisingly, using several techniques including protein crystallization, mass spectrometry, isothermal titration calorimetry, saturation-transfer difference nuclear magnetic resonance and molecular docking, we found that PCK1 is also able to acetylate itself using acetyl-CoA independently of p300. This reaction yielded an acetylated recombinant PCK1 with a 3-fold decrease in kcat without changes in Km for all substrates. Acetylation stoichiometry was determined for 14 residues, including residues lining the active site. Structural and kinetic analyses determined that site-directed acetylation of K244, located inside the active site, altered this site and rendered the enzyme inactive. In addition, we found that acetyl-CoA binding to the active site is specific and metal dependent. Our findings provide direct evidence for acetyl-CoA binding and chemical reaction with the active site of PCK1 and suggest a newly discovered regulatory mechanism of PCK1 during metabolic stress

Association between the LRP1B and APOE loci in the development of Parkinson’s disease dementia

Parkinson’s disease is one of the most common age-related neurodegenerative disorders. Although predominantly a motor disorder, cognitive impairment and dementia are important features of Parkinson’s disease, particularly in the later stages of the disease. However, the rate of cognitive decline varies among Parkinson’s disease patients, and the genetic basis for this heterogeneity is incompletely understood. To explore the genetic factors associated with rate of progression to Parkinson’s disease dementia, we performed a genome-wide survival meta-analysis of 3923 clinically diagnosed Parkinson’s disease cases of European ancestry from four longitudinal cohorts. In total, 6.7% of individuals with Parkinson’s disease developed dementia during study follow-up, on average 4.4 ± 2.4 years from disease diagnosis. We have identified the APOE ε4 allele as a major risk factor for the conversion to Parkinson’s disease dementia [hazard ratio = 2.41 (1.94–3.00), P = 2.32 × 10−15], as well as a new locus within the ApoE and APP receptor LRP1B gene [hazard ratio = 3.23 (2.17–4.81), P = 7.07 × 10−09]. In a candidate gene analysis, GBA variants were also identified to be associated with higher risk of progression to dementia [hazard ratio = 2.02 (1.21–3.32), P = 0.007]. CSF biomarker analysis also implicated the amyloid pathway in Parkinson’s disease dementia, with significantly reduced levels of amyloid β42 (P = 0.0012) in Parkinson’s disease dementia compared to Parkinson’s disease without dementia. These results identify a new candidate gene associated with faster conversion to dementia in Parkinson's disease and suggest that amyloid-targeting therapy may have a role in preventing Parkinson’s disease dementia

Global chemical effects of the microbiome include new bile-acid conjugations

A mosaic of cross-phylum chemical interactions occurs between all metazoans and their microbiomes. A number of molecular families that are known to be produced by the microbiome have a marked effect on the balance between health and disease. Considering the diversity of the human microbiome (which numbers over 40,000 operational taxonomic units), the effect of the microbiome on the chemistry of an entire animal remains underexplored. Here we use mass spectrometry informatics and data visualization approaches to provide an assessment of the effects of the microbiome on the chemistry of an entire mammal by comparing metabolomics data from germ-free and specific-pathogen-free mice. We found that the microbiota affects the chemistry of all organs. This included the amino acid conjugations of host bile acids that were used to produce phenylalanocholic acid, tyrosocholic acid and leucocholic acid, which have not previously been characterized despite extensive research on bile-acid chemistry. These bile-acid conjugates were also found in humans, and were enriched in patients with inflammatory bowel disease or cystic fibrosis. These compounds agonized the farnesoid X receptor in vitro, and mice gavaged with the compounds showed reduced expression of bile-acid synthesis genes in vivo. Further studies are required to confirm whether these compounds have a physiological role in the host, and whether they contribute to gut diseases that are associated with microbiome dysbiosis

Determining crystal structures through crowdsourcing and coursework

We show here that computer game players can build high-quality crystal structures. Introduction of a new feature into the computer game Foldit allows players to build and real-space refine structures into electron density maps. To assess the usefulness of this feature, we held a crystallographic model-building competition between trained crystallographers, undergraduate students, Foldit players and automatic model-building algorithms. After removal of disordered residues, a team of Foldit players achieved the most accurate structure. Analysing the target protein of the competition, YPL067C, uncovered a new family of histidine triad proteins apparently involved in the prevention of amyloid toxicity. From this study, we conclude that crystallographers can utilize crowdsourcing to interpret electron density information and to produce structure solutions of the highest quality

Magnetostratigraphy, age and depositional environment of the Lobo Formation, southwest New Mexico: implications for the Laramide orogeny in the southern Rocky Mountains

International audienceThe Lobo Formation of southwestern New Mexico consists of spatially variable continental successions attributed to the Laramide orogeny (80-40 Myr), although its age and provenance are virtually undocumented. This study combines sedimentological, magnetostratigraphical and geochronological data to infer the timing and origin of the Lobo Formation. Measured sections of Lobo strata at two locations, Capitol Dome in the Florida Mountains and in the Victorio Mountains, indicate significant differences in depositional environments and sediment provenance. At Capitol Dome, where Lobo strata were deposited above a syncline developed in Palaeozoic strata, deposition took place in fluvial, palustrine and marginal lacustrine settings, with alluvial-fan deposits only at the top of the formation. Combined magnetostratigraphy and a young U-Pb detrital zircon age suggest deposition of the section at Capitol Dome from~60 to 52 Ma. The Lobo Formation in the Victorio Mountains was deposited in alluvial-fan and fluvial settings; the age of deposition is poorly bracketed between 66 AE 2 Ma, the weighted-mean age of two young zircons, and middle Eocene (~40 Ma), the approximate age of overlying volcanic rocks. U-Pb zircon ages from sandstones at the Victorio and Capitol Dome localities indicate that different source rocks provided sediment to the Lobo Formation. Local Proterozoic basement (~1.47-1.45 Ga) dominated the source of the Lobo Formation in the Victorio Mountains, consistent with abundant granitic clasts that are present in the proximal facies there; a diverse range of grain ages suggest that recycled Lower Cretaceous strata provided the dominant source for Lobo Formation sediment at the Capitol Dome locality. The U-Pb data suggest that the depositional systems at the two sites were not connected. Contrasts in depositional setting and detrital zircon provenance indicate that the Palaeogene Lobo Formation in southwest New Mexico was deposited in an assemblage of local depositional settings, possibly in separate structural basins, as a consequence of Laramide tectonics in the region

SmgGDS-607 Regulation of RhoA GTPase Prenylation Is Nucleotide-Dependent

Protein prenylation involves the attachment of a hydrophobic isoprenoid moiety to the C-terminus of proteins. Several small GTPases, including members of the Ras and Rho subfamilies, require prenylation for their normal and pathological functions. Recent work has suggested that SmgGDS proteins regulate the prenylation of small GTPases <i>in vivo</i>. Using RhoA as a representative small GTPase, we directly test this hypothesis using biochemical assays and present a mechanism describing the mode of prenylation regulation. SmgGDS-607 completely inhibits RhoA prenylation catalyzed by protein geranylgeranyltransferase I (GGTase-I) in an <i>in vitro</i> radiolabel incorporation assay. SmgGDS-607 inhibits prenylation by binding to and blocking access to the C-terminal tail of the small GTPase (substrate sequestration mechanism) rather than via inhibition of the prenyltransferase activity. The reactivity of GGTase-I with RhoA is unaffected by addition of nucleotides. In contrast, the affinity of SmgGDS-607 for RhoA varies with the nucleotide bound to RhoA; SmgGDS-607 has a higher affinity for RhoA-GDP compared to RhoA-GTP. Consequently, the prenylation blocking function of SmgGDS-607 is regulated by the bound nucleotide. This work provides mechanistic insight into a novel pathway for the regulation of small GTPase protein prenylation by SmgGDS-607 and demonstrates that peptides are a good mimic for full-length proteins when measuring GGTase-I activity

IMPACT OF THE NORTH AMERICAN MONSOON ON ISOTOPE PALEOALTIMETERS: IMPLICATIONS FOR THE PALEOALTIMETRY OF THE AMERICAN SOUTHWEST

International audiencePaleoaltimetric studies have characterized in detail the relationship between carbonate oxygen isotope ratios (d18Oc) and elevation in orogens with simple, single-moisture-source hydrological systems, and applied this relationship to ancient continental carbonates to provide constraints on their past elevation. However, mixing of different atmospheric moisture sources in low-elevation orogens should affect d18Oc values, but this effect has not yet been confirmed unequivocally. In the American Southwest, summer monsoonal moisture, sourced in the Equatorial Pacific and the Gulf of Mexico, and winter moisture, sourced in the East Pacific, both contribute to annual rainfall. We present stable isotope results from Quaternary carbonates within the American Southwest to characterize the regional d18Oc-elevation relationship. We then provide stable isotope results from local Eocene carbonates to reconstruct late Laramide paleoelevations. The Quaternary d18Oc-elevation relationship in the American Southwest is not as straightforward as in more simple hydrological systems. d18Oc changes with altitude are non-linear, scattered, and display an apparent isotopic lapse rate inversion above 1200 m of elevation. We speculate that decreasing surface temperatures at high altitudes limit the duration of carbonate growth to the summer months, biasing d18Oc values toward higher values typical of the summer monsoon and leading to lapse rate inversion. d18Oc-elevation relationships based on modern water isotope data or distillation models predict paleoelevations that range up to as much as 2 km higher than the modern elevations of 2000 to 2400 m for our late Eocene sites located at the southern edge of the Colorado Plateau. By contrast, our d18Oc-elevation relationship for the American Southwest yields lower paleoelevation estimates. These alternate estimates nonetheless suggest that significant elevation (at least ϳ1 km) had already been attained by the Eocene, but are also compatible with < 1 km of uplift by post-Laramide mechanisms. Our results show the limitations of standard d18Oc-elevation models in complex hydrological systems and suggest that similar mechanisms may have led to summer-biased paleoaltimetry estimates for the initial stages of other orogenies -in the American Southwest and elsewhere

The citrate transporters SLC13A5 and SLC25A1 elicit different metabolic responses and phenotypes in the mouse

Abstract Cytosolic citrate is imported from the mitochondria by SLC25A1, and from the extracellular milieu by SLC13A5. In the cytosol, citrate is used by ACLY to generate acetyl-CoA, which can then be exported to the endoplasmic reticulum (ER) by SLC33A1. Here, we report the generation of mice with systemic overexpression (sTg) of SLC25A1 or SLC13A5. Both animals displayed increased cytosolic levels of citrate and acetyl-CoA; however, SLC13A5 sTg mice developed a progeria-like phenotype with premature death, while SLC25A1 sTg mice did not. Analysis of the metabolic profile revealed widespread differences. Furthermore, SLC13A5 sTg mice displayed increased engagement of the ER acetylation machinery through SLC33A1, while SLC25A1 sTg mice did not. In conclusion, our findings point to different biological responses to SLC13A5- or SLC25A1-mediated import of citrate and suggest that the directionality of the citrate/acetyl-CoA pathway can transduce different signals