Learning gene networks under SNP perturbation using SNP and allele-specific expression data.

Allele-specific expression quantification from RNA-seq reads provides opportunities to study the control of gene regulatory networks by cis-acting and trans-acting genetic variants. Many existing methods performed a single-gene and single-SNP association analysis to identify expression quantitative trait loci (eQTLs), and placed the eQTLs against known gene networks for functional interpretation. Instead, we view eQTL data as a capture of the effects of perturbation of gene regulatory system by a large number of genetic variants and reconstruct a gene network perturbed by eQTLs. We introduce a statistical framework called CiTruss for simultaneously learning a gene network and cis-acting and trans-acting eQTLs that perturb this network, given population allele-specific expression and SNP data. CiTruss uses a multi-level conditional Gaussian graphical model to model trans-acting eQTLs perturbing the expression of both alleles in gene network at the top level and cis-acting eQTLs perturbing the expression of each allele at the bottom level. We derive a transformation of this model that allows efficient learning for large-scale human data. Our analysis of the GTEx and LG×SM advanced intercross line mouse data for multiple tissue types with CiTruss provides new insights into genetics of gene regulation. CiTruss revealed that gene networks consist of local subnetworks over proximally located genes and global subnetworks over genes scattered across genome, and that several aspects of gene regulation by eQTLs such as the impact of genetic diversity, pleiotropy, tissue-specific gene regulation, and local and long-range linkage disequilibrium among eQTLs can be explained through these local and global subnetworks.

Movement-Related Potentials Associated with Motor Timing Errors as Determined by Internally Cued Movement Onset.

OBJECTIVE: Accurate motor timing is critical for efficient motor control of behaviors; however, the effect of motor timing abilities on movement-related neural activities has rarely been investigated. The current study aimed to examine the electrophysiological correlates of motor timing errors. METHODS: Twenty-two healthy volunteers performed motor timing tasks while their electroencephalographic and electromyographic (EMG) activities were simultaneously recorded. The average of intervals between consecutive EMG onsets was calculated separately for each subject. Motor timing error was calculated as an absolute discrepancy value between the subjects' produced and given time interval. A movement-related potential (MRP) analysis was conducted using readings from Cz electrode. RESULTS: Motor timing errors and MRPs were significantly correlated. Our principal finding was that only Bereitschaftpotential (BP) and motor potential (MP), not movement monitoring potential, were significantly attenuated in individuals with motor timing errors. Motor timing error had a significant effect on the amplitude of the late BP and MP. CONCLUSION: The findings provide electrophysiological evidence that motor timing errors correlate with the neural processes involved in the generation of self-initiated voluntary movement. Alterations in MRPs reflect central motor control processes and may be indicative of motor timing deficits.

The Impact of Preoperative α-Adrenergic Antagonists on Ureteral Access Sheath Insertion Force and the Upper Limit of Force Required to Avoid Ureteral Mucosal Injury: A Randomized Controlled Study.

PURPOSE: Excessive bulking force during primary access of the ureteral access sheath may induce ureteral injury. We investigated the efficacy of preoperative α-blockade to reduce ureteral access sheath insertion force and determine the upper limit required to avoid ureteral injury. MATERIALS AND METHODS: In this randomized controlled trial 135 patients from a single institution who had ureteropelvic junction or renal pelvis stones and were scheduled to undergo retrograde intrarenal surgery were prospectively enrolled from December 2015 to January 2017. Of the patients 41 and 42 were randomly assigned to the control and experimental groups, respectively. The experimental group received α-blockade preoperatively. The 21 patients who were pre-stented were assessed separately. We developed a homemade device to measure maximal ureteral access sheath insertion force. RESULTS: Our ureteral access sheath insertion force measurement device showed excellent reproducibility. Higher insertion velocity resulted in greater maximal sheath insertion force. Maximal insertion force in the α-blockade group was significantly lower than in the control group at the ureterovesical junction (p = 0.008) and the proximal ureter (p = 0.036). Maximal insertion force in the α-blockade group was comparable to that in pre-stented patients. Female patients and patients 70 years old or older showed a lower maximal ureteral access sheath insertion force than their counterparts. The rate of grade 2 or greater ureteral injury was lower in the α-blockade group than in controls (p = 0.038). No injury occurred in any case in which ureteral access sheath insertion force did not exceed 600 G. CONCLUSIONS: Preoperative α-blockade and slow sheath placement may reduce maximal ureteral access sheath insertion force. If the force exceeds 600 G, a smaller diameter sheath may be an alternative. Alternatively the procedure can be terminated and followed later by pre-stented retrograde intrarenal surgery.

Preparation and characterization of nano-sized hydroxyapatite/alginate/chitosan composite scaffolds for bone tissue engineering.

The aim of this study was to develop chitosan composite scaffolds with high strength and controlled pore structures by homogenously dispersed nano-sized hydroxyapatite (nano-HAp) powders. In the fabrication of composite scaffolds, nano-HAp powders distributed in an alginate (AG) solution with a pH higher than 10 were mixed with a chitosan (CS) solution and then freeze dried. While the HAp content increased up to 70 wt.%, the compressive strength and the elastic modulus of the composite scaffolds significantly increased from 0.27 MPa and 4.42 MPa to 0.68 MPa and 13.35 MPa, respectively. Higher content of the HAp also helped develop more differentiation and mineralization of the MC3T3-E1 cells on the composite scaffolds. The uniform pore structure and the excellent mechanical properties of the HAp/CS composite scaffolds likely resulted from the use of the AG solution at pH 10 as a dispersant for the nano-HAp powders.

Vibronic structures and dynamics of the predissociating dimethyl sulfide and its isotopomers (CH3SCH3, CD3SCD3, CH3SCD3) at the conical intersection.

Conical intersection seam comprised of crossing surfaces of two lowest excited states of dimethyl sulfide (DMS) has been directly accessed by the one-photon excitation from the ground equilibrium state. Since the S-C bond rupture takes place promptly, the molecular structure on the excited state effectively belongs to C(S) symmetry. Namely, excited states of 1(1)B1 and 1(1)A2 in C(2)V become 1(1)A'' and 2(1)A'' states in C(S), respectively, and the optical transition from the ground equilibrium state to the dissociating molecule at the conical intersection seam is symmetry-allowed to facilitate the nonadiabatic transition on the 2(1)A'' state, leading eventually to the CH3S + CH3 products. The dynamic study of DMS, in this sense, gives the great opportunity to unravel the vibronic structure of the conical intersection seam by the conventional one-photon excitation method. In this work, utilizing the photofragment excitation (PHOFEX) spectroscopic method, the vibronic structures of DMS and its isotope analogs (CD3SCD3, CH3SCD3) at the conical intersection seam have been revealed, providing accurate lifetimes and detailed dynamics associated with individual vibronic transitions. The lifetime of the excited DMS is estimated to be ~100 fs, indicating that the dissociation is complete within one single oscillation in the conical intersection region. It is also found that the symmetric CSC stretching mode is strongly coupled to the reaction coordinate, as manifested by our experimental finding that the fragmentation yield of the S-CD3 bond is enhanced compared to that of the S-CH3 bond in the CH3SCD3 dissociation reaction only when the CSC symmetric stretching vibrational mode is excited at the conical intersection region. This work demonstrates that the better understanding of the excited state could make the bond-selective chemistry into reality.

Conical intersection seam and bound resonances embedded in continuum observed in the photodissociation of thioanisole-d3.

Herein, the multi-dimensional nature of the conical intersection seam has been experimentally revealed in the photodissociation reaction of thioanisole-d3 (C6H5SCD3) excited on S1, giving C6H5S·(à or X̃]) +·CD3 products. The translational energy distribution of the nascent·CD3 fragment, reflecting the relative yields of the C6H5S·(Ã) and C6H5S·(X̃) products, was measured at each S1 vibronic band using the velocity map ion imaging technique. Direct access of the reactant flux to the conical intersection seam leads to the increase of the nonadiabatic transition probability resulting in sharp resonances in the X̃/ÃC6H5S·product branching ratio at several distinct S1 vibronic bands. The nature of the S1 vibronic bands associated with such dynamic resonances was clarified by the mass-analyzed threshold ionization spectroscopy. The bound state embedded in continuum generated by the conical intersection is observed as a distinct dynamic resonance, revealing the nature of the nuclear motion responsible for the nonadiabatic coupling of two potential energy surfaces at the conical intersection. The multi-dimensional facets of the conical intersection seam in terms of its detailed structure and dynamic role are discussed with the aid of theoretical calculations.

Intravitreal triamcinolone acetonide injection at the time of pars plana vitrectomy for retained lens material.

PURPOSE: To report the experiences at our institute of pars plana vitrectomy (PPV) in combination with intravitreal triamcinolone acetonide (IVTA) injection in patients with retained lens material after cataract surgery. METHODS: The medical records of patients who underwent PPV between January 2005 and December 2006 after complicated cataract surgery in which lens material was dropped into the vitreous cavity were reviewed retrospectively. RESULTS: Five eyes of five patients were treated by vitrectomy and removal of the dislocated lens material and were administered an adjuvant intravitreal injection of 4 mg triamcinolone acetonide at the end of surgery. IVTA administration induced a rapid improvement in vision within six weeks postoperatively. Final visual acuity was 20/32 or better in all patients. Inflammatory cystoid macular edema (CME) that existed preoperatively was promptly improved after IVTA. Intraocular pressure increased transiently in one patient. No procedure-related complications were observed. CONCLUSIONS: PPV with additional IVTA was successfully performed in five eyes with retained lens material and resulted in a marked resolution of vitreous inflammation, an improvement in CME and rapid visual recovery. The authors recommend that IVTA administration should be investigated more thoroughly as an adjunct during the management of retained lens material.

Transthoracic echocardiography and carotid Doppler ultrasound for detection of cardiac and carotid artery disease in patients with acute retinal artery obstruction.

We reviewed the medical records of patients with acute retinal artery obstruction (RAO) and evaluated the importance of transthoracic echocardiography (TTE) and carotid Doppler ultrasound in determining causes of cardiac and carotid artery origin in RAO. A retrospective case study conducted in the Department of Ophthalmology, Inha University Hospital, Korea comprised 26 patients presenting with acute RAO who underwent systemic evaluation, TTE and carotid Doppler ultrasound between June 1, 1997 and December 31, 2003. Among these 26 patients, abnormal cardiac findings were detected in 12 (46%) and abnormal carotid findings in 4 (15%). Furthermore, other risk factors for RAO were found in 2 (8%) and stroke broke out within 7 months after experiencing RAO in 4 (15%) of the 26 patients. In patients with acute RAO, TTE and carotid Doppler ultrasound play an important role in pinpointing the origins of retinal emboli. It is thought that TTE and carotid Doppler ultrasound may be essential examinations for determining the underlying cause, planning treatment strategies, and preventing stroke and death.