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A fungal ubiquitin ligase and arrestin binding partner contribute to pathogenesis and survival during cellular stress
No full textCellular responses to external stress allow microorganisms to adapt to a vast array of environmental conditions, including infection sites. The molecular mechanisms behind these responses are studied to gain insight into microbial pathogenesis, which could lead to new antimicrobial therapies. Here, we explore a role for arrestin protein-mediated ubiquitination in stress response and pathogenesis in the pathogenic fungus Cryptococcus neoformans. In a previous study, we identified four arrestin-like proteins in C. neoformans and found that one of these is required for efficient membrane synthesis, likely by directing interaction between fatty acid synthases and the Rsp5 E3 ubiquitin ligase. Here, we further explore Cn Rsp5 function and determine that this single Ub ligase is absolutely required for pathogenesis and survival in the presence of cellular stress. Additionally, we show that a second arrestin-like protein, Ali2, similarly facilitates interaction between Rsp5 and some of its protein targets. Of the four postulated C. neoformans arrestin-like proteins, Ali2 appears to contribute the most to C. neoformans pathogenesis, likely by directing Rsp5 to pathogenesis-related ubiquitination targets. A proteomics-based differential ubiquitination screen revealed that several known cell surface proteins are ubiquitinated by Rsp5 and a subset also requires Ali2 for their ubiquitination. Rsp5-mediated ubiquitination alters the stability and the localization of these proteins. A loss of Rsp5-mediated ubiquitination results in cell wall defects that increase susceptibility to external stresses. These findings support a model in which arrestin-like proteins guide Rsp5 to ubiquitinate specific target proteins, some of which are required for survival during stress
Early radiographic outcomes after anterior cervical discectomy and fusion with anatomic versus lordotic cages
No full textBackground: Anterior cervical discectomy and fusion (ACDF) interbody implants are shaped anatomically, with a convex superior aspect, or lordotically, with an angle and flat surfaces. However, the effect of implant shape on cervical sagittal balance (CSB) is not well described. Methods: Of the 192 cases reviewed from 2018 to 2019, 118 were included with matching pre- and postoperative imaging. Cases were categorized by interbody implant type (anatomic or lordotic) and number of levels fused (1-level, 2-level, etc.). SurgiMap was used to measure cervical lordosis (CL), C2�C7 sagittal vertical axis (cSVA), T1 slope (T1S), and T1S minus CL (T1S-CL) on pre- and postoperative imaging. Pre- and postoperative parameters were compared within and between each cohort. Change in CL (?CL), cSVA (?cSVA), and T1S-CL (?T1S-CL) were calculated as the difference between pre- and postoperative values and were compared accordingly (1) anatomic versus lordotic and (2) 1-level versus 2-level versus 3-level fusion. Results: Thirty-nine (33.1%), 57 (48.3%), and 22 (18.6%) cases comprised the anatomic, lordotic, and mixed (anatomic and lordotic) groups, respectively. ACDFs improved CL and T1S-CL by 5.71� (p<.001) and 3.32� (p<.01), respectively. CL was improved in the lordotic (5.27�; p<.01) and anatomic (4.57�; p<.01) groups, while only the lordotic group demonstrated improvement in T1S-CL (3.4�; p=.02). There were no differences in ?CL (p=.70), ?cSVA (p=.89), or ?T1S-CL (p=.1) between the groups. Two- and 3-level fusions improved CL by 7.48� (p<.01) and 9.62� (p<.01), and T1S-CL by 4.43� (p<.01) and 5.96� (p<.01), respectively. Conclusions: Overall, ACDFs significantly improved CL and T1S-CL however, there were no differences in CSB correction between the anatomic and lordotic groups. Two- and 3-level fusions more effectively improved CL (vs. single-level) and T1S-CL (vs. 3-level). These results suggest that implants should continue to be personalized to the patient's anatomy, however, future research is needed to validate these findings and incorporate the effects of preoperative deformities
The Effect of American Intervention on Coup Occurrence in Latin America
No full textThis project seeks to add a layer of analysis to the study of political instability in Latin America. In previous research, much attention has been paid to economic and political factors as a cause of presidential instability in Latin America. The current research is thorough and important, but it leaves out external intervention by the United States as a key cause of presidential instability. Additionally, much of the current work focuses on impeachments as a means of terminating a presidency early, while this piece focuses on coups. My theory is that countries that experienced a successful American backed coup would see more coups than countries without a successful American intervention. Additionally, I theorize that countries that experienced intervention will have more coups after the intervention than before. My theory is based on the idea that a successful coup creates a domino effect that makes future coups more likely. This is because successful coups undermine democratic institutions, legitimize future coup attempts, and send a signal to future coup plotters that there is a better chance they will be successful. In my qualitative analysis, I found that successful coups embolden future coup plotters and normalize coups as a transfer of power. My quantitative analysis found that from 1950-2021, countries experiencing American intervention averaged .76 more coups than countries that did not experience an American intervention. Additionally, my analysis found that every country that experienced American intervention experienced as many as or more coups after the intervention than before. In all, my research suggests that American interventions in the region inadvertently created additional coups which has created leadership crises and continues to influence the political instability of the region today
Intramedullary nail fixation versus open reduction and internal fixation for treatment of adult diaphyseal forearm fractures: a systematic review and meta-analysis
No full textBackground Diaphyseal radius and ulna fractures require surgical fixation in adults. Open reduction and internal fixation (ORIF) have been considered the gold standard of treatment. The recent development of an interlocking intramedullary nail (IMN) has provided an alternative treatment method for these fractures. The objective of this meta-analysis is to compare the outcomes and complications of IMN versus ORIF for diaphyseal forearm fractures in adults. Methods MEDLINE and Embase were searched from January 1, 2000, through January 7, 2024. All English-language studies were included comparing radiographic and functional outcomes for interlocking IMN fixation and ORIF of diaphyseal forearm fractures in adults (age ≥ 18 years). Study demographics, fracture data, functional outcomes, radiographic outcomes, and complications were extracted. Study quality was determined using the ROBINS-I criteria for cohort studies and the Cochrane risk of bias 2.0 (RoB 2) tool for randomized controlled trials. Meta-analysis of included studies used odds ratios and standardized mean difference when appropriate. Data was analyzed using subgroups of all diaphyseal fractures (including isolated radius or ulna fractures) and those with BBFFs. Results Nine studies were included for analysis. There were 42 isolated radius, 80 isolated ulna, and 116 both-bone fractures (BBFF) treated with IMN and 36 radius, 81 ulna, and 116 both-bone fractures treated with ORIF. Compared to ORIF, IMN of diaphyseal forearm fractures appeared to be associated with shorter operative times and a lower overall complication rate. Time-to-union and the rate of nonunion following IMN were similar to ORIF. According to the Grace–Eversmann score, functional outcomes tended to be better following IMN, but DASH scores were similar between fixation strategies. Conclusions Our findings suggest that interlocking IMN can be a safe and effective treatment option for simple and complex diaphyseal forearm fractures in adults. Further high-quality studies are needed to define indications for treating diaphyseal fractures with an interlocking IMN. Level of Evidence Therapeutic Level IV. Supplementary Information The online version contains supplementary material available at 10.1186/s13018-024-05158-0
Only the Special Survive: Star Cluster Disruption in Milky Way-like Galaxy Simulations
No full textThere is currently a mismatch between the chemical fingerprint of a typical star of a given age at a particular location in the Galaxy and those within open clusters in the same area of the Milky Way. Studying open star clusters allows us to trace essential information throughout the rich history of our Galaxy, as we can measure their age and their chemical composition independently. While some open clusters interact with their environment, causing them to dissolve, a minority remains bound for billions of years. In order to investigate why some open clusters persist for a long time, we study the evolution of open clusters through time via simulations. We use galaxies drawn from the Latte suite of Milky Way-mass zoom-in cosmological simulations generated using the FIRE-2 code. This enables us to investigate where open clusters form, if and why they move from their radius of formation, and how they traverse and interact with the Galaxy over time. In this work, we focus on tracing the unique trajectories of three illustrative open clusters throughout time. In the future, we aim to compare the FIRE-2 simulation results to the observed results from the SDSS-based Open Cluster Chemical Abundance and Mapping (OCCAM) survey
Merging MaNGA and HST to Explore the Connection Between Star Formation and the Circumgalactic Medium
No full textPatterns of inflowing and outflowing gases from the circumgalactic medium (CGM) provide a method of recycling star-forming materials in the galaxy. To probe the CGM, we have selected 15 edge-on galaxies (inclination greater than 60 degrees) from the SDSS/Mapping Nearby Galaxies at Apache Point Observatory (MaNGA) project that have archival observations of a background active galactic nucleus (AGN) within 0.8 Rvir of the galaxy’s center. MaNGA observations provide spatially and kinematically resolved spectra that allow us to infer ionization properties, stellar velocities, star formation, etc. in various regions of the galaxy. We select edge-on galaxies specifically so that the projection effects from the disk are minimized when examining spectra from the background AGN. We use the Marvin Python package to provide spatially-resolved dust attenuation corrections and star-formation rates across each galaxy. We seek to characterize the CGMs with archival Hubble Space Telescope UV observations of background AGN sightlines. Absorption of the light from background AGN by the gas in the halos will provide crucial information on the composition and physical properties of the gas surrounding these galaxies. By combining MaNGA emission line and HST absorption line spectra we can gain insight into the effect the CGM has on star formation
The Open Cluster Chemical Abundances and Mapping (OCCAM) Survey: First Results from SDSS-V
No full textThe fine details of how galaxies evolve chemically and dynamically can only be probed within the Milky Way and other nearby galaxies. While studies have been done which use field stars to probe chemical variations in the Milky Way, reliable ages in these stellar samples are difficult to derive. Therefore, we aim to produce a large sample of open clusters, for which ages can be derived, to study the evolution of the Galactic disk. Open clusters are key evolution tracers, as they are groups of stars that have formed from the same gas cloud and therefore have similar properties: velocity, location, metallicity, and age. For this project, we updated the Open Cluster Chemical Abundances and Mapping (OCCAM) survey’s cluster membership pipeline, to provide improved membership samples and to incorporate new data from Gaia DR3 and the SDSS-V/Milky Way Mapper survey. Here, we provide the first sample of new open cluster membership and abundances using SDSS-V data, which will be used to explore trends in metallicity and abundance to improve our understanding of the Milky Way’s chemical evolution
Electromagnetic Source Imaging in Presurgical Evaluation of Children with Drug-Resistant Epilepsy
No full textFor children with drug-resistant epilepsy (DRE), seizure freedom relies on the delineation and resection (or ablation/disconnection) of the epileptogenic zone (EZ) while preserving the eloquent brain areas. The development of a reliable and noninvasive localization method that provides clinically useful information for the localization of the EZ is, therefore, crucial to achieving successful surgical outcomes. Electric and magnetic source imaging (ESI and MSI) have been increasingly utilized in the presurgical evaluation of these patients showing promising findings in the delineation of epileptogenic as well as eloquent brain areas. Moreover, the combination of ESI and MSI into a single solution, namely electromagnetic source imaging (EMSI), performed on simultaneous high-density electroencephalography (HD-EEG) and magnetoencephalography (MEG) recordings has shown higher source localization accuracy than either modality alone. Despite these encouraging findings, such techniques are performed in only a few tertiary epilepsy centers, are rarely recorded simultaneously, and are underutilized in pediatric cohorts. This study illustrates the experimental setup for recording simultaneous MEG and HD-EEG data as well as the methodological framework for analyzing these data aiming to localize the irritative zone, the seizure onset zone, and eloquent brain areas in children with DRE. More specifically, the experimental setups are presented for (i) recording and localizing interictal and ictal epileptiform activity during sleep and (ii) recording visual-, motor-, auditory-, and somatosensory-evoked responses and mapping relevant eloquent brain areas (i.e., visual, motor, auditory, and somatosensory) during visuomotor task, as well as auditory and somatosensory stimulations. Detailed steps of the data analysis pipeline are further presented for performing EMSI as well as individual ESI and MSI using equivalent current dipole (ECD) and dynamic statistical parametric mapping (dSPM)
Retenes fronterizos: un análisis retórico
No full textMigration shapes the US-Mexico border, which leads to an oversaturated presence of US Border Patrol. At the interior border checkpoint, Border Patrol agents stop vehicles, interrogate drivers and passengers on citizenship status, and inspect these vehicles and occupants. I frame the interior border checkpoint as a metonym of warfare at the border via immigration enforcement to investigate the contentious yet symbiotic relationship between citizenship and enemyship. During rhetorical exchanges at the checkpoint, Border Patrol agents base their assessments of citizenship and enemyship on markers of race, language, class, and gender. To investigate the border checkpoint, I define rhetoric as a force that captures to account for the mechanisms at this site that lead to an imaginative, legal, and material capture. I examine the textual, physical, and metaphysical activity that animates and disrupts the checkpoint: Supreme Court cases, author-captured photographs, and archives of la Llorona subverting immigration enforcement
The Impacts of Virtual Learning on American and Taiwanese Medical Students' Learning Perceptions and Clinical Outcomes
No full textResearch Question: How did COVID-19-induced distance/virtual learning impact American and Taiwanese medical students¿ learning perceptions, engagement, and future willingness to participate in virtual learning opportunities compared to their experiences with traditional in-person learning?Background and Significance: The COVID-19 pandemic forced swift, unanticipated, and significant changes in every facet of daily life around the globe. Our personal social lives, work, education, daily chores, and perception of personal safety were turned on their head nearly overnight. As the world adapted to these changes, medical education was not spared. Coursework was moved online, and classrooms became isolated rooms connected via virtual conferencing software so that curricula could continue, and new generations of physicians could be trained. Though diligent effort was taken to maintain normalcy, the learning experience was undoubtedly altered compared to the traditional classroom style. However, amid these changes, little research has been done to try to quantify its effects on students. Essentially, we do not know how learners have perceived and been impacted by these changes, so we decided to try to quantify their opinions to better inform the medical education system moving forward.Materials and Methods: We created a robust survey and distributed it to two cohorts of medical students, one from Taiwan and one from the United States. It encompassed criteria such as prior experience with virtual learning, online learning engagement, perceived difficulty of online learning, and future interest/willingness to participate in online learning. Then, with their responses, we conducted an array of statistical analyses to better understand each cohort¿s opinions as well as how they agreed or disagreed with one another.Results: It was clear both cohorts had good familiarity with virtual learning, but the students in Taiwan appeared to be more adaptable and overall positive about their experiences. Intriguingly though, U.S. students reported stronger efforts in curriculum engagement and effort to succeed.Conclusion: Though some of the differences are undoubtedly linked to differences in culture between the two countries, we believe the prolonged use of online learning in the U.S. allowed those students to experience more of its challenges and therefore have a more negative overall opinion. In a free response section, both groups agreed online learning was beneficial for review of material and creating a more personalized learning experience, but also recognized the practice of medicine as a nuanced art and felt success in clinical mastery required face-to-face learning. Moving forward, we hope this research provides educators with insight into the student experience and aids in the creation of programming to help better support the needs of students engaged in primarily virtual learning environments