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1.
FASEB J ; 38(5): e23518, 2024 Mar 15.
Article in English | MEDLINE | ID: mdl-38441532

ABSTRACT

NUDC (nuclear distribution protein C) is a mitotic protein involved in nuclear migration and cytokinesis across species. Considered a cytoplasmic dynein (henceforth dynein) cofactor, NUDC was shown to associate with the dynein motor complex during neuronal migration. NUDC is also expressed in postmitotic vertebrate rod photoreceptors where its function is unknown. Here, we examined the role of NUDC in postmitotic rod photoreceptors by studying the consequences of a conditional NUDC knockout in mouse rods (rNudC-/- ). Loss of NUDC in rods led to complete photoreceptor cell death at 6 weeks of age. By 3 weeks of age, rNudC-/- function was diminished, and rhodopsin and mitochondria were mislocalized, consistent with dynein inhibition. Levels of outer segment proteins were reduced, but LIS1 (lissencephaly protein 1), a well-characterized dynein cofactor, was unaffected. Transmission electron microscopy revealed ultrastructural defects within the rods of rNudC-/- by 3 weeks of age. We investigated whether NUDC interacts with the actin modulator cofilin 1 (CFL1) and found that in rods, CFL1 is localized in close proximity to NUDC. In addition to its potential role in dynein trafficking within rods, loss of NUDC also resulted in increased levels of phosphorylated CFL1 (pCFL1), which would purportedly prevent depolymerization of actin. The absence of NUDC also induced an inflammatory response in Müller glia and microglia across the neural retina by 3 weeks of age. Taken together, our data illustrate the critical role of NUDC in actin cytoskeletal maintenance and dynein-mediated protein trafficking in a postmitotic rod photoreceptor.


Subject(s)
Actins , Dyneins , Animals , Mice , Biological Transport , Cell Death , Dyneins/genetics , Retinal Rod Photoreceptor Cells
2.
bioRxiv ; 2023 Nov 29.
Article in English | MEDLINE | ID: mdl-38076848

ABSTRACT

NUDC ( nu clear d istribution protein C) is a mitotic protein involved in nuclear migration and cytokinesis across species. Considered a cytoplasmic dynein (henceforth dynein) cofactor, NUDC was shown to associate with the dynein motor complex during neuronal migration. NUDC is also expressed in postmitotic vertebrate rod photoreceptors where its function is unknown. Here, we examined the role of NUDC in postmitotic rod photoreceptors by studying the consequences of a conditional NUDC knockout in mouse rods (r NudC -/- ). Loss of NUDC in rods led to complete photoreceptor cell death at six weeks of age. By 3 weeks of age, r NudC -/- function was diminished, and rhodopsin and mitochondria were mislocalized, consistent with dynein inhibition. Levels of outer segment proteins were reduced, but LIS1 (lissencephaly protein 1), a well-characterized dynein cofactor, was unaffected. Transmission electron microscopy revealed ultrastructural defects within the rods of r NudC -/- by 3 weeks of age. We investigated whether NUDC interacts with the actin modulator cofilin 1 (CFL1) and found that in rods, CFL1 is localized in close proximity to NUDC. In addition to its potential role in dynein trafficking within rods, loss of NUDC also resulted in increased levels of phosphorylated CFL1 (pCFL1), which would purportedly prevent depolymerization of actin. Absence of NUDC also induced an inflammatory response in Müller glia and microglia across the neural retina by 3 weeks of age. Taken together, our data illustrate the critical role of NUDC in actin cytoskeletal maintenance and dynein-mediated protein trafficking in a postmitotic rod photoreceptor. Significance Statement: Nuclear distribution protein C (NUDC) has been studied extensively as an essential protein for mitotic cell division. In this study, we discovered its expression and role in the postmitotic rod photoreceptor cell. In the absence of NUDC in mouse rods, we detected functional loss, protein mislocalization, and rapid retinal degeneration consistent with dynein inactivation. In the early phase of retinal degeneration, we observed ultrastructural defects and an upregulation of inflammatory markers suggesting additional, dynein-independent functions of NUDC.

3.
Invest Ophthalmol Vis Sci ; 64(15): 19, 2023 Dec 01.
Article in English | MEDLINE | ID: mdl-38099735

ABSTRACT

Purpose: To examine deformations of the optic nerve head (ONH) deep tissues in response to acute elevation of intraocular pressure (IOP). Methods: Research-consented brain-dead organ donors underwent imaging by spectral domain optical coherence tomography (OCT). OCT imaging was repeated while the eye was sequentially maintained at manometric pressures of 10, 30, and 50 mm Hg. Radial scans of the ONH were automatically segmented by deep learning and quantified in three dimensions by a custom algorithm. Change in lamina cribrosa (LC) depth and choroidal thickness was correlated with IOP and age by linear mixed-effect models. LC depth was computed against commonly utilized reference planes. Results: Twenty-six eyes from 20 brain-dead organ donors (age range, 22-62 years; median age, 43 years) were imaged and quantified. LC depth measured against a reference plane based on Bruch's membrane (BM), BM opening, and an anterior sclera canal opening plane showed both a reduction and an increase in LC depth with IOP elevation. LC depth universally increased in depth when measured against a sclera reference plane. Choroidal (-0.5222 µm/mm Hg, P < 0.001) and retinal nerve fiber layer thickness (-0.0717 µm/mm Hg, P < 0.001) significantly thinned with increasing IOP. The magnitude of LC depth change with IOP was significantly smaller with increasing age (P < 0.03 for all reference planes). Conclusions: LC depth changes with IOP reduce with age and are significantly affected by the reference plane of choice, which highlights a need for standardizing LC metrics to properly follow progressive remodeling of the loadbearing tissues of the ONH by OCT imaging and for the definition of a reference database.


Subject(s)
Intraocular Pressure , Optic Disk , Tonometry, Ocular , Bruch Membrane , Brain
4.
Exp Eye Res ; 229: 109420, 2023 04.
Article in English | MEDLINE | ID: mdl-36806673

ABSTRACT

PURPOSE: The relationships between intraocular pressure (IOP), ocular perfusion pressure (OPP), retinal perfusion, and retinal electrophysiologic responses have been explored experimentally across several animal models. These studies have demonstrated that elevated IOP reduces OPP, and when this reduction in OPP exceeds the autoregulatory capacity of the retina vasculature, retinal perfusion and electrophysiologic responses are reduced. This study aimed to evaluate these interactions for the first time in the living human eye. METHODS: Five eyes from three research-consented brain-dead organ donors underwent optical coherence tomography with angiographic (OCT/A; Spectralis, Heidelberg Engineering) and electroretinographic (ERG, Diagnosys LLC) measurements while IOP was manometrically-elevated stepwise to pressures of 10, 30 and 50 mmHg. Systemic blood pressure (BP) was monitored continuously during testing. Correlation analysis was applied to assess association between ERG and OPP changes. In a single eye, prolonged IOP elevation was induced with viscoelastic injection and serial ERG measurements were obtained. RESULTS: Reductions in inner retinal function defined by photopic ERG were observed with elevation in IOP and concomitant reduction in OPP. Reductions, especially in b-wave, and photopic negative response (PhNR) amplitudes and implicit times were significantly correlated with elevation in IOP and reduction in OPP. There were more appreciable changes in perfusion and functional responses in eyes tested while systemic blood pressure was lower. With prolonged IOP elevation, selective loss of the PhNR response was observed. CONCLUSIONS: In the living human eye, retinal perfusion and inner retinal function are acutely impacted by elevation of IOP, and this impact is related to systemic BP and OPP. This novel approach provides a viable model to study the autoregulatory responses to IOP elevation in the living human eye.


Subject(s)
Glaucoma , Ocular Hypertension , Animals , Humans , Intraocular Pressure , Retina , Tonometry, Ocular , Electroretinography/methods
5.
Int J Mol Sci ; 23(15)2022 Jul 22.
Article in English | MEDLINE | ID: mdl-35897642

ABSTRACT

Glaucomatous optic neuropathy is the leading cause of irreversible blindness in the world. The chronic disease is characterized by optic nerve degeneration and vision field loss. The reduction of intraocular pressure remains the only proven glaucoma treatment, but it does not prevent further neurodegeneration. There are three major classes of cells in the human optic nerve head (ONH): lamina cribrosa (LC) cells, glial cells, and scleral fibroblasts. These cells provide support for the LC which is essential to maintain healthy retinal ganglion cell (RGC) axons. All these cells demonstrate responses to glaucomatous conditions through extracellular matrix remodeling. Therefore, investigations into alternative therapies that alter the characteristic remodeling response of the ONH to enhance the survival of RGC axons are prevalent. Understanding major remodeling pathways in the ONH may be key to developing targeted therapies that reduce deleterious remodeling.


Subject(s)
Glaucoma , Optic Disk , Optic Nerve Diseases , Glaucoma/metabolism , Glaucoma/therapy , Humans , Intraocular Pressure , Optic Disk/metabolism , Optic Nerve Diseases/metabolism , Retinal Ganglion Cells
6.
Front Ophthalmol (Lausanne) ; 2: 1007103, 2022.
Article in English | MEDLINE | ID: mdl-38983517

ABSTRACT

The maintenance of intraocular pressure (IOP) is critical to preserving the pristine optics required for vision. Disturbances in IOP can directly impact the optic nerve and retina, and inner retinal injury can occur following acute and chronic IOP elevation. There are a variety of animal models that have been developed to study the effects of acute and chronic elevation of IOP on the retina, retinal ganglion cell (RGC) morphology, intracellular signaling, gene expression changes, and survival. Acute IOP models induce injury that allows for the study of RGC response to well characterized injury and potential recovery. This review will focus on the initial impact of acute IOP elevation on RGC injury and recovery as these early responses may be the best targets for potential therapeutic interventions to promote RGC survival in glaucoma.

7.
Int J Sports Phys Ther ; 16(5): 1190-1209, 2021.
Article in English | MEDLINE | ID: mdl-34631241

ABSTRACT

BACKGROUND: Deficits in dynamic neuromuscular control have been associated with post-injury sequelae and increased injury risk. The Y-Balance Test Lower Quarter (YBT-LQ) has emerged as a tool to identify these deficits. PURPOSE: To review the reliability of the YBT-LQ, determine if performance on the YBT-LQ varies among populations (i.e., sex, sport/activity, and competition level), and to determine the injury risk identification validity of the YBT-LQ based on asymmetry, individual reach direction performance, or composite score. STUDY DESIGN: Systematic Review. METHODS: A comprehensive search was performed of 10 online databases from inception to October 30, 2019. Only studies that tested dynamic single leg balance using the YBT-LQ were included. Studies were excluded if the Y-Balance Test kit was not utilized during testing or if there was a major deviation from the Y-Balance test procedure. For methodological quality assessment, the modified Downs and Black scale and the Newcastle-Ottawa Scale were used. RESULTS: Fifty-seven studies (four in multiple categories) were included with nine studies assessing reliability, 36 assessing population differences, and 16 assessing injury prediction were included. Intra-rater reliability ranged from 0.85-0.91. Sex differences were observed in the posteromedial direction (males: 109.6 [95%CI 107.4-111.8]; females: 102.3 [95%CI 97.2-107.4; p = 0.01]) and posterolateral direction (males: 107.0 [95%CI 105.0-109.1]; females: 102.0 [95%CI 97.8-106.2]). However, no difference was observed between sexes in the anterior reach direction (males: 71.9 [95%CI 69.5-74.5]; females: 70.8 [95%CI 65.7-75.9]; p=0.708). Differences in composite score were noted between soccer (97.6; 95%CI 95.9-99.3) and basketball (92.8; 95%CI 90.4-95.3; p <0.01), and baseball (97.4; 95%CI 94.6-100.2) and basketball (92.8; 95%CI 90.4-95.3; p=0.02). Given the heterogeneity of injury prediction studies, a meta-analysis of these data was not possible. Three of the 13 studies reported a relationship between anterior reach asymmetry reach and injury risk, three of 10 studies for posteromedial and posterolateral reach asymmetry, and one of 13 studies reported relationship with composite reach asymmetry. CONCLUSIONS: There was moderate to high quality evidence demonstrating that the YBT-LQ is a reliable dynamic neuromuscular control test. Significant differences in sex and sport were observed. If general cut points (i.e., not population specific) are used, the YBT-LQ may not be predictive of injury. Clinical population specific requirements (e.g., age, sex, sport/activity) should be considered when interpreting YBT-LQ performance, particularly when used to identify risk factors for injury. LEVEL OF EVIDENCE: 1b.

9.
Int J Sports Phys Ther ; 16(2): 306-311, 2021 Apr 01.
Article in English | MEDLINE | ID: mdl-33842026

ABSTRACT

BACKGROUND: Limited ankle dorsiflexion (DF) is associated with ankle sprains and other lower extremity injuries. Current ankle measurements can be laborious to perform in an athletic environment. PURPOSE: The purpose of this study was to determine the reliability and discriminant validity of a novel closed-chain ankle DF ROM test, the standing ankle dorsiflexion screen (SADS). STUDY DESIGN: Reliability and validity study. METHODS: Thirty-seven healthy subjects participated in the study. Two raters measured closed-chain ankle DF range of motion (ROM) using a modified lunge position with an electronic inclinometer. Four raters measured ankle DF using the SADS. Reliability was calculated using intraclass correlation coefficients (ICC) and kappa coefficients for the raters using an electronic inclinometer and the SADS scale, respectively. An independent t-test compared the SADS categories of "behind" and "beyond" to the modified lunge test ROM (p<0.05). RESULTS: Excellent ICC values (0.95 [95% CI (0.92,0.97)]) and high kappa values were observed (0.61-0.81), with high percent agreement (86-94%). There was a significant difference in ankle DF ROM between the nominally scored "behind" and "beyond" categories, regardless of rater or trial analyzed (behind: 41.3° ± 4.7°; beyond: 51.8°± SD 6.1°, p <0.001). CONCLUSIONS: The SADS was observed to have excellent interrater reliability and high discriminant validity. Furthermore, there was a distinct closed chain ankle DF ROM difference between the "behind" and "beyond" SADS nominal scores. CLINICAL RELEVANCE: The SADS can be used as a quick and efficient closed chain ankle DF ROM screen. LEVEL OF EVIDENCE: 2b.

10.
Issues Ment Health Nurs ; 41(7): 568-573, 2020 Jul.
Article in English | MEDLINE | ID: mdl-32243213

ABSTRACT

Mental illness is a complex personal and social problem. In the African American community, cultural and ethnic stigma concerning mental illness often discourages this population from seeking the help they need. African Americans are more likely to rely on religious coping strategies such as prayer and/or informal trusted community social supports such as a senior pastor, members of a ministerial team who provide pastoral care in their churches, family members, and a limited number of friends. Implementation of a unique church-based initiative for depression/suicidality screening and stigma reduction, and collaborative efforts with community mental health providers, are promising steps toward optimizing diagnosis, treatment, follow-up for depression in African American persons in faith-based organizations. This project attempted to elaborate on and clarify the link between stigma, such as beliefs related to mental illness, and how education could influence and improve pastoral care by ministerial leaders for mental health issues in their congregants.


Subject(s)
Black or African American/psychology , Depressive Disorder, Major/therapy , Faith-Based Organizations , Pastoral Care/education , Quality Improvement , Adaptation, Psychological , Clergy/education , Ethnicity/psychology , Female , Health Knowledge, Attitudes, Practice , Humans , Male , Religion , Social Stigma , Suicide Prevention
11.
Int J Sports Phys Ther ; 15(1): 114-125, 2020 Feb.
Article in English | MEDLINE | ID: mdl-32089963

ABSTRACT

INTRODUCTION: Dysfunctional breathing (DB) is common (60-80%) in adults. Individuals with DB may have decreased pain thresholds, impaired motor control and balance, and movement dysfunction. These impairments likely adversely affect performance. Research has demonstrated that DB is multi-dimensional and includes biochemical, biomechanical, and psychophysiological categories. PURPOSE: The purpose of this study was to test the impact of breathing exercises in an otherwise healthy population of individuals diagnosed with at least one category of DB. It was hypothesized that the exercise program would normalize at least one category of DB. METHODS: An experimental group with DB was recruited, then the control group was matched for gender, age, BMI and activity. Baseline breathing metrics were obtained for each category of breathing dysfunction: capnography for biochemical (ETCO2 of < 35mmHg at rest = DB), HI-LO for biomechanical (upper chest or paradoxical patterns = DB), and Self-Evaluation of Breathing Questionnaire (SEBQ ≥ 25 = DB) and Nijmegen Questionnaire ( ≥ 22 = DB) for psychophysiological. The experimental group performed a four-week progression of home breathing exercises, once daily and the control group continued normal activities (no interventions). Re-testing of all outcome measures was performed after four weeks. RESULTS: Thirty-five individuals comprised the participant sample (16 experimental, 19 control, mean age 26.0 years, mean BMI of 24.3). There were no statistically significant differences between groups at baseline. Eighty-one percent of subjects in the experimental group improved in at least one category compared to 21% of subjects in the control group. Seventy-eight percent of subjects with biomechanical category of DB in the experimental group normalized this dysfunction, while none normalized in the control group, which was statistically significantly different. Twenty-seven percent of subjects with biochemical DB in the experimental group normalized, while only 25% in the control group which was not statistically different. There were only two subjects in each group with the psychophysiological category, therefore no analysis was performed. CONCLUSION: Home exercises were effective in reversing the biomechanical category of DB in 78% of young, otherwise healthy adults versus no exercise. However, the exercises did not affect the biochemical category of DB. Performing a set of home exercises may be an effective option for fitness and rehabilitation providers to suggest for clients to normalize biomechanical breathing dysfunction. LEVEL OF EVIDENCE: 2b.

12.
J Am Chem Soc ; 141(44): 17867-17874, 2019 11 06.
Article in English | MEDLINE | ID: mdl-31609114

ABSTRACT

Here we report the first series of in-plane thorium(IV), uranium(IV), and neptunium(IV) expanded porphyrin complexes. These actinide (An) complexes were synthesized using a hexa-aza porphyrin analogue, termed dipyriamethyrin, and the nonaqueous An(IV) precursors, ThCl4(DME)2, UCl4, and NpCl4(DME)2. The molecular and electronic structures of the ligand, each An(IV) complex, and a corresponding uranyl(VI) complex were characterized using nuclear magnetic resonance (NMR) and UV-vis spectroscopies as well as single-crystal X-ray diffraction analysis. Computational analyses of these complexes, coupled to their structural features, provide support for the conclusion that a greater degree of covalency in the ligand-cation orbital interactions arises as the early actinide series is traversed from Th(IV) to U(IV) and Np(IV). The axial ligands in the present An(IV) complexes proved labile, allowing for the electronic features of these complexes to be further modified.

13.
Angew Chem Int Ed Engl ; 57(49): 16136-16140, 2018 Dec 03.
Article in English | MEDLINE | ID: mdl-30328669

ABSTRACT

We report the synthesis, characterization, and electronic structure studies of a series of thorium(IV) and uranium(IV) bis-tetramethyltetraazaannulene complexes. These sandwich complexes show remarkable stability towards air and moisture, even at elevated temperatures. Electrochemical studies show the uranium complex to be stable in three different oxidation states; isolation of the oxidized species reveals a rare case of a non-innocent tetramethyltetraazaannulene (TMTAA) ligand.

14.
Dalton Trans ; 46(40): 13768-13782, 2017 Oct 17.
Article in English | MEDLINE | ID: mdl-28959804

ABSTRACT

We report the synthesis, characterization, and preliminary reactivity of new heteroleptic thorium and uranium complexes supported by the macrocyclic TMTAA ligand (TMTAA = Tetramethyl-tetra-aza-annulene). The dihalide complexes Th(TMTAA)Cl2(THF)2 (1), [UCl2(TMTAA)]2 (2) and U(TMTAA)I2 (3) are further functionalized to the Cp* derivatives ThCp*(TMTAA)Cl (4), UCp*(TMTAA)Cl (5) and UCp*(TMTAA)I (6) (Cp* = pentamethylcyclopentadienide). Compounds 4-6 are also obtained through a one-pot reaction from standard thorium(iv) and uranium(iv) starting materials, Li2TMTAA and KCp*. Complexes 1-6 function as valuable starting materials for salt metathesis chemistry. Treatment of precursors 4 or 5 with trimethylsilylmethyllithium (LiCH2TMS) results in the new actinide TMTAA alkyl complexes ThCp*(TMTAA)(CH2TMS) (7) and UCp*(TMTAA)(CH2TMTS) (8), respectively. The TMTAA-derived alkyl complexes (7 and 8) show unexpected stability and are stable for several weeks at room temperature in solution and in the solid-state. Additionally, double substitution of the halide ligands in 1-3 shows a strong dependence on the nucleophile used. While weaker nucleophiles, such as amides, and more sterically demanding nucleophiles, such as Cp (Cp = cyclopenadienide), favour the formation of bis-TMTAA "sandwich" complexes [An(TMTAA)2] (An = Th (9) and An = U (10)), the use of oxygen-functionalized ligands like the ODipp anion (Dipp = diisopropylphenyl) results in the formation of the doubly substituted species Th(ODipp)2TMTAA (11) and U(ODipp)2TMTAA (12). We also describe the divergent reactivity of the TMTAA ligand towards uranium(iii). Unlike the syntheses of actinide(iv) TMTAA complexes, the synthesis of a uranium(iii) TMTAA was not successful and only uranium(iv) species could be obtained.

15.
J Am Chem Soc ; 139(37): 12935-12938, 2017 09 20.
Article in English | MEDLINE | ID: mdl-28892619

ABSTRACT

The bis(NHC)borate-supported thorium-bis(mesitylphosphido) complex (1) undergoes reversible intramolecular C-H bond activation enabling the catalytic hydrophosphination of unactivated internal alkynes. Catalytic and stoichiometric experiments support a mechanism involving reactive Th-NHC metallacycle intermediates (Int and 2).

16.
Dalton Trans ; 46(35): 11615-11625, 2017 Sep 12.
Article in English | MEDLINE | ID: mdl-28831470

ABSTRACT

We report the coordination chemistry of the tripodal tris[2-amido(2-pyridyl)ethyl]amine ligand, L, with thorium(iv) and uranium(iv). Using a salt-metathesis strategy from the potassium salt of this ligand, K3L, new actinide complexes were isolated, namely the dimeric thorium complex [ThCl(L)]2 (1) and the monomeric uranium complex UI(THF)(L) (2); under different crystallisation conditions, the dimeric uranium complex is also isolated, [UI(L)]2 (2-dimer). With the aim of studying electronic phenomena such as magnetic exchange between two actinide ions, we have synthesised the first examples of dinuclear, quinoid-bridged actinide complexes from dianionic 2,5-bis[2,6-(diisopropyl)anilide]-1,4-benzoquinone (QDipp) and 2,5-bis[2-(methoxy)anilide]-1,4-benzoquinone (QOMe) ligands. The resulting complexes are [Th(L)]2QDipp (3), [Th(THF)(L)]2QOMe (5) and [U(L)]2QOMe (6). The targeted [U(L)]2QDipp complex (4) could not be isolated. All isolated complexes have been characterised by spectroscopic methods and X-ray crystallography. The uranium(iv) complexes 2-dimer and 6 have been studied by SQUID magnetometry but indicate that there is negligible magnetic exchange between the two uranium(iv) ions. The reduced form of 6, [K(18-c-6)][6-] is unstable and highly sensitive, but X-ray crystallography indicates that it is a novel UIVUIV complex bridged by a quinoid-radical.

17.
J Am Chem Soc ; 139(17): 6261-6269, 2017 05 03.
Article in English | MEDLINE | ID: mdl-28430420

ABSTRACT

A new thorium monoalkyl complex, Th(CH2SiMe3)(L3) (L = MeC(NiPr)2) (2), undergoes insertion of chalcogen atoms resulting in a series of thorium chalcogenolate complexes, Th(ECH2SiMe3)(L3) (E = S, SS, Se, Te; 5-8). Complex 6 represents the first alkyl disulfide thorium species and illustrates the ability of 2 to undergo controllable, stoichiometric atom insertion. All complexes have been characterized by 1H and 13C NMR spectroscopy, FTIR, EA, and melting point, and in the case of 1, 2, and 4-8, X-ray crystallography. Insertion was achieved by balancing the thermodynamic driving force of chalcogenolate formation versus the BDE of the pnictogen-chalcogen bond in the transfer reagent. Utilizing Me3NO as an oxygen atom transfer reagent led to C-H activation and SiMe4 extrusion rather than oxygen atom insertion, resulting in the alkoxide complex Th(OCH2NMe2)(L3) (4).


Subject(s)
Carbon/chemistry , Chalcogens/chemical synthesis , Organometallic Compounds/chemistry , Thorium Compounds/chemical synthesis , Chalcogens/chemistry , Crystallography, X-Ray , Models, Molecular , Molecular Conformation , Organometallic Compounds/chemical synthesis , Thermodynamics , Thorium Compounds/chemistry
18.
J Appl Meas ; 17(2): 166-184, 2016.
Article in English | MEDLINE | ID: mdl-28009582

ABSTRACT

In this paper we present the development and validation of a Mathematics Teaching Pedagogical and Discourse Beliefs Instrument (MTPDBI), a 20 item partial-credit survey designed and analyzed using Rasch measurement theory. Items on the MTPDBI address beliefs about the nature of mathematics, teaching and learning mathematics, and classroom discourse practices. A Rasch partial credit model (Masters, 1982) was estimated from the pilot study data. Results show that item separation reliability is .96 and person separation reliability is .71. Other analyses indicate the instrument is a viable measure of secondary teachers' beliefs about reform-oriented mathematics teaching and learning. This instrument is proposed as a useful measure of teacher beliefs for those working with pre-service and in-service teacher development.


Subject(s)
Mathematics/education , Psychometrics/methods , School Teachers/psychology , School Teachers/statistics & numerical data , Surveys and Questionnaires , Teaching/statistics & numerical data , Culture , Curriculum , Data Interpretation, Statistical , Reproducibility of Results , Sensitivity and Specificity , Teaching/psychology
19.
Angew Chem Int Ed Engl ; 55(44): 13789-13792, 2016 10 24.
Article in English | MEDLINE | ID: mdl-27699947

ABSTRACT

Actinide complexes demonstrate unparalleled reactivity towards small molecules. However, utilizing these powerful transformations in a predictable and deliberate manner remains challenging. Therefore, developing actinide systems that not only perform noteworthy chemistry but also demonstrate controllable reactivity is a key goal. We describe a bis(NHC)borate thorium-bpy complex (1) that is capable of reductively cleaving the R-NC bond in a series of organic isocyanides. In contrast to most actinide-mediated bond activations, the dealkylation event mediated by 1 is remarkably general and yields very well-defined products that assist in mechanistic elucidation. Synthesis of the rearranged but-3-enyl product from the reaction of 1 and cyclopropylmethyl isocyanide supports the notion of a radical-based mechanism.


Subject(s)
2,2'-Dipyridyl/chemistry , Heterocyclic Compounds/chemistry , Methane/analogs & derivatives , Organometallic Compounds/chemistry , Thorium/chemistry , 2,2'-Dipyridyl/analogs & derivatives , Carbon/chemistry , Crystallography, X-Ray , Methane/chemistry , Models, Molecular , Molecular Structure , Nitrogen/chemistry , Organometallic Compounds/chemical synthesis
20.
Dalton Trans ; 44(4): 1914-23, 2015 Jan 28.
Article in English | MEDLINE | ID: mdl-25490699

ABSTRACT

This work describes several synthetic approaches to append organic functional groups to gold and silver N-heterocyclic carbene (NHC) complexes suitable for applications in biomolecule conjugation. Carboxylate appended NHC ligands (3) lead to unstable Au(I) complexes that convert into bis-NHC species (4). A benzyl protected carboxylate NHC-Au(I) complex 2 was synthesized but deprotection to produce the carboxylic acid functionality could not be achieved. A small library of new alkyne functionalized NHC proligands were synthesized and used for subsequent silver and gold metalation reactions. The alkyne appended NHC gold complex 13 readily reacts with benzyl azide in a copper catalyzed azide-alkyne cycloaddition reaction to form the triazole appended NHC gold complex 14. Cell cytotoxicity studies were performed on DLD-1 (colorectal adenocarcinoma), Hep-G2 (hepatocellular carcinoma), MCF-7 (breast adenocarcinoma), CCRF-CEM (human T-Cell leukemia), and HEK (human embryonic kidney). Complete spectroscopic characterization of the ligands and complexes was achieved using (1)H and (13)C NMR, gHMBC, ESI-MS, and combustion analysis.


Subject(s)
Gold/chemistry , Heterocyclic Compounds/chemistry , Methane/analogs & derivatives , Organometallic Compounds/chemistry , Silver/chemistry , Cell Line , Cell Line, Tumor , Cell Survival/drug effects , Gold/pharmacology , Heterocyclic Compounds/pharmacology , Humans , Magnetic Resonance Spectroscopy , Methane/chemistry , Methane/pharmacology , Organometallic Compounds/pharmacology , Silver/pharmacology , Spectrometry, Mass, Electrospray Ionization
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