Structural Studies Of Sulfur Transfer In Thiocarboxylate-Dependent Methionine Biosynthesis

Macromolecular crystallography allows for the determination of structures to an atomic resolution and can provide important insight into the function and mechanism of enzymes. Including enzymes involved in interesting reactions and complex formations. In Wolinella succinogenes a sulfur carrier protein pathway was discovered to serve as the sulfur source for methionine biosynthesis. During this process, the sulfur carrier protein HcyS must form complexes with a variety of proteins to accomplish the C-terminal thiocarboxylate formation and the biosynthesis of methionine. This ability to form the different complex interactions makes the pathway fascinating in its structural characteristics. Additionally, the methionine pathway has a novel sulfur source when compared to other sulfur carrier protein pathways. The sulfur for the thiocarboxylate is supplied by ferredoxin sulfite reductase (FSR). The structure of FSR has been solved and reveals a more complex function than simply reducing sulfite to sulfide. The presence of a cysteine in the active site suggests the FSR may also serve as a sulfurtransferase to control the formation of the sulfur carrier protein thiocarboxylate. The structure of FSR provides further insight into the formation of complexes by HcyS

High-resolution multi-temporal analysis of geomorphic change on the Sandy Pond Spit, eastern shore of Lake Ontario, NY

Thesis advisor: Noah P. SnyderMulti-temporal elevation (MTE) analysis is used to study topographic changes at specific intervals. Barrier-island complexes are often studied using this MTE analysis to quantify changes to the environment after hurricanes to understand how dynamic landscapes respond to different forcings. The Sandy Pond spit (SPS) is a north-south trending barrier island on the eastern shore of Lake Ontario, New York, which responds dynamically to fluctuations in water levels, ice cover, and storms. Prior research reconstructed the geomorphic history of the SPS from 1878-2013, determining that the most significant factor affecting decadal change is the lake-water elevation. In the summers of 2017 and 2019, anomalously high precipitation and lake levels resulted in increased erosion along the SPS, and flooding in neighboring communities. In this study I used shoreline position, foredune crest position and elevation and volume of deposition and erosion to determine the dominant force of geometric change on the SPS before, during and after the high water events in 2017 and 2019, using the study period 2001-2020. Lidar data and small uncrewed aerial system images are used to generate digital elevation models (DEMs) and DEMs of difference (DoDs) from surveys conducted in May 2001, July 2007, June 2011, October 2015, May 2018, September 2018, July 2020 and August 2020. Results indicated water level was the most significant factor altering the topography of the SPS. Large storm events although erosive, were not as destructive to the shore environment as the long duration elevated summer water levels. From 2001-2015 the shoreline advanced an average of 0.25 m/year. From 2015-2018 and 2018-2020 the shoreline retreated 0.62 m/year, and 3.27 m/year respectively. The foredune position and elevation altered due to erosion of the dune toe caused by wave action and shoreline retreat from 2015-2020 compared to 2001-2015. To study volumetric changes, the SPS was split into seven ecogeomorphic zones that characterize the barrier-spit system at large. From 2007-2015 net deposition was recorded at five of the seven zones when applying a 95% confidence interval. The zones recording erosion were characterized by high dune complexes with sparse vegetation to anchor sand. From 2015-2018 net erosion was recorded in all seven zones, indicating water level had a statistically significant effect on the rate and volume of geomorphic change to this ecosystem.Thesis (MS) — Boston College, 2022.Submitted to: Boston College. Graduate School of Arts and Sciences.Discipline: Earth and Environmental Sciences

When Money Can’t Be Avoided: Helping Money Avoidant Widows Using the Changes and Grief Model (FTA Best Paper Award)

Widows represent one of the fastest-growing demographics due to the global COVID-19 pandemic. Many widows also lost their family’s financial manager because more men hold the role of household financial manager. When their spouse dies, the widow can experience unhealthy attitudes towards finances and financial anxiety. The Changes and Grief Model for Financial Guidance pairs financial therapy techniques and inquiry methods, such as The Work of Byron Katie®, with the grief process and the change cycle. Using this model enables financial practitioners, mental health practitioners, and financial therapists to recognize the stage of grief the widow is experiencing and use the proper financial therapy modalities to support the money-avoidant widow. The model presented will provide the process to deepen client relationships through meaningful communication while compassionately supporting money-avoidant widows through financial decisions during the difficult initial stages of grief

Structure and Molecular Mechanism of ER Stress Signaling by the Unfolded Protein Response Signal Activator IRE1

The endoplasmic reticulum (ER) is an important site for protein folding and maturation in eukaryotes. The cellular requirement to synthesize proteins within the ER is matched by its folding capacity. However, the physiological demands or aberrations in folding may result in an imbalance which can lead to the accumulation of misfolded protein, also known as “ER stress.” The unfolded protein response (UPR) is a cell-signaling system that readjusts ER folding capacity to restore protein homeostasis. The key UPR signal activator, IRE1, responds to stress by propagating the UPR signal from the ER to the cytosol. Here, we discuss the structural and molecular basis of IRE1 stress signaling, with particular focus on novel mechanistic advances. We draw a comparison between the recently proposed allosteric model for UPR induction and the role of Hsp70 during polypeptide import to the mitochondrial matrix

In vitro and in vivo functions of SARS-CoV-2 infection-enhancing and neutralizing antibodies

SARS-CoV-2 neutralizing antibodies (NAbs) protect against COVID-19. A concern regarding SARS-CoV-2 antibodies is whether they mediate disease enhancement. Here, we isolated NAbs against the receptor-binding domain (RBD) and the N-terminal domain (NTD) of SARS-CoV-2 spike from individuals with acute or convalescent SARS-CoV-2 or a history of SARS-CoV infection. Cryo-electron microscopy of RBD and NTD antibodies demonstrated function-specific modes of binding. Select RBD NAbs also demonstrated Fc receptor-g (FcgR)-mediated enhancement of virus infection in vitro, while five non-neutralizing NTD antibodies mediated FcgR-independent in vitro infection enhancement. However, both types of infection-enhancing antibodies protected from SARS-CoV-2 replication in monkeys and mice. Three of 46 monkeys infused with enhancing antibodies had higher lung inflammation scores compared to controls. One monkey had alveolar edema and elevated bronchoalveolar lavage inflammatory cytokines. Thus, while in vitro antibody-enhanced infection does not necessarily herald enhanced infection in vivo, increased lung inflammation can rarely occur in SARS-CoV-2 antibody-infused macaques

MalishEtAl2023_Ecosphere

Data: Files ending in _current of _future contain hydrological model output, used to caclulate continuity and connectivity metrics. File in map_stats folder contain continuity metric values. blue_fixed.rda and connectivity_wts.csv are used to calculate DCI. Code: ConnectivityMetrics.R contains code to calculate percent wet length, number of dry fragments, and average length of dry fragments. DCI.R contains code to calculate DCI. change_dryperiodlength.R, change_dryperiods.R, and change_zeroflowdays.R contain code to calculate change in continuity metrics.</p

Structural and Biochemical Characterization of 6-Hydroxynicotinic Acid 3-Monooxygenase, A Novel Decarboxylative Hydroxylase Involved in Aerobic Nicotinate Degradation

The genes coding for the enzymes of oxidative degradation of nicotinic acid have recently been identified in several species of aerobic bacteria, namely, Pseudomonas putida KT2440, Bordetella bronchiseptica RB50, and Bacillus niacini. One of the enzymes involved in an early step of this pathway is a flavin-dependent monooxygenase (6-hydroxynicotinic acid 3-monooxygenase; NicC) that catalyzes the decarboxylative hydroxylation of 6-hydroxynicotinic acid (6-HNA) to 2,5-dihydroxypyridine (2,5-DHP), with concomitant oxidation of NADH to NAD+. The nicC genes from B. bronchiseptica RB50 and P. putida have been cloned, and the purified enzymes have been characterized functionally and structurally. Global fits of the steady-state kinetic data show that both enzymes are efficient catalysts, with an apparent kcat/KM6-HNA of 5.0 × 104 M–1 s–1 for B. bronchiseptica NicC. The pH dependence of Vmax/[E]t fits a double-bell model showing an optimum around pH 8 with apparent pKas of 7.24 ± 0.08 and 8.64 ± 0.08, whereas the apparent catalytic efficiency (kcat/KM6-HNA) is maximal around pH 7 and decreases at high pH with an apparent pKa of 7.60 ± 0.06. The enzyme’s relative affinity for 6-hydroxynicotinaldehyde, a neutral analogue that shows competitive inhibition with respect to 6-HNA, is weak (Ki = 3000 ± 400 μM) in comparison to the apparent binding of 6-HNA (KM = 85 ± 13 μM). The crystal structure for P. putida NicC has been solved to 2.1 Å using SAD phasing, and the 6-HNA substrate has been modeled into the active site. Together these data provide insight into potential reaction mechanisms for this novel decarboxylative hydroxylation reaction

Occupational Therapists in Disaster Management: A Survey Study

Purpose: There is a need for occupational therapy involvement in disaster management from preparation to response. To understand why OTs are not involved with disaster management, this study explored perceived disaster management roles for healthcare professionals; the level of familiarity and professional experience with stages of disaster; and the relationship between training and likelihood of engagement. Method: The Healthcare Practitioner Disaster Management Questionnaire, an anonymous quantitative survey, was deployed to licensed OTs and OT assistants (OTAs) practicing in 14 states in the US (a convenience sample). Descriptive analysis and Spearman Rho correlation were used to understand the data. Results: OTs and OTAs believe that clinicians have a role in disaster management and identified nurses, physician assistants, and occupational therapists as having useful skills. Respondents had little familiarity, little professional experience, and little to no training in disaster management stages. Spearman correlation revealed a small positive correlation between training and the likelihood of responding to a disaster. Conclusions: Occupational therapists perceive healthcare professionals to have roles in disaster management; however, there is a lack of training and involvement. A positive correlation between training and the likelihood of responding suggests that as therapists receive training, the likelihood of engagement increases. Hopefully, this information will increase awareness of the need for involvement in disaster management to address the health and welfare of people and communities. Educators and continuing education providers need to train occupational therapists (OTs) from entry-level to practicing therapists to address the needs of populations affected by disasters