Cand1 Promotes Assembly of New SCF Complexes through Dynamic Exchange of F Box Proteins

Pierce, Nathan W.,Lee, J.,Liu, X.,Sweredoski, Michael J.,Graham, Robert L.J.,Larimore, Elizabeth A.,Rome, M.,Zheng, N.,Clurman, Bruce E.,Hess, S.,Shan, S.o.,Deshaies, Raymond J. Cell Press ; MIT Press 2013 Cell Vol.153 No.1

The modular SCF (Skp1, cullin, and F box) ubiquitin ligases feature a large family of F box protein substrate receptors that enable recognition of diverse targets. However, how the repertoire of SCF complexes is sustained remains unclear. Real-time measurements of formation and disassembly indicate that SCF<SUP>Fbxw7</SUP> is extraordinarily stable, but, in the Nedd8-deconjugated state, the cullin-binding protein Cand1 augments its dissociation by one-million-fold. Binding and ubiquitylation assays show that Cand1 is a protein exchange factor that accelerates the rate at which Cul1-Rbx1 equilibrates with multiple F box protein-Skp1 modules. Depletion of Cand1 from cells impedes recruitment of new F box proteins to pre-existing Cul1 and profoundly alters the cellular landscape of SCF complexes. We suggest that catalyzed protein exchange may be a general feature of dynamic macromolecular machines and propose a hypothesis for how substrates, Nedd8, and Cand1 collaborate to regulate the cellular repertoire of SCF complexes.

Human Somatic Cell Nuclear Transfer Using Adult Cells

Chung, Y.,Eum, J.,Lee, J.,Shim, S.,Sepilian, V.,Hong, S.,Lee, Y.,Treff, Nathan R.,Choi, Y.,Kimbrel, Erin A.,Dittman, Ralph E.,Lanza, R.,Lee, D. Cell Press 2014 Cell stem cell Vol.14 No.6

Derivation of patient-specific human pluripotent stem cells via somatic cell nuclear transfer (SCNT) has the potential for applications in a range of therapeutic contexts. However, successful SCNT with human cells has proved challenging to achieve, and thus far has only been reported with fetal or infant somatic cells. In this study, we describe the application of a recently developed methodology for the generation of human ESCs via SCNT using dermal fibroblasts from 35- and 75-year-old males. Our study therefore demonstrates the applicability of SCNT for adult human cells and supports further investigation of SCNT as a strategy for regenerative medicine.

Effects of TiCl₄ Treatment of Nanoporous TiO₂ Films on Morphology, Light Harvesting, and Charge-Carrier Dynamics in Dye-Sensitized Solar Cells

Lee, Sang-Wha,Ahn, Kwang-Soon,Zhu, Kai,Neale, Nathan R.,Frank, Arthur J. American Chemical Society 2012 The Journal of Physical Chemistry Part C Vol.116 No.40

<P>We report on the effects of treating TiO<SUB>2</SUB> nanocrystalline films with different concentrations of TiCl<SUB>4</SUB> (5–500 mM) on the film morphology, charge-carrier dynamics, and performance of dye-sensitized solar cells. Transport and recombination in the TiCl<SUB>4</SUB>-treated films were studied by frequency-resolved modulated photocurrent/photovoltage spectroscopies. These studies showed that, at a low TiCl<SUB>4</SUB> concentration (5 mM), the electron diffusion coefficient in the annealed film increased. At intermediate TiCl<SUB>4</SUB> concentrations (15–50 mM), the surface area of the films increased, resulting in an increase of light harvesting and overall power conversion efficiency. At a high TiCl<SUB>4</SUB> concentration (500 mM), light scattering in the film in the long wavelength region of the visible spectrum was enhanced, but the averaged pore size of the film became narrower, resulting in slower transport and loss of cell performance.</P><P><B>Graphic Abstract</B> <IMG SRC='http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/jpccck/2012/jpccck.2012.116.issue-40/jp3079887/production/images/medium/jp-2012-079887_0007.gif'></P>

The effects of news consumption via social media and news information overload on perceptions of journalistic norms and practices

Lee, Sun Kyong,Lindsey, Nathan J.,Kim, Kyun Soo Elsevier 2017 Computers in Human Behavior Vol.75 No.-

<P><B>Abstract</B></P> <P>Given the widespread adoption of social media for sharing and accessing news, as well as the possibility of news consumers' direct interactions with journalists through social media, this study analyzed the relationships among news access via social media (NASM), perceived news information overload (NIO), news consumption, and perceptions of journalistic norms and practices. The results indicated that NIO moderated the relationships between NASM and selective exposure and between NASM and willingness to pay for quality news. Regarding journalistic norms and practices, participants valued the speed of journalism when they frequently accessed news on social media more so than traditional journalistic norms. Finally, there were statistically significant interactions between NIO and two types of news consumption behaviors (i.e., selective exposure and news avoidance) concerning participants' perceptions of news quality.</P> <P><B>Highlights</B></P> <P> <UL> <LI> The impact of social media news use on selective exposure is conditioned by news information overload. </LI> <LI> The impact of social media news use on willingness to pay is conditioned by news information overload. </LI> <LI> Frequent social media news use is associated with speed of journalism. </LI> <LI> Frequent social media news use is related to disagreement with traditional journalistic norms. </LI> <LI> News consumptions interact with news information overload and influence perceived news quality. </LI> </UL> </P>

Chronic Cerebrospinal Venous Insufficiency in Multiple Sclerosis: A Failed Concept

Nathan Kugler,Parag J. Patel,cheong Jun Lee 대한혈관외과학회 2015 Vascular Specialist International Vol.31 No.1

In 2009 Paolo Zamboni et al. implicated that chronic cerebral venous congestion lead to the development of multiple sclerosis. In this review, we examined the role of chronic cerbrospinal venous insufficiency in multiple sclerosis and the proposed therapy entailing venous angioplasty and stenting of extracranial veins with available evidence to date.

Freehand Juxtapedicular Screws Placed in the Apical Concavity of Adult Idiopathic Scoliosis Patients: Technique, Computed Tomography Confirmation, and Radiographic Results

Alexander J. Schupper,James D. Lin,Joseph A. Osorio,Nathan J. Lee,Jeremy M Steinberger,Joseph M. Lombardi,Ronald A. Lehman,Lawrence G. Lenke 대한척추신경외과학회 2022 Neurospine Vol.19 No.4

Objective: The purpose of this study is to highlight our technique for freehand placement of juxtapedicular screws along with intraoperative computed tomography (CT) and radiographic results. Methods: Consecutive patients with adult idiopathic scoliosis undergoing primary surgery by the senior author were identified. All type D (absent/slit like channel) pedicles were identified on preoperative CT. Three-dimensional visualization software was used to measure screw angulation and purchase. Radiographs were measured by a fellowship trained spine surgeon. The freehand technique was used to place all screws in a juxtapedicular fashion without any fluoroscopic, radiographic, navigational or robotic assistance. Results: Seventy-three juxtapedicular screws were analyzed. The most common level was T7 (9 screws) on the left and T5 (12 screws) on the right. The average medial angulation was 20.7° (range, 7.1°–36.3°), lateral vertebral body purchase was 13.4 mm (range, 0–28.9 mm), and medial vertebral body purchase was 21.1 mm (range, 8.9–31.8 mm). More than half (53.4%) of the screws had bicortical purchase. Two screws were lateral on CT scan, defined by the screw axis lateral to the lateral vertebral body cortex. No screws were medial. There was a difference in medial angulation between screws with (n = 58) and without (n = 15) lateral body purchase (22.0 ± 4.9 vs. 15.5 ± 4.5, p < 0.001). Three of 73 screws were repositioned after intraoperative CT. There were no neurovascular complications. The mean coronal cobb corrections for main thoracic and lumbar curves were 83.0% and 80.5%, respectively, at an average of 17.5 months postoperative. Conclusion: Freehand juxtapedicular screw placement is a safe technique for type D pedicles in adult idiopathic scoliosis patients.

The Posterior Cranial Vertical Line: A Novel Radiographic Marker for Classifying Global Sagittal Alignment

Paul J. Park,Fthimnir M. Hassan,Xavier E. Ferrer,Cole Morrissette,Nathan J. Lee,Meghan Cerpa,Zeeshan M. Sardar,Michael P. Kelly,Stephane Bourret,Kazuhiro Hasegawa,Hee-Kit Wong,Gabriel Liu,Hwee Weng De 대한척추신경외과학회 2023 Neurospine Vol.20 No.3

Objective: To define a novel radiographic measurement, the posterior cranial vertical line (PCVL), in an asymptomatic adult population to better understand global sagittal alignment. Methods: We performed a multicenter retrospective review of prospectively collected radiographic data on asymptomatic volunteers aged 20–79. The PCVL is a vertical plumb line drawn from the posterior-most aspect of the occiput. The horizontal distances of the PCVL to the thoracic apex (TA), posterior sagittal vertical line (PSVL, posterosuperior endplate of S1), femoral head center, and tibial plafond were measured. Classification was either grade 1 (PCVL posterior to TA and PSVL), grade 2 (PCVL anterior to TA and posterior to PSVL), or grade 3 (PCVL anterior to TA and PSVL). Results: Three hundred thirty-four asymptomatic patients were evaluated with a mean age of 41 years. Eighty-three percent of subjects were PCVL grade 1, 15% were grade 2, and 3% were grade 3. Increasing PCVL grade was associated with increased age (p < 0.001), C7–S1 sagittal vertical axis (SVA) (p < 0.001), C2–7 SVA (p < 0.001). Additionally, it was associated with decreased SS (p = 0.045), increased PT (p < 0.001), and increased knee flexion (p < 0.001). Conclusion: The PCVL is a radiographic marker of global sagittal alignment that is simple to implement and interpret. Increasing PCVL grade was significantly associated with expected changes and compensatory mechanisms in the aging population. Most importantly, it incorporates cervical alignment parameters such as C2–7 SVA. The PCVL defines global sagittal alignment in adult volunteers and naturally distributes into 3 grades, with only 3% being grade 3 where the PCVL lies anterior to the TA and PSVL.

Circumferential Operations of the Cervical Spine

Andrei Fernandes Joaquim,Nathan J. Lee,K. Daniel Riew 대한척추신경외과학회 2021 Neurospine Vol.18 No.1

Generally, a combined anterior and posterior cervical approach is associated with significant morbidity since it requires an extended operative time, greater intraoperative blood loss, and both anterior- and posterior-related surgical complications. However, there are some instances where a circumferential cervical fusion can be advantageous. Our objective is to discuss the indications for circumferential cervical spine procedures. A narrative review of the literature was performed. We include the indications for circumferential cervical approaches of the senior author (KDR). Indications for circumferential approaches include: (1) high-risk patients for pseudoarthrosis, (2) cervical deformity (e.g., degenerative, posttraumatic, cervicothoracic kyphosis), (3) cervical spine metastases (especially those with multilevel involvement), (4) cervical spine infection, (5) unstable cervical trauma, (6) movement disorders and cerebral palsy, (7) Multiply operated patient (especially postlaminectomy kyphosis and patients with massive ossification of the posterior longitudinal ligament), and when (8) early fusion is desirable. Circumferential procedures may be useful in many different cervical spine conditions requiring surgery. Despite its advantages, particularly with reducing the risk for pseudarthrosis, the benefits of a combined approach must be weighed against the risks associated with a dual approach. With appropriate preoperative planning, intraoperative decision-making, and surgical techniques, excellent clinical outcomes can be achieved.

Revision Surgeries at the Index Level After Cervical Disc Arthroplasty – A Systematic Review

Andrei Fernandes Joaquim,Nathan J. Lee,K. Daniel Riew 대한척추신경외과학회 2021 Neurospine Vol.18 No.1

Objective: To perform a systematic literature review on revision surgeries at the index level after cervical disc arthroplasty (CDA) failure. Methods: A systematic literature review was performed according to the PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses) guidelines. Prospective studies on patients who required a secondary surgery after CDA failure were included for analysis. The minimum follow-up for these studies was 5 years. Results: Out of 864 studies in the original search group, a total of 20 studies were included. From a total of 4,087 patients, 161 patients required a reoperation at the index level. A total of 170 surgeries were performed, as some patients required multiple surgeries. The most common secondary procedures were anterior cervical discectomy and fusion (ACDF) (68%, N=61) and posterior cervical fusion (15.5%, N=14), followed by other reoperation (13.3%, N=12). The associated outcomes for those who required a revision surgery were rarely mentioned in the included literature. Conclusion: The long-term revision rate at the index level of failed CDA surgery was 3.9%, with a minimum 5-year follow-up. ACDF was the most commonly performed procedure to salvage a failed CDA. Some patients who required a new surgery after CDA failure may require a more extensive salvage procedure and even subsequent surgeries.

Involvement of reactive oxygen species in cocaine-taking behaviors in rats.

Jang, Eun Young,Ryu, Yeon-Hee,Lee, Bong Hyo,Chang, Su-Chan,Yeo, Mi Jin,Kim, Sang Hyun,Folsom, Ryan J,Schilaty, Nathan D,Kim, Kwang Joong,Yang, Chae Ha,Steffensen, Scott C,Kim, Hee Young Carfax 2015 Addiction Biology Vol.20 No.4

<P>Reactive oxygen species (ROS) have been implicated in the development of behavioral sensitization following repeated cocaine exposure. We hypothesized that increased ROS following cocaine exposure would act as signaling molecules in the mesolimbic dopamine (DA) system, which might play an important role in mediating the reinforcing effects of cocaine. The aim of this study was to evaluate cocaine enhancement of brain metabolic activity and the effects of ROS scavengers on cocaine self-administration behavior, cocaine-induced ROS production in the nucleus accumbens (NAc) and cocaine enhancement of DA release in the NAc. Metabolic neural activity monitored by temperature and oxidative stress were increased in NAc following cocaine exposure. Systemic administration of the ROS scavenger N-tert-butyl-α-phenylnitrone (PBN) or 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPOL), either pre- or post-treatment, significantly decreased cocaine self-administration without affecting food intake. Infusion of TEMPOL into the NAc inhibited cocaine self-administration. Increased oxidative stress was found mainly on neurons, but not astrocytes, microglia or oligodendrocytes, in NAc of rats self-administering cocaine. TEMPOL significantly attenuated cocaine-induced enhancement of DA release in the NAc, compared to saline controls. TEMPOL had no effect on the enhancement of DA release produced by the DA transporter inhibitor GBR12909. Taken together, these findings suggest that enhancement of ROS production in NAc neurons contributes to the reinforcing effect of cocaine.</P>