Characterization of a Novel Model of Lumbar Ligamentum Flavum Hypertrophy in Bipedal Standing Mice.

OBJECTIVE: To explore the main causes of hypertrophied ligamentum flavum (HLF) and the possibility of using bipedal standing mouse model to simulate the pathological changes in human HLF. METHODS: Thirty-two 8-week-old C57BL/6 male mice were randomly assigned to the experimental group (n = 16) and control group (n = 16). In the experimental group, mice were induced to adopt a bipedal standing posture by their hydrophobia. The experimental mice were maintained bipedal standing for 8 h a day with an interval of 2 h to consume food and water. The control mice were placed in a similar environment without bipedal standing. Eight 18-month-old C57BL/6 male mice were compared to evaluate the LF degeneration due to aging factor. Three-dimensional (3D) reconstruction and finite element models were carried out to analyze the stress and strain distribution of the mouse LF in sprawling and bipedal standing postures. Hematoxylin and Eosin (HE), Verhoeff-Van Gieson (VVG), and immunohistochemistry (IHC) staining were used to evaluate the LF degeneration of mice and humans. RT-qPCR and immunofluorescence analysis were used to evaluate the expressions of fibrosis-related factors and inflammatory cytokines of COL1A1, COL3A1, α-SMA, MMP2, IL-1ß, and COX-2. RESULTS: The von Mises stress (8.85 × 10-2 MPa) and maximum principal strain (6.64 × 10-1 ) in LF were increased 4944 and 7703 times, respectively, in bipedal standing mice. HE staining showed that the mouse LF area was greater in the bipedal standing 10-week-old group ([10.01 ± 2.93] × 104 µm2 ) than that in the control group ([3.76 ± 1.87] × 104 µm2 ) and 18-month-old aged group ([6.09 ± 2.70] × 104 µm2 ). VVG staining showed that the HLF of mice (3.23 ± 0.58) and humans (2.23 ± 0.31) had a similar loss of elastic fibers and an increase in collagen fibers. The cell density was higher during the process of HLF in mice (39.63 ± 4.81) and humans (23.25 ± 2.05). IHC staining showed that the number of α-SMA positive cells were significantly increased in HLF of mice (1.63 ± 0.74) and humans (3.50 ± 1.85). The expressions of inflammatory cytokines and fibrosis-related factors of COL1A1, COL3A1, α-SMA, MMP2, IL-1ß, and COX-2 were consistently higher in bipedal standing group than the control group. CONCLUSION: Our study suggests that 3D finite element models can help analyze the abnormal stress and strain distributions of LF in modeling mice. Mechanical stress is the main cause of hypertrophied ligamentum flavum compared to aging. The bipedal standing mice model can reflect the pathological characteristics of human HLF. The bipedal standing mice model can provide a standardized condition to elucidate the molecular mechanisms of mechanical stress-induced HLF in vivo.

Impurity-driven transitions in frustrated quantum Ising rings.

We study the quantum phase transition driven by a point impurity in a chain seamed with ring frustration. With strong coupling and light impurity, the system is in a topological extended-kink (TEK) phase, which exhibits gapless excitations in the bulk. With strong coupling and heavy impurity, the system is in a gapped kink bound state (KBS) phase. Two-point bulk and impurity correlations are defined to characterize the two phases. In the TEK phase, both the bulk and impurity correlations are long range and factorizable so that scaling functions can be parsed. The scaling functions relies on the distance scaled by the system's size. An impurity correlation length can be extracted from the impurity correlation. In the transition from TEK to KBS, the scaling function of the bulk correlation undergoes an abrupt steplike change. Meanwhile, the impurity correlation length decreases from a divergent value to a finite one. The ground state of the TEK phase retains a relatively high value of entanglement entropy due to the absence of symmetry breaking. However, spontaneous symmetry breaking occurs in the KBS phase, which induces antiferromagnetic order in the bulk and entangled spin configuration near the impurity.

Relationship between the location of ligamentum flavum hypertrophy and its stress in finite element analysis.

OBJECTIVE: To quantitatively describe the stress of the ligamentum flavum (LF) using the finite element method and to compare the stress at different parts of the healthy LF. METHODS: Based on the high resolution computed tomography imaging data of a healthy 22-year-old man, three-dimensional nonlinear L4-5 lumbar finite element model (FEM) representing intact condition was developed. The LF, as the object of the present research, was incorporated into the spinal model in the form of solid three-dimensional structure. The model's validity is verified by comparing its biomechanical indices, such as range of motion and axial compression pressure displacement, with published results under specific loading conditions. To authenticate the accuracy of the solid LF, the lamina attachments, the central cross-section, and other anatomy indicators were compared with figures in the published literature. After the average and maximum von Mises stress on the surface of LF under various working conditions were measured using ANSYS and AutoCAD software, the surface stress difference in the LF between the ventral and dorsal sides as well as the lateral and lamina parts were determined. RESULTS: The FEM predicted a similar tendency for biomechanical indices as shown in previous studies. The lamina attachments, the central cross-section, and the height as well as the width of the LF in the healthy FEM were in accordance with published results. In the healthy model, the average and maximum von Mises stress in the shallow layer of the LF were, respectively, 1.40, 2.28, 1.76, 1.48, 1.38 and 1.79, 2.41, 1.46, 1.42, 1.71 times that in the deep layer under a compressive preload of 500 N incorporated with flexion, extension, and lateral and rotational moments (10 Nm). The most conspicuous difference in surface stress was observed with the flexion motion, with a nearly 241% difference in the maximum stress and a 228% difference in the average stress compared to those in other states. As far as the whole dorsal side of the LF was concerned, the maximum surface stress was almost all concentrated in the dorsal neighboring facet joint portion. In addition, the maximum and average stress were, respectively, 77%, 72%, 15%, 11%, 71% and 153%, 39%, 54%, 200%, 212% higher in the lateral part than in the lamina part. CONCLUSION: Based on the predisposition of LF hypertrophy in the human spine and the stress distribution of this study, the positive correlation between LF hypertrophy and its stress was confirmed.

Rigorous proof for the nonlocal correlation function in the transverse Ising model with ring frustration.

An unusual correlation function was conjectured by Campostrini et al. [Phys. Rev. E 91, 042123 (2015)PLEEE81539-375510.1103/PhysRevE.91.042123] for the ground state of a transverse Ising chain with geometrical frustration. Later, we provided a rigorous proof for it and demonstrated its nonlocal nature based on an evaluation of a Toeplitz determinant in the thermodynamic limit [J. Stat. Mech. (2016) 11310210.1088/1742-5468/2016/11/113102]. In this paper, we further prove that all the low excited energy states forming the gapless kink phase share the same asymptotic correlation function with the ground state. As a consequence, the thermal correlation function almost remains constant at low temperatures if one assumes a canonical ensemble.

Locating a modifier gene of Ovum mutant through crosses between DDK and C57BL/6J inbred strains in mice.

A striking infertile phenotype has been discovered in the DDK strain of mouse. The DDK females are usually infertile when crossed with males of other inbred strains, whereas DDK males exhibit normal fertility in reciprocal crosses. This phenomenon is caused by mutation in the ovum (Om) locus on chromosome 11 and known as the DDK syndrome. Previously, some research groups reported that the embryonic mortality deviated from the semilethal rate in backcrosses between heterozygous (Om/+) females and males of other strains. This embryonic mortality exhibited an aggravated trend with increasing background genes of other strains. These results indicated that some modifier genes of Om were present in other strains. In the present study, a population of N22 (Om/+) females from the backcrosses between C57BL/6J (B6) and F1 (B6♀ × DDK♂) was used to map potential modifier genes of Om. Quantitative trait locus showed that a major locus, namely Amom1 (aggravate modifier gene of Om 1), was located at the middle part of chromosome 9 in mice. The Amom1 could increase the expressivity of Om gene, thereby aggravating embryonic lethality when heterozygous (Om/+) females mated with males of B6 strain. Further, the 1.5 LOD-drop analysis indicated that the confidence interval was between 37.54 and 44.46 cM, ~6.92 cM. Amom1 is the first modifier gene of Om in the B6 background.

Using positive-ion electrospray ionization mass spectrometry and H/D exchange study phosphoryl group transfer reactions involved in amino acid ester isopropyl phosphoramidates of Brefeldin A.

As mini-chemical models, amino acid ester isopropyl phosphoramidates of Brefeldin A (compounds 2a-2d) were synthesized and investigated by electrospray ionization tandem mass spectrometry in combination with H/D exchange. To further confirm the fragments's structures, off-line Fourier transform resonance tandem mass spectrometry (FT-ICR-MS/MS) was also performed. The fragmentation rules of compounds 2a-2d have been summarized and the plausible schemes for the fragmentation pathways were proposed. In this study, one dephosphorylated ion and two phosphorylated ions were observed in ESI-MS(2) spectra of [M+Na](+) ions for compounds 2a-2d. The possible mechanisms about phosphorylation and dephosphorylation were proposed and confirmed by H/D exchange. For the "dephosphorylation" rearrangement, a nitrogen atom was migrated from the phosphoryl group to the carbon atom of Brefeldin A's backbone with losing a molecule of C3H7PO3 (122 Da). For the "phosphorylation" rearrangement, an oxygen atom of one phosphoryl group attacked the sideward phosphorus atom to form a nine-member ring intermediate, then two steps of CH covalent bond cleavage with consecutive migration of hydrogen atom to lose a molecule of C16H20O2 (244 Da). The two proposed rearrangement mechanisms about phosphoryl group transfer might be valuable for the structure analysis of other analogs and provide insights into elucidating the dynamic process of the phosphorylation-dephosphorylation of proteins.

Cloning, expression and characterization of antimicrobial porcine ß defensin 1 in Escherichia coli.

Porcine ß defensin 1 (pBD1) is a cationic antimicrobial peptide with three pairs of disulfide bonds. When expressed in insect cells, two polypeptides of different length (pBD1(38) and pBD1(42)) accumulated, which differed by N-terminal truncation. However, only pBD1(42) was found in pigs. pBD1(42) had stronger antimicrobial activity than pBD1(38), and thus could be a good candidate as a bactericidal agent for pigs. In this study, pBD1(42) gene, obtained by RT-PCR using the tongue total RNA as a template, was cloned into pET30a expression vector and transformed into Escherichia coli BL21 (DE3) plysS. The recombinant pBD1(42) was expressed after induction by IPTG and purified by His tag affinity column with 90% purity. The recombinant pBD1(42) exhibited antimicrobial activity against both Gram-positive Staphylococcus aureus and Gram-negative E. coli including the multi-resistant E. coli. The minimum inhibitory concentrations (MICs) of recombinant pBD1(42) against tested bacteria were 100 µg/mL for E. coli and 80 µg/mL for S. aureus. In addition, pBD1(42) showed low hemolytic activity and high thermal stability. These properties are relevant for the biotechnological applications of the peptide.

Signal molecule-mediated hepatic cell communication during liver regeneration.

Liver regeneration is a complex and well-orchestrated process, during which hepatic cells are activated to produce large signal molecules in response to liver injury or mass reduction. These signal molecules, in turn, set up the connections and cross-talk among liver cells to promote hepatic recovery. In this review, we endeavor to summarize the network of signal molecules that mediates hepatic cell communication in the regulation of liver regeneration.

[Rehabilitation evaluation of Amatsu's tracheoesophageal shunt operation after total laryngectomy with sphincter mechanism].

OBJECTIVE: To evaluate rehabilitation effect of Amatsu's tracheoesophageal shunt operation after total laryngectomy with sphincter mechanism. METHODS: Voice rehabilitation were performed for 60 cases with Amatsu's tracheoesophageal shunt operation after total laryngectomy with sphincter mechanism, in which 20 cases were involved in post-operation radiation therapy. RESULTS: Fifty two (86.7%)cases developed speech with voice and swallow rehabilitation, but 1 case of them suffered water drip from his tracheoesophageal shunt when drinking. The other 8 (11.3%) cases developed swallow rehabilitation but failed in speech rehabilitation for pharyngeal fistula (4 cases, in which 1 had pre-operative radiation therapy), tracheoesophageal shunt obstruction (2 cases), dyspnea with unknown reason (1 cases), no desire to speech (1 cases). Furthermore, all the 20 cases who were involved in post-operative radiative therapy restore their speech and swallow capability finally. CONCLUSIONS: Amatsu's tracheoesophageal shunt operation with sphincter mechanism brought effective speech rehabilitation results for total laryngectomy even with post-operation radiation therapy.

Translocation of phospho-protein kinase Cs implies their roles in meiotic-spindle organization, polar-body emission and nuclear activity in mouse eggs.

The protein kinase Cs (PKCs) are a family of Ser/Thr protein kinases categorized into three subfamilies: classical, novel, and atypical. The phosphorylation of PKC in germ cells is not well defined. In this study, we described the subcellular localization of phopho-PKC in the process of mouse oocyte maturation, fertilization, and early embryonic mitosis. Confocal microscopy revealed that phospho-PKC (pan) was distributed abundantly in the nucleus at the germinal vesicle stage. After germinal vesicle breakdown, phospho-PKC was localized in the vicinity of the condensed chromosomes, distributed in the whole meiotic spindle, and concentrated at the spindle poles. After metaphase I, phospho-PKC was translocated gradually to the spindle mid-zone during emission of the first polar body. After sperm penetration and electrical activation, the distribution of phospho-PKC was moved from the spindle poles to the spindle mid-zone. After the extrusion of the second polar body (PB2) phospho-PKC was localized in the area between the oocyte and the PB2. In fertilized eggs, phospho-PKC was concentrated in the pronuclei except for the nucleolus. Phospho-PKC was dispersed after pronuclear envelope breakdown, but distributed on the entire spindle at mitotic metaphase. The results suggest that PKC activation may play important roles in regulating spindle organization and stabilization, polar-body extrusion, and nuclear activity during mouse oocyte meiosis, fertilization, and early embryonic mitosis.

[Tone recognition and electrode discrimination in prelingually deafened cochlear-implant listeners].

OBJECTIVE: To investigate tone recognition and electrode discrimination in prelingually deafened children with the Nucleus device, and to develop guidelines for customized mapping in the implant users. METHODS: Fourteen prelingually deafened children with cochlear implants participated in this study. Tone recognition was measured with a four-alternative, forced choice procedure from 25 consonant-vowel syllables, each of which had four tonal variations. Electrode discrimination was measured using a same-difference procedure on 7 pairs of electrodes covering the entire electrode array. RESULTS: Tone recognition ranged from 35% to 99% correct with a mean of 62.8% and standard deviation of 14.7% in these users. Electrode discrimination had the mean threshold of 3.4 +/- 0.9, with the best performance from the middle electrodes (E 14 and E 17) at 2.6 and the followed performance at the most apical electrode (E 20). CONCLUSION: The results showed significant individual differences from both tone recognition and electrode discrimination, but there is significant correlation between them.

[Implication of cochlear implantation in patients with enlarged vestibular aqueduct syndrome].

OBJECTIVE: To evaluate the intraoperative obstacles and post-operative outcomes of cochlear implantation in children with enlarged vestibular aqueduct syndrome. METHODS: Between May 1995 and June 2002, 10 patients with enlarged vestibular aqueduct syndrome received cochlear implantation in Pekin Union Medical College Hospital. The clinical records of 10 cases of enlarged vestibular aqueduct syndrome were analyzed retrospectively. RESULTS: Via cochleostomy pulsatile clear fluid gusher occurred in 8 cases, which were easily controlled by quickly inserting the electrode array and sealing the cochleostomy with muscle tissue in each instance. The implant was inserted without difficulty in all patients. There have been no post-operatively complications, and audiologic outcome of the 10 patients with cochlear implantation were almost the same as the other patients without inner ear malformations. Five cases of them can even speak better than the other prelingual deafness that may be attributed in part to postlingual deafness. CONCLUSIONS: Despite pulsatile clear fluid gusher in cochlear implantation, no post-operatively complications have been found, and the outcome of these 10 patients with cochlear implantation was excellent. Cochlear implantation can be safely and effectively performed in patients with profound sensorineural hearing loss (SNHL) associated with enlarged vestibular aqueduct syndrome.