Publications by authors named "John Peters"

399 Publications

Hard Nodular Plaque on the Scalp.

Cutis 2021 Jun;107(6):E12-E14

Dr. Gall is from the National Capital Consortium, Bethesda, Maryland. Drs. Brinker and Peters are from the Dermatology Department, Naval Medical Center San Diego, California.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.12788/cutis.0283DOI Listing
June 2021

The unique Phe-His dyad of 2-ketopropyl coenzyme M oxidoreductase/carboxylase selectively promotes carboxylation and S-C bond cleavage.

J Biol Chem 2021 Jul 12:100961. Epub 2021 Jul 12.

Institute of Biological Chemistry, Washington State University, Pullman, WA, 99163. Electronic address:

The 2-ketopropyl coenzyme M oxidoreductase/carboxylase (2-KPCC) enzyme is the only member of the disulfide oxidoreductase (DSOR) family of enzymes, which are important for reductively cleaving S-S bonds, to have carboxylation activity. 2-KPCC catalyzes the conversion of 2-ketopropyl coenzyme M (2-KPC) to acetoacetate, which is used as a carbon source, in a controlled reaction to exclude protons. A conserved His-Glu motif present in DSORs is key in the protonation step; however, in 2-KPCC the dyad is substituted by Phe-His. Here we propose this difference is important for coupling carboxylation with C-S bond cleavage. We substituted the Phe-His dyad in 2-KPCC to be more DSOR-like, replacing the phenylalanine with histidine (F501H) and the histidine with glutamate (H506E), and solved crystal structures of F501H and the double variant F501H_H506E. We found that F501 protects the enolacetone intermediate from protons and that the F501H variant strongly promotes protonation. We also provided evidence for the involvement of the H506 residue in stabilizing the developing charge during the formation of acetoacetate, which acts as a product inhibitor in the WT but not the H506E variant enzymes. Finally, utilizing a variety of methods to inhibit the catalytic cysteines shared among all DSORs, we determined that the F501H substitution promotes a DSOR-like charge transfer interaction with FAD, eliminating the need for cysteine as an internal base. Taken together, these results indicate that the 2-KPCC dyad is responsible for selectively promoting carboxylation and inhibiting protonation in the formation of acetoacetate.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jbc.2021.100961DOI Listing
July 2021

HydG, the "dangler" iron, and catalytic production of free CO and CN: implications for [FeFe]-hydrogenase maturation.

Dalton Trans 2021 Jul 9. Epub 2021 Jul 9.

Department of Chemistry & Biochemistry, Montana State University, Bozeman, MT 59717, USA.

The organometallic H-cluster of the [FeFe]-hydrogenase consists of a [4Fe-4S] cubane bridged via a cysteinyl thiolate to a 2Fe subcluster ([2Fe]H) containing CO, CN-, and dithiomethylamine (DTMA) ligands. The H-cluster is synthesized by three dedicated maturation proteins: the radical SAM enzymes HydE and HydG synthesize the non-protein ligands, while the GTPase HydF serves as a scaffold for assembly of [2Fe]H prior to its delivery to the [FeFe]-hydrogenase containing the [4Fe-4S] cubane. HydG uses l-tyrosine as a substrate, cleaving it to produce p-cresol as well as the CO and CN- ligands to the H-cluster, although there is some question as to whether these are formed as free diatomics or as part of a [Fe(CO)2(CN)] synthon. Here we show that Clostridium acetobutylicum (C.a.) HydG catalyzes formation of multiple equivalents of free CO at rates comparable to those for CN- formation. Free CN- is also formed in excess molar equivalents over protein. A g = 8.9 EPR signal is observed for C.a. HydG reconstituted to load the 5th "dangler" iron of the auxiliary [4Fe-4S][FeCys] cluster and is assigned to this "dangler-loaded" cluster state. Free CO and CN- formation and the degree of activation of [FeFe]-hydrogenase all occur regardless of dangler loading, but are increased 10-35% in the dangler-loaded HydG; this indicates the dangler iron is not essential to this process but may affect relevant catalysis. During HydG turnover in the presence of myoglobin, the g = 8.9 signal remains unchanged, indicating that a [Fe(CO)2(CN)(Cys)] synthon is not formed at the dangler iron. Mutation of the only protein ligand to the dangler iron, H272, to alanine nearly completely abolishes both free CO formation and hydrogenase activation, however results show this is not due solely to the loss of the dangler iron. In experiments with wild type and H272A HydG, and with different degrees of dangler loading, we observe a consistent correlation between free CO/CN- formation and hydrogenase activation. Taken in full, our results point to free CO/CN-, but not an [Fe(CO)2(CN)(Cys)] synthon, as essential species in hydrogenase maturation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1039/d1dt01359aDOI Listing
July 2021

Mechanical coupling in the nitrogenase complex.

PLoS Comput Biol 2021 03 4;17(3):e1008719. Epub 2021 Mar 4.

Physical and Computational Sciences Directorate, Pacific Northwestern National Laboratory, Richland, Washington United States of America.

The enzyme nitrogenase reduces dinitrogen to ammonia utilizing electrons, protons, and energy obtained from the hydrolysis of ATP. Mo-dependent nitrogenase is a symmetric dimer, with each half comprising an ATP-dependent reductase, termed the Fe Protein, and a catalytic protein, known as the MoFe protein, which hosts the electron transfer P-cluster and the active-site metal cofactor (FeMo-co). A series of synchronized events for the electron transfer have been characterized experimentally, in which electron delivery is coupled to nucleotide hydrolysis and regulated by an intricate allosteric network. We report a graph theory analysis of the mechanical coupling in the nitrogenase complex as a key step to understanding the dynamics of allosteric regulation of nitrogen reduction. This analysis shows that regions near the active sites undergo large-scale, large-amplitude correlated motions that enable communications within each half and between the two halves of the complex. Computational predictions of mechanically regions were validated against an analysis of the solution phase dynamics of the nitrogenase complex via hydrogen-deuterium exchange. These regions include the P-loops and the switch regions in the Fe proteins, the loop containing the residue β-188Ser adjacent to the P-cluster in the MoFe protein, and the residues near the protein-protein interface. In particular, it is found that: (i) within each Fe protein, the switch regions I and II are coupled to the [4Fe-4S] cluster; (ii) within each half of the complex, the switch regions I and II are coupled to the loop containing β-188Ser; (iii) between the two halves of the complex, the regions near the nucleotide binding pockets of the two Fe proteins (in particular the P-loops, located over 130 Å apart) are also mechanically coupled. Notably, we found that residues next to the P-cluster (in particular the loop containing β-188Ser) are important for communication between the two halves.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1371/journal.pcbi.1008719DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7963043PMC
March 2021

MOG-associated encephalitis following SARS-COV-2 infection.

Mult Scler Relat Disord 2021 May 23;50:102857. Epub 2021 Feb 23.

Department of Neurology, Yale University School of Medicine, 333 Cedar St. New Haven, CT, 06510, USA.

A variety of neurologic manifestations of COVID-19 infections have been reported. Here, we present a case of steroid-responsive MOG-antibody associated encephalitis, characterized by cognitive decline, headaches, fever, unilateral FLAIR-hyperintensities, and leptomeningeal enhancement, that occurred in the setting of recent COVID-19 infection.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.msard.2021.102857DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7900751PMC
May 2021

Predictors of attendance during an exercise program for cancer survivors.

Support Care Cancer 2021 Jul 16;29(7):3425-3428. Epub 2021 Feb 16.

University of Colorado Cancer Center, Aurora, USA.

Purpose: Exercise programs delivered in community- or clinic-based settings improve physical and psychosocial outcomes among cancer survivors; however, adherence is essential to achieve such benefits. This study examined predictors of attendance to an exercise program in a large, diverse sample of cancer survivors.

Methods: Participants (n = 302) were enrolled in BfitBwell, an exercise program for adults diagnosed with cancer, and currently receiving or within 6 months of completing chemotherapy or radiation therapy. Participants were offered two supervised aerobic and resistance exercise sessions per week for 3 months. Predictors of attendance included demographics, cancer-related information, quality of life (QOL), fatigue, physical fitness, activity level, and importance of making various changes (e.g., improving fitness). Univariate linear regression first explored associations between predictor variables and adherence, and any important variables (p < .10) were included in a multivariate linear regression model.

Results: Participants were M = 54.9 ± 13.9 years old, mostly female (67.3%), white (83.6%), and most commonly diagnosed with breast cancer (34.8%). Average attendance was 16.2 ± 6.6 exercise sessions. Six-minute walk test distance, QOL, and fatigue were associated with exercise session attendance (p < .05). The multivariable model revealed that higher QOL predicted higher attendance (β = .351, p = .005), and working full- or part-time significantly predicted lower attendance (β =- .221, p =.021).

Conclusions: Higher pre-program QOL and not working full- or part-time predicted higher exercise program attendance. Existing and future exercise programs for cancer survivors should consider ways to adapt program delivery to provide support to survivors who start with low QOL, and accommodate those who may face barriers to attending due to work schedule/conflict.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00520-021-06057-4DOI Listing
July 2021

Comment on "Structural evidence for a dynamic metallocofactor during N reduction by Mo-nitrogenase".

Science 2021 02;371(6530)

Chemistry and Biochemistry, Utah State University, Logan, UT 84322, USA.

Kang (Reports, 19 June 2020, p. 1381) report a structure of the nitrogenase MoFe protein that is interpreted to indicate binding of N or an N-derived species to the active-site FeMo cofactor. Independent refinement of the structure and consideration of biochemical evidence do not support this claim.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1126/science.abe5481DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7931246PMC
February 2021

Catalytic bias in oxidation-reduction catalysis.

Chem Commun (Camb) 2021 Jan 24;57(6):713-720. Epub 2020 Dec 24.

Biosciences Center, National Renewable Energy Laboratory, Golden, CO 80401, USA.

Cataytic bias refers to the propensity of a reaction catalyst to effect a different rate acceleration in one direction versus the other in a chemical reaction under non-equilibrium conditions. In biocatalysis, the inherent bias of an enzyme is often advantagous to augment the innate thermodynamics of a reaction to promote efficiency and fidelity in the coordination of catabolic and anabolic pathways. In industrial chemical catalysis a directional cataltyic bias is a sought after property in facilitating the engineering of systems that couple catalysis with harvest and storage of for example fine chemicals or energy compounds. Interestingly, there is little information about catalytic bias in biocatalysis likely in large part due to difficulties in developing tractible assays sensitive enough to study detailed kinetics. For oxidation-reduction reactions, colorimetric redox indicators exist in a range of reduction potentials to provide a mechanism to study both directions of reactions in a fairly facile manner. The current short review attempts to define catalytic bias conceptually and to develop model systems for defining the parameters that control catalytic bias in enzyme catalyzed oxidation-reduction catalysis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1039/d0cc07062aDOI Listing
January 2021

Effects of a Clinic-Based Exercise Program on Sleep Disturbance Among Cancer Survivors.

Integr Cancer Ther 2020 Jan-Dec;19:1534735420975852

School of Medicine, University of Colorado, Aurora, CO, USA.

Introduction: Sleep disturbance is the second leading negative side effect reported by cancer survivors, and evidence exists to suggest that exercise may improve sleep for cancer survivors. This study examined changes in sleep following a 3-month, clinic-based exercise program among a diverse group of cancer survivors.

Methods: Single group, pre-post study design. Participants were enrolled in a supervised exercise program which consisted of moderate intensity aerobic and resistance training, twice per week for 3-months. To be eligible, individuals had to be diagnosed with cancer, and undergoing, or within 6-months of completing chemo and/or radiation therapy. Sleep was assessed at pre-and post-program using 3 self-report questions as part of a standard wellness assessment conducted at the program's facility. Changes in categorical outcomes were evaluated using McNemar and Wilcoxon Signed-Rank Tests.

Results: Participants ( = 94) were mostly female (68.1%, = 64), mean age = 54.26 ± 14.26 (20-78), and diagnosed with more than 8 different cancer types. Half ( = 48, 51.1%) of participants improved on 1 or more of the questions assessing sleep. At post-program, 39% of participants reported that they did not awaken feeling rested versus 48% at pre-program ( = .08). At post-program, 47% reported awakening ≥1 time per night versus 46% at pre-program ( = .97), and 17% reported poor or very poor sleep quality at post-program versus 24% at pre-program ( = .16). There were no differences in demographic, cancer-related, psychosocial, and physical fitness variables between participants who improved on any of the questions assessing sleep versus those who did not.

Conclusions: A clinically implemented exercise program may help some cancer survivors improve sleep, however more studies utilizing validated, objective measures of sleep are needed to confirm effectiveness.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/1534735420975852DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7705805PMC
November 2020

Erythematous abdominal nodule.

Cutis 2020 Oct;106(4):E2-E3

Naval Medical Center San Diego, California, USA.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.12788/cutis.0096DOI Listing
October 2020

Experimentally Manipulated Low Social Status and Food Insecurity Alter Eating Behavior Among Adolescents: A Randomized Controlled Trial.

Obesity (Silver Spring) 2020 11;28(11):2010-2019

Department of Epidemiology and Biostatistics, School of Public Health, Indiana University-Bloomington, Bloomington, Indiana, USA.

Objective: This randomized trial experimentally manipulated social status to assess effects on acute eating behavior and 24-hour energy balance.

Methods: Participants (n = 133 Hispanics; age 15-21 years; 60.2% females) were randomized to low social status ("LOW") or high social status ("HIGH") conditions in a rigged game of Monopoly (Hasbro, Inc.). Acute energy intake in a lunchtime meal was measured by food scales. Twenty-four-hour energy balance was assessed via summation of resting metabolic rate (metabolic cart), physical activity energy expenditure (accelerometer), thermic effect of food, and subtraction of twenty-four-hour energy intake (food diary).

Results: In the total sample, no significant differences were observed by study condition at lunchtime. LOW females consumed a greater percent of lunchtime daily energy needs (37.5%) relative to HIGH females (34.3%); however, this difference was not statistically significant (P = 0.291). In males, however, LOW consumed significantly less (36.5%) of their daily energy needs relative to HIGH males (45.8%; P = 0.001). For 24-hour energy balance, sex differences were nearly significant (P = 0.057; LOW females: surplus +200 kcal; HIGH males: surplus +445 kcal). Food-insecure individuals consumed a nearly significant greater lunchtime percent daily energy than those with food security (40.7% vs. 36.3%; P = 0.0797).

Conclusions: The data demonstrate differential acute and 24-hour eating behavior responses between Hispanic male and female adolescents in experimentally manipulated conditions of low social status.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/oby.23002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7653825PMC
November 2020

Revealing a role for the G subunit in mediating interactions between the nitrogenase component proteins.

J Inorg Biochem 2021 Jan 7;214:111273. Epub 2020 Oct 7.

Institute of Biological Chemistry, Washington State University, Pullman, WA 99164, United States of America. Electronic address:

Azotobacter vinelandii contains three forms of nitrogenase known as the Mo-, V-, and Fe-nitrogenases. They are all two-component enzyme systems, where the catalytic component, referred to as NifDK, VnfDGK, and AnfDGK, associates with the reductase component, the Fe protein or NifH, VnfH, and AnfH respectively. AnfDGK and VnfDGK have an additional subunit compared to NifDK, termed gamma or AnfG and VnfG, whose role is unknown. The expression of each nitrogenase is tightly regulated by metal availability, however it is known that there is crosstalk between the Mo- and V‑nitrogenases but the Fe‑nitrogenase components cannot support substrate reduction with its Mo‑nitrogenase counterparts. Here, docking models for the nitrogenase complexes were generated in ClusPro 2.0 based on the crystal structure of the Mo‑nitrogenase and refined using the HADDOCK 2.2 refinement interface to identify structural determinants that enable crosstalk between the Mo- and V‑nitrogenase but not the Fe‑nitrogenase. Differing salt bridge interactions were identified at the binding interface of each complex. Specifically, positively charged residues of VnfG enable complementary interactions with NifH and VnfH but not AnfH. Similarly, negatively charged residues of AnfG enable interactions with AnfH but not NifH or VnfH. A role for the G subunit is revealed where VnfG could be mediating crosstalk between the Mo- and V‑nitrogenases while the AnfG subunit on AnfDGK makes interactions with NifH and VnfH unfavorable, reducing competition with NifDK and funneling electrons to the most efficient nitrogenase.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jinorgbio.2020.111273DOI Listing
January 2021

Case of concurrent herpes simplex and autoimmune encephalitis.

Neurol Neuroimmunol Neuroinflamm 2020 11 2;7(6). Epub 2020 Oct 2.

From the Department of Neurology, Yale University School of Medicine.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1212/NXI.0000000000000897DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7577525PMC
November 2020

Defining Intermediates of Nitrogenase MoFe Protein during N Reduction under Photochemical Electron Delivery from CdS Quantum Dots.

J Am Chem Soc 2020 08 5;142(33):14324-14330. Epub 2020 Aug 5.

Biosciences Center, National Renewable Energy Laboratory, Golden, Colorado 80401, United States.

Coupling the nitrogenase MoFe protein to light-harvesting semiconductor nanomaterials replaces the natural electron transfer complex of Fe protein and ATP and provides low-potential photoexcited electrons for photocatalytic N reduction. A central question is how direct photochemical electron delivery from nanocrystals to MoFe protein is able to support the multielectron ammonia production reaction. In this study, low photon flux conditions were used to identify the initial reaction intermediates of CdS quantum dot (QD):MoFe protein nitrogenase complexes under photochemical activation using EPR. Illumination of CdS QD:MoFe protein complexes led to redox changes in the MoFe protein active site FeMo-co observed as the gradual decline in the E resting state intensity that was accompanied by an increase in the intensity of a new " = 4.5" EPR signal. The magnetic properties of the = 4.5 signal support assignment as a reduced = 3/2 state, and reaction modeling was used to define it as a two-electron-reduced "E" intermediate. Use of a MoFe protein variant, β-188, which poises the P cluster in the oxidized P state, demonstrated that the P cluster can function as a site of photoexcited electron delivery from CdS to MoFe protein. Overall, the results establish the initial steps for how photoexcited CdS delivers electrons into the MoFe protein during reduction of N to ammonia and the role of electron flux in the photochemical reaction cycle.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/jacs.0c06343DOI Listing
August 2020

Making connections: nationwide implementation of video telehealth tablets to address access barriers in veterans.

JAMIA Open 2019 Oct 5;2(3):323-329. Epub 2019 Aug 5.

Office of Connected Care/Telehealth Services, Veterans Health Administration.

Background: Video telehealth technology has the potential to enhance access for patients with clinical, social, and geographic barriers to care. We evaluated the implementation of a US Department of Veterans Affairs (VA) initiative to distribute tablets to high-need Veterans with access barriers.

Methods: In this mixed methods implementation study, we examined tablet adoption (ie, facility-level tablet distribution rates and patient-level tablet utilization rates) and reach (ie, sociodemographic and clinical characteristics of tablet recipients) between 5/1/16 and 9/30/17. Concurrently, we surveyed 68 facility telehealth coordinators to determine the most common implementation barriers and facilitators, and then conducted interviews with telehealth coordinators and regional leadership to identify strategies that facilitated tablet distribution and use.

Results: 86 VA facilities spanning all 18 geographic regions, distributed tablets to 6 745 patients. Recipients had an average age of 56 years, 53% lived in rural areas, 75% had a diagnosed mental illness, and they had a mean (SD) of 5 (3) chronic conditions. Approximately 4 in 5 tablet recipients used the tablet during the evaluation period. In multivariate logistic regression, tablet recipients were more likely to use their tablets if they were older and had fewer chronic conditions. Implementation barriers included insufficient training, staffing shortages, and provider disinterest (described as barriers by 59%, 55%, and 33% of respondents, respectively). Site readiness assessments, local champions, licensure modifications, and use of mandates and incentives were identified as strategies that may influence widespread implementation of home-based video telehealth.

Conclusion: VA's initiative to distribute video telehealth tablets to high-need patients appears to have successfully reached individuals with social and clinical access barriers. Implementation strategies that address staffing constraints and provider engagement may enhance the impact of such efforts.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/jamiaopen/ooz024DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6952023PMC
October 2019

Neuropathy Mimicking Dental Pain in a Patient Diagnosed with Lyme Disease.

J Endod 2020 Sep 17;46(9):1337-1339. Epub 2020 Jun 17.

Department of Dental Clinical Sciences, Faculty of Dentistry, Dalhousie University, Halifax, NS, Canada.

This report documents the case of a patient who developed neuropathy that presented as dental pain and was later diagnosed with Lyme disease. A healthy female patient presented to the endodontist with toothache symptoms. Her symptoms included intense pain in the left mandible irradiating into the temporalis area and through her neck and tingling on the lower left lip and left side of her tongue. She also reported feeling of sweats and chills the night before, as well as an altered sensation in her shoulder and arm. The pain was not alleviated by over-the-counter analgesics. Both intraoral and radiographic examinations did not reveal any abnormalities, and the patient was presented with the following differential diagnoses: cardiac issues, trigeminal neuralgia, and temporomandibular dysfunction. She presented to the emergency department at the local hospital for assessment on the same day. After some tests were performed, both a stroke and myocardial infarction were ruled out. The following morning, she noticed a bump in the posterior area of her left upper thigh where an erythema with a bull's-eye appearance was observed. She presented to her family doctor's office on the same day and was diagnosed with Lyme disease. Because Lyme disease can present with symptoms similar to a toothache, dentists should be knowledgeable of its manifestations. Lyme disease should be considered as differential diagnosis in patients who present with compatible symptoms and signs, which may occur in the orofacial region.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.joen.2020.06.011DOI Listing
September 2020

Insights into the unique carboxylation reactions in the metabolism of propylene and acetone.

Biochem J 2020 06;477(11):2027-2038

Institute of Biological Chemistry, Washington State University, Pullman, WA 99164, U.S.A.

Alkenes and ketones are two classes of ubiquitous, toxic organic compounds in natural environments produced in several biological and anthropogenic processes. In spite of their toxicity, these compounds are utilized as primary carbon and energy sources or are generated as intermediate metabolites in the metabolism of other compounds by many diverse bacteria. The aerobic metabolism of some of the smallest and most volatile of these compounds (propylene, acetone, isopropanol) involves novel carboxylation reactions resulting in a common product acetoacetate. Propylene is metabolized in a four-step pathway involving five enzymes where the penultimate step is a carboxylation reaction catalyzed by a unique disulfide oxidoreductase that couples reductive cleavage of a thioether linkage with carboxylation to produce acetoacetate. The carboxylation of isopropanol begins with conversion to acetone via an alcohol dehydrogenase. Acetone is converted to acetoacetate in a single step by an acetone carboxylase which couples the hydrolysis of MgATP to the activation of both acetone and bicarbonate, generating highly reactive intermediates that are condensed into acetoacetate at a Mn2+ containing the active site. Acetoacetate is then utilized in central metabolism where it is readily converted to acetyl-coenzyme A and subsequently converted into biomass or utilized in energy metabolism via the tricarboxylic acid cycle. This review summarizes recent structural and biochemical findings that have contributed significant insights into the mechanism of these two unique carboxylating enzymes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1042/BCJ20200174DOI Listing
June 2020

Reno-duodenal fistula as a complication of longstanding renal tract calculus.

Oxf Med Case Reports 2019 Dec 31;2019(12):498-501. Epub 2019 Dec 31.

Department of Urology, Whipps Cross University Hospital, Barts Health NHS Trust, Whipps Cross Road, Leytonstone, London E11 1NR, UK.

We present a rare case detailing the investigations and subsequent treatment of a lady who presented with a reno-duodenal fistula and perinephric abscess as a complication of staghorn calculus and recurrent upper urinary tract infections. Treatment involved antibiotics, nephrostomy, endoscopic closure of the fistula tract with clips, radiological drain insertion and, ultimately, nephrectomy with primary omental patch closure of the duodenal defect. We discuss the incidence of fistula tract formation as a complication of staghorn calculi, as well as investigations and management strategies employed in the literature to treat such complications, which span from conservative treatment to nephrectomy and closure of the intestinal defect. We illustrate the post-operative complications such patients are prone to and discuss these in context of the case. Whilst such cases are rare clinicians should be vigilant for complications associated with chronic inflammatory processes occurring in the urinary tract and investigate accordingly.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/omcr/omz083DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6937454PMC
December 2019

Performance profiling as an intelligence-led approach to antidoping in sports.

Drug Test Anal 2020 Mar 21;12(3):402-409. Epub 2020 Jan 21.

KIHU - Research Institute for Olympic Sports, Jyvaskyla, Finland.

The efficient use of testing resources is crucial in the fight against doping in sports. The athlete biological passport relies on the need to identify the right athletes to test, and the right time to test them. Here we present an approach to longitudinal tracking of athlete performance to provide an additional, more intelligence-led approach to improve targeted antidoping testing. The performance results of athletes (male shot putters, male 100 m sprinters, and female 800 m runners) were obtained from a performance results database. Standardized performances, which adjust for average career performance, were calculated to determine the volatility in performance over an athlete's career. We then used a Bayesian spline model to statistically analyse changes within an athlete's standardized performance over the course of a career both for athletes who were presumed "clean" (not doped), and those previously convicted of doping offences. We used the model to investigate changes in the slope of each athlete's career performance trajectory and whether these changes can be linked to doping status. The model was able to identify differences in the standardized performance of clean and doped athletes, with the sign of the change able to provide some discrimination. Consistent patterns of standardized performance profile are seen across shot put, 100 m and 800 m for both the clean and doped athletes we investigated. This study demonstrates the potential for modeling athlete performance data to distinguish between the career trajectories of clean and doped athletes, and to enable the risk stratification of athletes on their risk of doping.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/dta.2748DOI Listing
March 2020

Control of nitrogen fixation in bacteria that associate with cereals.

Nat Microbiol 2020 02 16;5(2):314-330. Epub 2019 Dec 16.

Synthetic Biology Center, Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA.

Legumes obtain nitrogen from air through rhizobia residing in root nodules. Some species of rhizobia can colonize cereals but do not fix nitrogen on them. Disabling native regulation can turn on nitrogenase expression, even in the presence of nitrogenous fertilizer and low oxygen, but continuous nitrogenase production confers an energy burden. Here, we engineer inducible nitrogenase activity in two cereal endophytes (Azorhizobium caulinodans ORS571 and Rhizobium sp. IRBG74) and the well-characterized plant epiphyte Pseudomonas protegens Pf-5, a maize seed inoculant. For each organism, different strategies were taken to eliminate ammonium repression and place nitrogenase expression under the control of agriculturally relevant signals, including root exudates, biocontrol agents and phytohormones. We demonstrate that R. sp. IRBG74 can be engineered to result in nitrogenase activity under free-living conditions by transferring a nif cluster from either Rhodobacter sphaeroides or Klebsiella oxytoca. For P. protegens Pf-5, the transfer of an inducible cluster from Pseudomonas stutzeri and Azotobacter vinelandii yields ammonium tolerance and higher oxygen tolerance of nitrogenase activity than that from K. oxytoca. Collectively, the data from the transfer of 12 nif gene clusters between 15 diverse species (including Escherichia coli and 12 rhizobia) help identify the barriers that must be overcome to engineer a bacterium to deliver a high nitrogen flux to a cereal crop.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41564-019-0631-2DOI Listing
February 2020

MicroCT vascular network analysis program: Development, validation, and comparison to manufacturer software.

J Orthop Res 2020 06 19;38(6):1340-1350. Epub 2019 Dec 19.

Department of Orthopaedic Surgery, Saint Louis University, St Louis, Missouri.

The dependence on angiogenesis for bone repair makes accurate measuring of vascular networks of great importance to orthopedic researchers. A three-dimensional imaging modality like microcomputed tomography (µCT) would better capture these networks than histology. There are commercially available programs to analyze vessel networks in three dimensions, but these may be too costly for laboratories. Alternatively, µCT trabecular software could be used but may not be appropriate. The goal of this project was to develop a vascular network analysis protocol based on freely or commonly available software and compare its performance to that of a µCT trabecular analysis software. The protocol developed, called vascular network analysis or VNA, relies on two modules in Fiji ImageJ and a custom MATLAB program. We validated the software and compared it to a µCT trabecular analysis program (MicroCT) using in silico models of increasing complexity and differing homogeneity. In general, VNA outcomes were significantly different from true values, but most were within an acceptable percent error (<10%). VNA and MicroCT performed almost identically for volume but significantly differently for average vessel diameter. For the homogenous models, the average diameters differed only slightly but were starkly different for the heterogeneous models. In the most heterogeneous system, the MicroCT software overestimated average diameter by about 650% from true. VNA was within 1% of true for the same model. In conclusion, we have developed a program to analyze vascular networks from MicroCT scans which is easily accessible, insensitive to network homogeneity, and of higher accuracy compared to a µCT trabecular analysis software.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jor.24568DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7790441PMC
June 2020

Tuning Catalytic Bias of Hydrogen Gas Producing Hydrogenases.

J Am Chem Soc 2020 01 10;142(3):1227-1235. Epub 2020 Jan 10.

Institute of Biological Chemistry , Washington State University , Pullman , Washington 99164 , United States.

Hydrogenases display a wide range of catalytic rates and biases in reversible hydrogen gas oxidation catalysis. The interactions of the iron-sulfur-containing catalytic site with the local protein environment are thought to contribute to differences in catalytic reactivity, but this has not been demonstrated. The microbe produces three [FeFe]-hydrogenases that differ in "catalytic bias" by exerting a disproportionate rate acceleration in one direction or the other that spans a remarkable 6 orders of magnitude. The combination of high-resolution structural work, biochemical analyses, and computational modeling indicates that protein secondary interactions directly influence the relative stabilization/destabilization of different oxidation states of the active site metal cluster. This selective stabilization or destabilization of oxidation states can preferentially promote hydrogen oxidation or proton reduction and represents a simple yet elegant model by which a protein catalytic site can confer catalytic bias.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/jacs.9b08756DOI Listing
January 2020

THE CONCISE GUIDE TO PHARMACOLOGY 2019/20: Introduction and Other Protein Targets.

Br J Pharmacol 2019 12;176 Suppl 1:S1-S20

Centre for Discovery Brain Sciences, University of Edinburgh, Edinburgh, EH8 9XD, UK.

The Concise Guide to PHARMACOLOGY 2019/20 is the fourth in this series of biennial publications. The Concise Guide provides concise overviews of the key properties of nearly 1800 human drug targets with an emphasis on selective pharmacology (where available), plus links to the open access knowledgebase source of drug targets and their ligands (www.guidetopharmacology.org), which provides more detailed views of target and ligand properties. Although the Concise Guide represents approximately 400 pages, the material presented is substantially reduced compared to information and links presented on the website. It provides a permanent, citable, point-in-time record that will survive database updates. The full contents of this section can be found at http://onlinelibrary.wiley.com/doi/10.1111/bph.14747. In addition to this overview, in which are identified Other protein targets which fall outside of the subsequent categorisation, there are six areas of focus: G protein-coupled receptors, ion channels, nuclear hormone receptors, catalytic receptors, enzymes and transporters. These are presented with nomenclature guidance and summary information on the best available pharmacological tools, alongside key references and suggestions for further reading. The landscape format of the Concise Guide is designed to facilitate comparison of related targets from material contemporary to mid-2019, and supersedes data presented in the 2017/18, 2015/16 and 2013/14 Concise Guides and previous Guides to Receptors and Channels. It is produced in close conjunction with the International Union of Basic and Clinical Pharmacology Committee on Receptor Nomenclature and Drug Classification (NC-IUPHAR), therefore, providing official IUPHAR classification and nomenclature for human drug targets, where appropriate.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/bph.14747DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6844537PMC
December 2019

THE CONCISE GUIDE TO PHARMACOLOGY 2019/20: Nuclear hormone receptors.

Br J Pharmacol 2019 12;176 Suppl 1:S229-S246

Centre for Discovery Brain Sciences, University of Edinburgh, Edinburgh, EH8 9XD, UK.

The Concise Guide to PHARMACOLOGY 2019/20 is the fourth in this series of biennial publications. The Concise Guide provides concise overviews of the key properties of nearly 1800 human drug targets with an emphasis on selective pharmacology (where available), plus links to the open access knowledgebase source of drug targets and their ligands (www.guidetopharmacology.org), which provides more detailed views of target and ligand properties. Although the Concise Guide represents approximately 400 pages, the material presented is substantially reduced compared to information and links presented on the website. It provides a permanent, citable, point-in-time record that will survive database updates. The full contents of this section can be found at http://onlinelibrary.wiley.com/doi/10.1111/bph.14750. Nuclear hormone receptors are one of the six major pharmacological targets into which the Guide is divided, with the others being: G protein-coupled receptors, catalytic receptors, enzymes and transporters. These are presented with nomenclature guidance and summary information on the best available pharmacological tools, alongside key references and suggestions for further reading. The landscape format of the Concise Guide is designed to facilitate comparison of related targets from material contemporary to mid-2019, and supersedes data presented in the 2017/18, 2015/16 and 2013/14 Concise Guides and previous Guides to Receptors and Channels. It is produced in close conjunction with the International Union of Basic and Clinical Pharmacology Committee on Receptor Nomenclature and Drug Classification (NC-IUPHAR), therefore, providing official IUPHAR classification and nomenclature for human drug targets, where appropriate.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/bph.14750DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6844575PMC
December 2019

THE CONCISE GUIDE TO PHARMACOLOGY 2019/20: G protein-coupled receptors.

Br J Pharmacol 2019 12;176 Suppl 1:S21-S141

Centre for Discovery Brain Sciences, University of Edinburgh, Edinburgh, EH8 9XD, UK.

The Concise Guide to PHARMACOLOGY 2019/20 is the fourth in this series of biennial publications. The Concise Guide provides concise overviews of the key properties of nearly 1800 human drug targets with an emphasis on selective pharmacology (where available), plus links to the open access knowledgebase source of drug targets and their ligands (www.guidetopharmacology.org), which provides more detailed views of target and ligand properties. Although the Concise Guide represents approximately 400 pages, the material presented is substantially reduced compared to information and links presented on the website. It provides a permanent, citable, point-in-time record that will survive database updates. The full contents of this section can be found at http://onlinelibrary.wiley.com/doi/10.1111/bph.14748. G protein-coupled receptors are one of the six major pharmacological targets into which the Guide is divided, with the others being: ion channels, nuclear hormone receptors, catalytic receptors, enzymes and transporters. These are presented with nomenclature guidance and summary information on the best available pharmacological tools, alongside key references and suggestions for further reading. The landscape format of the Concise Guide is designed to facilitate comparison of related targets from material contemporary to mid-2019, and supersedes data presented in the 2017/18, 2015/16 and 2013/14 Concise Guides and previous Guides to Receptors and Channels. It is produced in close conjunction with the International Union of Basic and Clinical Pharmacology Committee on Receptor Nomenclature and Drug Classification (NC-IUPHAR), therefore, providing official IUPHAR classification and nomenclature for human drug targets, where appropriate.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/bph.14748DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6844580PMC
December 2019

THE CONCISE GUIDE TO PHARMACOLOGY 2019/20: Catalytic receptors.

Br J Pharmacol 2019 12;176 Suppl 1:S247-S296

Centre for Discovery Brain Sciences, University of Edinburgh, Edinburgh, EH8 9XD, UK.

The Concise Guide to PHARMACOLOGY 2019/20 is the fourth in this series of biennial publications. The Concise Guide provides concise overviews of the key properties of nearly 1800 human drug targets with an emphasis on selective pharmacology (where available), plus links to the open access knowledgebase source of drug targets and their ligands (www.guidetopharmacology.org), which provides more detailed views of target and ligand properties. Although the Concise Guide represents approximately 400 pages, the material presented is substantially reduced compared to information and links presented on the website. It provides a permanent, citable, point-in-time record that will survive database updates. The full contents of this section can be found at http://onlinelibrary.wiley.com/doi/10.1111/bph.14751. Catalytic receptors are one of the six major pharmacological targets into which the Guide is divided, with the others being: G protein-coupled receptors, ion channels, nuclear hormone receptors, enzymes and transporters. These are presented with nomenclature guidance and summary information on the best available pharmacological tools, alongside key references and suggestions for further reading. The landscape format of the Concise Guide is designed to facilitate comparison of related targets from material contemporary to mid-2019, and supersedes data presented in the 2017/18, 2015/16 and 2013/14 Concise Guides and previous Guides to Receptors and Channels. It is produced in close conjunction with the International Union of Basic and Clinical Pharmacology Committee on Receptor Nomenclature and Drug Classification (NC-IUPHAR), therefore, providing official IUPHAR classification and nomenclature for human drug targets, where appropriate.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/bph.14751DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6844576PMC
December 2019

THE CONCISE GUIDE TO PHARMACOLOGY 2019/20: Ion channels.

Br J Pharmacol 2019 12;176 Suppl 1:S142-S228

Centre for Discovery Brain Science, University of Edinburgh, Edinburgh, EH8 9XD, UK.

The Concise Guide to PHARMACOLOGY 2019/20 is the fourth in this series of biennial publications. The Concise Guide provides concise overviews of the key properties of nearly 1800 human drug targets with an emphasis on selective pharmacology (where available), plus links to the open access knowledgebase source of drug targets and their ligands (www.guidetopharmacology.org), which provides more detailed views of target and ligand properties. Although the Concise Guide represents approximately 400 pages, the material presented is substantially reduced compared to information and links presented on the website. It provides a permanent, citable, point-in-time record that will survive database updates. The full contents of this section can be found at http://onlinelibrary.wiley.com/doi/10.1111/bph.14749. Ion channels are one of the six major pharmacological targets into which the Guide is divided, with the others being: G protein-coupled receptors, nuclear hormone receptors, catalytic receptors, enzymes and transporters. These are presented with nomenclature guidance and summary information on the best available pharmacological tools, alongside key references and suggestions for further reading. The landscape format of the Concise Guide is designed to facilitate comparison of related targets from material contemporary to mid-2019, and supersedes data presented in the 2017/18, 2015/16 and 2013/14 Concise Guides and previous Guides to Receptors and Channels. It is produced in close conjunction with the International Union of Basic and Clinical Pharmacology Committee on Receptor Nomenclature and Drug Classification (NC-IUPHAR), therefore, providing official IUPHAR classification and nomenclature for human drug targets, where appropriate.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/bph.14749DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6844578PMC
December 2019

THE CONCISE GUIDE TO PHARMACOLOGY 2019/20: Enzymes.

Br J Pharmacol 2019 12;176 Suppl 1:S297-S396

Centre for Discovery Brain Sciences, University of Edinburgh, Edinburgh, EH8 9XD, UK.

The Concise Guide to PHARMACOLOGY 2019/20 is the fourth in this series of biennial publications. The Concise Guide provides concise overviews of the key properties of nearly 1800 human drug targets with an emphasis on selective pharmacology (where available), plus links to the open access knowledgebase source of drug targets and their ligands (www.guidetopharmacology.org), which provides more detailed views of target and ligand properties. Although the Concise Guide represents approximately 400 pages, the material presented is substantially reduced compared to information and links presented on the website. It provides a permanent, citable, point-in-time record that will survive database updates. The full contents of this section can be found at http://onlinelibrary.wiley.com/doi/10.1111/bph.14752. Enzymes are one of the six major pharmacological targets into which the Guide is divided, with the others being: G protein-coupled receptors, ion channels, nuclear hormone receptors, catalytic receptors and transporters. These are presented with nomenclature guidance and summary information on the best available pharmacological tools, alongside key references and suggestions for further reading. The landscape format of the Concise Guide is designed to facilitate comparison of related targets from material contemporary to mid-2019, and supersedes data presented in the 2017/18, 2015/16 and 2013/14 Concise Guides and previous Guides to Receptors and Channels. It is produced in close conjunction with the International Union of Basic and Clinical Pharmacology Committee on Receptor Nomenclature and Drug Classification (NC-IUPHAR), therefore, providing official IUPHAR classification and nomenclature for human drug targets, where appropriate.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/bph.14752DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6844577PMC
December 2019
-->