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1.
Dermatol Online J ; 30(2)2024 Apr 15.
Article in English | MEDLINE | ID: mdl-38959927

ABSTRACT

Dermatomyositis (DM) is a multi-organ idiopathic inflammatory myopathy that presents with proximal symmetric muscle weakness accompanied by characteristic cutaneous findings. Most individuals present with skin manifestations prior to muscle involvement and its course can involve the blood vessels, joints, esophagus, and lungs and can be paraneoplastic, making a malignancy assessment imperative. Although its etiology is unknown, type I interferon appears to be a component in evoking the characteristic inflammatory response and patients with DM often have an increase in type I inducible genes. Suspected triggers for DM are environmental factors, drugs, viral infections, and vaccines. The association of DM with vaccination poses a new conundrum within the medical community as people continue to get vaccinated and boosted with SARS-CoV2 vaccines, though it is worth noting that the most common challenges arose as type I hypersensitivity reactions and new onset autoimmune disorders are rare. Presented here is a 53-year-old man who was diagnosed with DM after receiving the second dose of the Pfizer vaccine. His case highlights the importance of the potential onset of autoimmune diseases following the COVID-19 vaccine, a phenomenon that clinicians should be aware of as the discourse concerning the pandemic continues.


Subject(s)
Dermatomyositis , Humans , Dermatomyositis/chemically induced , Male , Middle Aged , COVID-19 Vaccines/adverse effects , BNT162 Vaccine/adverse effects , COVID-19/prevention & control
2.
J Appl Biomech ; 40(1): 14-20, 2024 Feb 01.
Article in English | MEDLINE | ID: mdl-37917960

ABSTRACT

Female athletes exhibit greater rates of anterior cruciate ligament injury compared with male athletes. Biomechanical factors are suggested to contribute to sex differences in injury rates. No previous investigation has evaluated the role of breast support on landing biomechanics. This study investigates the effect of breast support on joint negative work and joint contributions to total negative work during landing. Thirty-five female athletes performed 5 landing trials in 3 breast support conditions. Lower-extremity joint negative work and relative joint contributions to total negative work were calculated. Univariate analyses of variance were used to determine the effect of breast support on negative joint work values. Increasing levels of breast support were associated with lower ankle negative work (P < .001) and ankle relative contributions (P < .001) and increases in hip negative work (P = .008) and hip relative contributions (P < .001). No changes were observed in total negative work (P = .759), knee negative work (P = .059), or knee contributions to negative work (P = .094). These data demonstrate that the level of breast support affects lower-extremity biomechanics. The distal-to-proximal shift in negative joint work and relative joint contributions may be indicative of a more protective landing strategy for anterior cruciate ligament injuries.


Subject(s)
Anterior Cruciate Ligament Injuries , Knee Joint , Humans , Male , Female , Knee , Lower Extremity , Athletes , Biomechanical Phenomena
3.
Inorg Chem ; 61(18): 7032-7042, 2022 May 09.
Article in English | MEDLINE | ID: mdl-35471017

ABSTRACT

Two series of zinc salts, [EtZn][A] and Zn[A]2, with weakly coordinating anions [A]- as counterions have been prepared, and their activities as catalysts for hydrosilylation reactions of 1-hexene, benzophenone, and acetophenone have been investigated. The counterions and per- and partially chlorinated 1-ammonio-closo-dodecaborate anions [Me3NB12Cl11]- [1]-, [Pr3NB12H5Cl6]- [2]-, [Bu3NB12H4Cl7]- [3]-, and [Hex3NB12H5Cl6]- [4]- were chosen as potential and more readily available alternatives to carborate anions such as [CHB11Cl11]- and [HexCB11Cl11]-. The basicity of anion [4]- was determined as being close to that of the triflimide anion [N(SO2CF3)2]-, and the fluoride ion affinities (FIAs) of compounds [EtZn][2] and Zn[2]2 are lower than those of the Lewis acids B(C6F5)3 and Zn[HexCB11Cl11]2. The higher anion basicity and the resulting lower Lewis acidity of the zinc centers result in low activity in 1-hexene hydrosilylation catalysis and only moderate activity in the hydrosilylation catalysis of benzophenone and acetophenone.

4.
Sensors (Basel) ; 22(9)2022 May 06.
Article in English | MEDLINE | ID: mdl-35591223

ABSTRACT

Glucose monitoring technologies allow users to monitor glycemic fluctuations (e.g., blood glucose levels). This is particularly important for individuals who have diabetes mellitus (DM). Traditional self-monitoring blood glucose (SMBG) devices require the user to prick their finger and extract a blood drop to measure the blood glucose based on chemical reactions with the blood. Unlike traditional glucometer devices, noninvasive continuous glucose monitoring (NICGM) devices aim to solve these issues by consistently monitoring users' blood glucose levels (BGLs) without invasively acquiring a sample. In this work, we investigated the feasibility of a novel approach to NICGM using multiple off-the-shelf wearable sensors and learning-based models (i.e., machine learning) to predict blood glucose. Two datasets were used for this study: (1) the OhioT1DM dataset, provided by the Ohio University; and (2) the UofM dataset, created by our research team. The UofM dataset consists of fourteen features provided by six sensors for studying possible relationships between glucose and noninvasive biometric measurements. Both datasets are passed through a machine learning (ML) pipeline that tests linear and nonlinear models to predict BGLs from the set of noninvasive features. The results of this pilot study show that the combination of fourteen noninvasive biometric measurements with ML algorithms could lead to accurate BGL predictions within the clinical range; however, a larger dataset is required to make conclusions about the feasibility of this approach.


Subject(s)
Blood Glucose Self-Monitoring , Wearable Electronic Devices , Algorithms , Blood Glucose , Blood Glucose Self-Monitoring/methods , Glucose , Humans , Machine Learning , Pilot Projects , Wrist
5.
J Org Chem ; 86(9): 6494-6503, 2021 05 07.
Article in English | MEDLINE | ID: mdl-33857378

ABSTRACT

A formal synthesis of the antiviral drug (-)-oseltamivir (Tamiflu) has been accomplished starting from m-anisic acid via a dissolving metal or electrochemical Birch reduction. The correct absolute stereochemistry is efficiently set through enzyme-catalyzed carbonyl reduction on the resultant racemic α,ß-unsaturated ketone. A screen of a broad ketoreductase (KRED) library identified several that deliver the desired allylic alcohol with nearly perfect facial selectivity at the new center for each antipodal substrate, indicating that the enzyme also is able to completely override inherent diastereomeric bias in the substrate. Conversion is complete, with d-glucose serving as the terminal hydride donor (glucose dehydrogenase). For each resulting diastereomeric secondary alcohol, O/N-interconversion is then efficiently effected either by synfacial [3,3]-sigmatropic allylic imidate rearrangement or by direct, stereoinverting N-Mitsunobu chemistry. Both stereochemical outcomes have been confirmed crystallographically. The α,ß-unsaturation is then introduced via an α-phenylselenylation/oxidation/pyrolysis sequence to yield the targeted (S)-N-acyl-protected 5-amino-1,3-cyclohexadiene carboxylates, key advanced intermediates for oseltamivir pioneered by Corey (N-Boc) and Trost (N-phthalamido), respectively.


Subject(s)
Alcohols , Oseltamivir , Antiviral Agents , Oxidation-Reduction , Stereoisomerism
6.
Scand J Med Sci Sports ; 31(2): 380-387, 2021 Feb.
Article in English | MEDLINE | ID: mdl-33080072

ABSTRACT

Recently, we proposed the hypothesis that weekly running volume and preferred running pace may play a role in preserving ankle joint kinetics in middle-age runners as ankle joint kinetics were generally similar in young and middle-aged runners with similar running volume and preferred pace. To further address this hypothesis, we compared lower extremity joint kinetics between high and low training volume runners in both young and middle-aged groups. Joint kinetics calculated from 3D kinematic and ground reaction force data during over-ground running at 2.7 m·s-1 from young and middle-aged runners who ran low or high weekly volume were analyzed. A two-factor analysis of variance was used to compare joint kinetics between age and running volume groups. Positive hip work was greater in middle-aged compared to young runners (P = .005). Plantarflexor torque (P = .009) and positive ankle work (P = .042) were greater in young compared to middle-aged runners. Positive ankle work was also greater in the high compared to the low volume group (P = .021). Finally, age by volume interactions were found for knee extensor torque (P = .024), negative knee work (P = .018), and positive knee work (P = .019) but not for ankle and hip joint kinetics. These findings suggest less distal-to-proximal difference in positive joint work with high running volume in both young and middle-aged runners as a result of greater power generation at the ankle. Given the age main effects, our findings are also the first to suggest the age-related distal-to-proximal shift in joint kinetics appears in middle-aged runners.


Subject(s)
Age Factors , Ankle Joint/physiology , Biomechanical Phenomena/physiology , Hip Joint/physiology , Knee Joint/physiology , Running/physiology , Running/statistics & numerical data , Adult , Analysis of Variance , Body Mass Index , Female , Humans , Male , Middle Aged , Time Factors , Torque
7.
J Strength Cond Res ; 35(3): 616-625, 2021 Mar 01.
Article in English | MEDLINE | ID: mdl-33587546

ABSTRACT

ABSTRACT: Daugherty, HJ, Weiss, LW, Paquette, MR, Powell, DW, and Allison, LE. Potential predictors of vertical jump performance: Lower extremity dimensions and alignment, relative body fat, and kinetic variables. J Strength Cond Res 35(3): 616-625, 2021-The association of structural and kinetic variables with restricted vertical jump (RVJ) displacement without and with added mass was examined in 60 men and women. Added mass (weighted vest) simulated a 5% increase in body fat (BF%). Independent variables included BF%, thigh length, and static Q-angle (Q-angles), and while performing RVJ, different expressions of frontal-plane knee angle (FPKA), dynamic Q-angle (Q-angled), vertical ground reaction force (vGRF), concentric vertical impulse (Iz), concentric rate of force development (CRFD), and vertical power (Pz). Variables having significant (p ≤ 0.05) negative correlations with RVJ displacement included BF% (r = -0.76) and Q-angles (r = -0.55). Those having significant (p ≤ 0.05) positive correlations with RVJ displacement included peak and average concentric Pz (r range = 0.74-0.81), peak and average concentric vGRF (r range = 0.46-0.67), Iz (r range = 0.32-0.54), thigh length (r = 0.31), minimum Q-angled (r = 0.31), and maximum FPKA (r = 0.28). Variables not associated (p > 0.05) with RVJ displacement included minimum and excursion FPKA (r = 0.11 and 0.23), maximum, excursion, and average Q-angled (r = 0.24, 0.11, and 0.22), and CRFD (r range = 0.19-0.24). A simple regression model predicted RVJ displacement (p = 1.00) for the simulated 5% increase in body fat. To maximize jumping performance, (a) high levels of body fat should be avoided, (b) peak and average Pz, vGRF, and Iz should be maximized through training, and (c) having a lower Q-angles is associated with better jumping ability.


Subject(s)
Knee , Lower Extremity , Adipose Tissue , Biomechanical Phenomena , Female , Humans , Kinetics , Knee Joint , Male
8.
Inorg Chem ; 59(8): 5433-5446, 2020 Apr 20.
Article in English | MEDLINE | ID: mdl-32237741

ABSTRACT

A group of copper complexes supported by polydentate pyridylamide ligands H2bpda and H2ppda were synthesized and characterized. The two Cu(II) dimers [CuII2(Hbpda)2(ClO4)2] (1) and [CuII2(ppda)2(DMF)2] (2) were constructed by using neutral ligands to react with Cu(II) salts. Although the dimers showed similar structural features, the second-sphere interactions affect the structures differently. With the application of Et3N, the tetranuclear cluster (HNEt3)[CuII4(bpda)2(µ3-OH)2(ClO4)(DMF)3](ClO4)2 (3) and hexanuclear cluster (HNEt3)2[CuII6(ppda)6(H2O)2(CH3OH)2](ClO4)2 (4) were prepared under similar reaction conditions. The symmetrical and unsymmetrical arrangement of the ligand donors in ligands H2bpda and H2ppda led to the dramatic conformation difference of the two Cu(II) complexes. As part of our effort to explore mixed-valence copper chemistry, the triple-decker pentanuclear cluster [CuII3CuI2(bpda)3(µ3-O)] (5) was prepared. XPS examination demonstrated the localized mixed-valence properties of complex 5. Magnetic studies of the clusters with EPR evidence showed either weak ferromagnetic or antiferromagnetic interactions among copper centers. Due to the trigonal-planar conformation of the trinuclear Cu(II) motif with the µ3-O center, complex 5 exhibits geometric spin frustration and engages in antisymmetric exchange interactions. DFT calculations were also performed to better interpret spectroscopic evidence and understand the electronic structures, especially the mixed-valence nature of complex 5.

9.
J Am Acad Dermatol ; 83(6): 1730-1737, 2020 Dec.
Article in English | MEDLINE | ID: mdl-32707253

ABSTRACT

The recent COVID-19 pandemic has resulted in increased hand hygiene and hand cleansing awareness. To prevent virus transmission, the Centers for Disease Control and Prevention recommends frequent hand washing with soap and water. Hand hygiene products are available in a variety of forms, and while each of these formulations may be effective against COVID-19, they may also alter skin barrier integrity and function. As health care workers and the general population focus on stringent hand hygiene, the American Contact Dermatitis Society anticipates an increase in both irritant contact and allergic contact hand dermatitis. Alcohol-based hand sanitizers with moisturizers have the least sensitizing and irritancy potential when compared to soaps and synthetic detergents. This article provides an overview of the most frequently used hand hygiene products and their associations with contact dermatitis as well as recommendations from the American Contact Dermatitis Society on how to treat and prevent further dermatitis.


Subject(s)
Dermatitis, Contact/prevention & control , Dermatitis, Occupational/prevention & control , Hand Dermatoses/prevention & control , Hand Hygiene/standards , Practice Guidelines as Topic , Anti-Infective Agents, Local/administration & dosage , Anti-Infective Agents, Local/adverse effects , Betacoronavirus/pathogenicity , COVID-19 , Communicable Disease Control/methods , Communicable Disease Control/standards , Coronavirus Infections/epidemiology , Coronavirus Infections/prevention & control , Coronavirus Infections/transmission , Coronavirus Infections/virology , Dermatitis, Contact/etiology , Dermatitis, Occupational/etiology , Hand Dermatoses/chemically induced , Health Personnel , Humans , Irritants/administration & dosage , Irritants/adverse effects , Pandemics/prevention & control , Pneumonia, Viral/epidemiology , Pneumonia, Viral/prevention & control , Pneumonia, Viral/transmission , Pneumonia, Viral/virology , SARS-CoV-2 , Soaps/adverse effects , Societies, Medical/standards , United States
10.
J Nat Prod ; 83(7): 2269-2280, 2020 07 24.
Article in English | MEDLINE | ID: mdl-32649211

ABSTRACT

Triple-negative breast cancers (TNBC) are aggressive and heterogeneous cancers that lack targeted therapies. We implemented a screening program to identify new leads for subgroups of TNBC using diverse cell lines with different molecular drivers. Through this program, we identified an extract from Calotropis gigantea that caused selective cytotoxicity in BT-549 cells as compared to four other TNBC cell lines. Bioassay-guided fractionation of the BT-549 selective extract yielded nine cardenolides responsible for the selective activity. These included eight known cardenolides and a new cardenolide glycoside. Structure-activity relationships among the cardenolides demonstrated a correlation between their relative potencies toward BT-549 cells and Na+/K+ ATPase inhibition. Calotropin, the compound with the highest degree of selectivity for BT-549 cells, increased intracellular Ca2+ in sensitive cells to a greater extent than in the resistant MDA-MB-231 cells. Further studies identified a second TNBC cell line, Hs578T, that is also highly sensitive to the cardenolides, and mechanistic studies were conducted to identify commonalities among the sensitive cell lines. Experiments showed that both cardenolide-sensitive cell lines expressed higher mRNA levels of the Na+/Ca2+ exchanger NCX1 than resistant TNBC cells. This suggests that NCX1 could be a biomarker to identify TNBC patients that might benefit from the clinical administration of a cardiac glycoside for anticancer indications.


Subject(s)
Antineoplastic Agents, Phytogenic/pharmacology , Calotropis/chemistry , Cardenolides/pharmacology , Triple Negative Breast Neoplasms/pathology , Biomarkers, Tumor/metabolism , Calcium/metabolism , Cardenolides/chemistry , Cell Line, Tumor , Drug Screening Assays, Antitumor , Enzyme Inhibitors/pharmacology , Female , Humans , Molecular Structure , Sodium-Potassium-Exchanging ATPase/antagonists & inhibitors , Structure-Activity Relationship , Triple Negative Breast Neoplasms/metabolism
11.
J Biomech Eng ; 142(5)2020 05 01.
Article in English | MEDLINE | ID: mdl-31769785

ABSTRACT

Patients who sustain irreversible cartilage damage or joint instability from ankle injuries are likely to develop ankle osteoarthritis (OA). A dynamic ankle orthosis (DAO) was recently designed with the intent to offload the foot and ankle using a distractive force, allowing more natural sagittal and frontal plane ankle motion during gait. To evaluate its efficacy, this study compared ankle joint kinematics and plantar pressures among the DAO, standard double upright ankle-foot orthosis (DUAFO), and a nonorthosis control (CON) condition in healthy adults during walking. Ten healthy subjects (26 ± 3.8 yr; 69.6 ± 12.7 kg; and 1.69 ± 0.07 m) walked on a treadmill at 1.4 m/s in three orthosis conditions: CON, DAO, and DUAFO. Ankle kinematics were assessed using a three-dimensional (3D) motion capture system and in-shoe plantar pressures were measured for seven areas of the foot. DAO reduced hallux peak plantar pressures (PPs) compared to CON and DUAFO. PPs under toes 2-5 were smaller in DAO than DUAFO, but greater in DUAFO compared to CON. Early stance peak plantarflexion (PF) angular velocity was smaller in DAO compared to CON and DUAFO. Eversion (EV) ROM was much smaller in DUAFO compared to CON and DAO. Early stance peak eversion angular velocity was smaller in DAO and much smaller in DUAFO compared to CON. This study demonstrates the capacity of the DAO to provide offloading during ambulation without greatly affecting kinematic parameters including frontal plane ankle motion compared to CON. Future work will assess the effectiveness of the DAO in a clinical osteoarthritic population.


Subject(s)
Ankle Joint , Foot Orthoses , Adult , Ankle , Biomechanical Phenomena , Humans , Middle Aged , Walking
12.
J Strength Cond Res ; 34(6): 1634-1642, 2020 Jun.
Article in English | MEDLINE | ID: mdl-29979276

ABSTRACT

Smith, RE, Paquette, MR, Harry, JR, Powell, DW, and Weiss, LW. Footwear and sex differences in performance and joint kinetics during maximal vertical jumping. J Strength Cond Res 34(6): 1634-1642, 2020-This investigation examined the effects of footwear and sex on vertical jump displacement and joint power contributions. Twenty-three young adults with basketball experience performed 3 maximal countermovement vertical jumps in minimal and standard footwear. Ground reaction force and 3D kinematic data were collected during jumping. Footwear by sex analysis of variance for all dependent variables and effect sizes (d) was computed. An interaction effect showed that men produced greater lower-limb-positive work than women in standard footwear. Men jumped higher than women (d = 2.53) and produced greater peak ankle, knee and hip joint moments (d > 0.99), positive joint powers (d > 1.07) and, positive knee and hip joint work (d > 1.04) with no sex differences for negative joint powers and work (p > 0.05). Minimal footwear produced less peak-positive knee power (d = 0.27) and less positive ankle (d = 0.34) and knee (d = 0.21) joint work than standard footwear. Because negative joint power and work were similar between sexes, men may be better able to use the stretch-shortening cycle compared with women. Higher joint mechanical demands may provide a better vertical jumping training stimulus in standard compared with minimal footwear. Future studies should investigate footwear training effects on performance and joint mechanics during jumping.


Subject(s)
Athletic Performance/physiology , Basketball/physiology , Sex Characteristics , Shoes , Adolescent , Adult , Ankle Joint/physiology , Biomechanical Phenomena , Female , Hip Joint/physiology , Humans , Knee Joint/physiology , Lower Extremity/physiology , Male , Young Adult
13.
J Appl Biomech ; 36(3): 126-133, 2020 Jun 01.
Article in English | MEDLINE | ID: mdl-32126525

ABSTRACT

Aging is associated with a distal-to-proximal shift in joint kinetics during walking. This plasticity of gait is amplified rather than attenuated in old adults with high physical capacity. Because running is associated with greater kinetic demands at the ankle, older individuals with more versus less lifetime running exposure may retain a larger proportion of their ankle kinetics. The purpose of the study was to compare lower-extremity joint kinetics during walking between middle-aged runners with high and low lifetime running exposure. Eighteen middle-aged runners (9 per group) participated. Joint kinetics were calculated from kinematic and ground reaction force data during overground walking at 1.3 m·s-1 and compared between groups. High exposure runners produced 50% greater positive hip work (P = .03; Cohen d = 1.02) during walking compared with low exposure runners, but ankle kinetics were not different between groups. No other differences in joint kinetics or kinematics were observed between groups. These findings suggest that the age-related increase in hip joint kinetics during walking could be a compensatory gait strategy that is not attenuated by lifetime running exposure alone. Finally, the amount of lifetime running exposure did not affect ankle kinetics during walking in middle-aged runners.

14.
Inorg Chem ; 58(18): 12441-12445, 2019 Sep 16.
Article in English | MEDLINE | ID: mdl-31453691

ABSTRACT

Although gallium hydrides XnGaH3-n (X = monoanionic substituent) are usually stable compounds, cationic arene-solvated species [H2Ga(arene)2]+ spontaneously eliminate dihydrogen at room temperature to afford the arene-solvated gallium(I) compounds [Ga(PhF)2][CHB11Cl11] (1) and [Ga(Ph3CH)][B(C6F5)4] (3). A key requirement appears to be the presence of a weakly coordinating anion. Use of the more basic triflimide anion, [NTf2]-, reverses the stability, i.e., the gallium(III) hydride H2GaNTf2 (4) is more stable than the gallium(I) compound GaNTf2 (5). The experimental results are supported by DFT calculations. Compounds 1 and 3 can be used as catalysts for the oligomerization of 2,4,4-trimethyl-1-pentene and the hydrosilylation of benzophenone and 1-hexene.

15.
Semin Speech Lang ; 40(1): 48-56, 2019 Feb.
Article in English | MEDLINE | ID: mdl-30616294

ABSTRACT

Postural instability is a cardinal indicator of concussion. Assessments of the postural control system range from clinical to laboratory tests that assess the balance of the individual. In a previous article regarding clinical assessment of balance in adults with concussion, we reviewed the importance of balance as a component in concussion evaluations. The purpose of this review article is to update the information previously published in 2014. Since 2014, research has provided evidence for the incorporation of dynamic methods for evaluating balance postconcussion with particular emphasis on sensory system integration and dual tasking. Therefore, this review will examine the current state of knowledge on how concussion injuries affect postural control, advancements in evaluating balance postconcussion, such as novel eye-tracking techniques, and current recommendations for best practices for balance assessment.


Subject(s)
Brain Concussion/diagnosis , Neurologic Examination/methods , Postural Balance , Sensation Disorders/diagnosis , Adult , Exercise Therapy , Follow-Up Studies , Humans , Meniere Disease/diagnosis , Meniere Disease/etiology , Vestibule, Labyrinth/injuries
16.
Angew Chem Int Ed Engl ; 58(51): 18598-18603, 2019 12 16.
Article in English | MEDLINE | ID: mdl-31591802

ABSTRACT

Some bacterial heme proteins catalyze the coupling of two NO molecules to generate N2 O. We previously reported that a heme Fe-NO model engages in this N-N bond-forming reaction with NO. We now demonstrate that (OEP)CoII (NO) similarly reacts with 1 equiv of NO in the presence of the Lewis acids BX3 (X=F, C6 F5 ) to generate N2 O. DFT calculations support retention of the CoII oxidation state for the experimentally observed adduct (OEP)CoII (NO⋅BF3 ), the presumed hyponitrite intermediate (P.+ )CoII (ONNO⋅BF3 ), and the porphyrin π-radical cation by-product of this reaction, and that the π-radical cation formation likely occurs at the hyponitrite stage. In contrast, the Fe analogue undergoes a ferrous-to-ferric oxidation state conversion during this reaction. Our work shows that cobalt hemes are chemically competent to engage in the NO-to-N2 O conversion reaction.


Subject(s)
Cobalt/chemistry , Heme/chemistry , Iron/chemistry , Lewis Acids/chemistry , Nitric Oxide/chemistry , X-Ray Diffraction/methods , Humans , Molecular Structure
17.
J Am Chem Soc ; 140(12): 4204-4207, 2018 03 28.
Article in English | MEDLINE | ID: mdl-29502400

ABSTRACT

Bacterial NO reductase (bacNOR) enzymes utilize a heme/non-heme active site to couple two NO molecules to N2O. We show that BF3 coordination to the nitrosyl O-atom in (OEP)Fe(NO) activates it toward N-N bond formation with NO to generate N2O. 15N-isotopic labeling reveals a reversible nitrosyl exchange reaction and follow-up N-O bond cleavage in the N2O formation step. Other Lewis acids (B(C6F5)3 and K+) also promote the NO coupling reaction with (OEP)Fe(NO). These results, complemented by DFT calculations, provide experimental support for the cis: b3 pathway in bacNOR.


Subject(s)
Ferrous Compounds/chemistry , Heme/chemistry , Lewis Acids/chemistry , Nitric Oxide/chemistry , Nitrous Oxide/chemical synthesis , Nitrous Oxide/chemistry , Quantum Theory
18.
J Strength Cond Res ; 32(12): 3416-3422, 2018 Dec.
Article in English | MEDLINE | ID: mdl-28240709

ABSTRACT

Powell, DW and Williams, DSB. Changes in vertical and joint stiffness in runners with advancing age. J Strength Cond Res 32(12): 3425-3431, 2018-Age-related changes in the neuromuscular system underlie reduced performance and injury but may be mitigated through regular physical activity. It was hypothesized that older (OLD) compared with young (YOUNG) adults would exhibit greater vertical and joint stiffness when running at 3.35 m·s. Nine YOUNG and 10 OLD runners performed over ground running trials while three-dimensional biomechanics were recorded. Ankle and knee joint angles, moments and stiffness values were compared between YOUNG & OLD. YOUNG had smaller vertical stiffness (p = 0.01; YOUNG: 32.8 ± 3.6; OLD: 38.1 ± 5.7) and greater joint stiffness than OLD at the ankle (p = 0.04; YOUNG: 0.134 ± 0.021; OLD: 0.118 ± 0.017) and knee (p = 0.01; YOUNG: 0.119 ± 0.016; OLD: 0.098 ± 0.014). YOUNG exhibited greater peak knee flexion angles (p = 0.04; YOUNG: 43.4 ± 6.5°; OLD: 39.1 ± 2.6°), and peak ankle plantarflexion (p = 0.02; YOUNG: -2.8 ± 0.4 Nm·kg; OLD: -2.5 ± 0.1 Nm·kg) and knee extension moments (p < 0.01; 2.6 ± 0.3 Nm·kg; OLD: 2.1 ± 0.2 Nm·kg) than OLD whereas no differences were observed in peak ankle dorsiflexion angles (p = 0.44; YOUNG: 23.6 ± 4.2°; OLD: 23.4 ± 2.1°). The findings of this study suggest that OLD compared with YOUNG adults adopt altered lower extremity biomechanics. These altered running biomechanics by seek to minimize the metabolic cost of running or may be a function of reduced lower extremity strength and power.


Subject(s)
Age Factors , Ankle Joint/physiology , Knee Joint/physiology , Range of Motion, Articular , Running/physiology , Adult , Aged , Ankle Joint/physiopathology , Biomechanical Phenomena , Humans , Knee Joint/physiopathology , Lower Extremity , Middle Aged
19.
J Am Chem Soc ; 139(28): 9495-9498, 2017 07 19.
Article in English | MEDLINE | ID: mdl-28648069

ABSTRACT

The conversion of inorganic NOx species to organo-N compounds is an important component of the global N-cycle. Reaction of a C-based nucleophile, namely the phenyl anion, with the ferric heme nitrosyl [(OEP)Fe(NO)(5-MeIm)]+ generates a mixture of the C-nitroso derivative (OEP)Fe(PhNO)(5-MeIm) and (OEP)Fe(Ph). The related reaction with [(OEP)Ru(NO)(5-MeIm)]+ generates the (OEP)Ru(PhNO)(5-MeIm) product. Reactions with the N-based nucleophile diethylamide results in the formation of free diethylnitrosamine, whereas the reaction with azide results in N2O formation; these products derive from attack of the nucleophiles on the bound NO groups. These results provide the first demonstrations of C-N and N-N bond formation from attack of C-based and N-based nucleophiles on synthetic ferric-NO hemes.

20.
J Nat Prod ; 80(3): 598-608, 2017 03 24.
Article in English | MEDLINE | ID: mdl-28335605

ABSTRACT

Few secondary metabolites have been reported from mammalian microbiome bacteria despite the large numbers of diverse taxa that inhabit warm-blooded higher vertebrates. As a means to investigate natural products from these microorganisms, an opportunistic sampling protocol was developed, which focused on exploring bacteria isolated from roadkill mammals. This initiative was made possible through the establishment of a newly created discovery pipeline, which couples laser ablation electrospray ionization mass spectrometry (LAESIMS) with bioassay testing, to target biologically active metabolites from microbiome-associated bacteria. To illustrate this process, this report focuses on samples obtained from the ear of a roadkill opossum (Dideiphis virginiana) as the source of two bacterial isolates (Pseudomonas sp. and Serratia sp.) that produced several new and known cyclic lipodepsipeptides (viscosin and serrawettins, respectively). These natural products inhibited biofilm formation by the human pathogenic yeast Candida albicans at concentrations well below those required to inhibit yeast viability. Phylogenetic analysis of 16S rRNA gene sequence libraries revealed the presence of diverse microbial communities associated with different sites throughout the opossum carcass. A putative biosynthetic pathway responsible for the production of the new serrawettin analogues was identified by sequencing the genome of the Serratia sp. isolate. This study provides a functional roadmap to carrying out the systematic investigation of the genomic, microbiological, and chemical parameters related to the production of natural products made by bacteria associated with non-anthropoidal mammalian microbiomes. Discoveries emerging from these studies are anticipated to provide a working framework for efforts aimed at augmenting microbiomes to deliver beneficial natural products to a host.


Subject(s)
Biological Products/chemistry , Lipoproteins/chemistry , Microbiota , Peptides, Cyclic/chemistry , Pseudomonas/chemistry , RNA, Ribosomal, 16S/genetics , Serratia/chemistry , Animals , Animals, Wild , Genetic Variation , Humans , Mammals , Molecular Structure , Nuclear Magnetic Resonance, Biomolecular , Phylogeny , Spectrometry, Mass, Electrospray Ionization , Vertebrates
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