The molecular basis of ubiquitin-like protein NEDD8 deamidation by the bacterial effector protein Cif

The cycle inhibiting factors (Cifs) are a family of translocated effector proteins, found in diverse pathogenic bacteria, that interfere with the host cell cycle by catalyzing the deamidation of a specific glutamine residue (Gln40) in NEDD8 and the related protein ubiquitin. This modification prevents recycling of neddylated cullin-RING ligases, leading to stabilization of various cullin-RING ligase targets, and also prevents polyubiquitin chain formation. Here, we report the crystal structures of two Cif/NEDD8 complexes, revealing a conserved molecular interface that defines enzyme/substrate recognition. Mutation of residues forming the interface suggests that shape complementarity, rather than specific individual interactions, is a critical feature for complex formation. We show that Cifs from diverse bacteria bind NEDD8 in vitro and conclude that they will all interact with their substrates in the same way. The "occluding loop" in Cif gates access to Gln40 by forcing a conformational change in the C terminus of NEDD8. We used native PAGE to follow the activity of Cif from the human pathogen Yersinia pseudotuberculosis and selected variants, and the position of Gln40 in the active site has allowed us to propose a catalytic mechanism for these enzymes.     

Reduction in nerve root compression by the nucleus pulposus after Feng's Spinal Manipulation

Ninety-four patients with lumbar intervertebral disc herniation were enrolled in this study. Of these, 48 were treated with Feng’s Spinal Manipulation, hot fomentation, and bed rest (treatment group). The remaining 46 patients were treated with hot fomentation and bed rest only (control group). After 3 weeks of treatment, clinical parameters including the angle of straight-leg raising, visual analogue scale pain score, and Japanese Orthopaedic Association score for low back pain were improved. The treatment group had significantly better improvement in scores than the control group. Magnetic resonance myelography three-dimensional reconstruction imaging of the vertebral canal demonstrated that filling of the compressed nerve root sleeve with cerebrospinal fluid increased significantly in the treatment group. The diameter of the nerve root sleeve was significantly larger in the treatment group than in the control group. However, the sagittal diameter index of the herniated nucleus pulposus and the angle between the nerve root sleeve and the thecal sac did not change significantly in either the treatment or control groups. The effectiveness of Feng’s Spinal Manipulation for the treatment of symptoms associated with lumbar intervertebral disc herniation may be attributable to the relief of nerve root compression, without affecting the herniated nucleus pulposus or changing the morphology or position of the nerve root.     

Association between heart rate variability and manual pulse rate

Introduction:

One model for neurological assessment in chiropractic pertains to autonomic variability, tested commonly with heart rate variability (HRV). Since HRV may not be convenient to use on all patient visits, more user-friendly methods may help fill-in the gaps. Accordingly, this study tests the association between manual pulse rate and heart rate variability. The manual rates were also compared to the heart rate derived from HRV.

Methods:

Forty-eight chiropractic students were examined with heart rate variability (SDNN and mean heart rate) and two manual radial pulse rate measurements. Inclusion criteria consisted of participants being chiropractic students. Exclusion criteria for 46 of the participants consisted of a body mass index being greater than 30, age greater than 35, and history of: a) dizziness upon standing, b) treatment of psychiatric disorders, and c) diabetes. No exclusion criteria were applied to the remaining two participants who were also convenience sample volunteers. Linear associations between the manual pulse rate methods and the two heart rate variability measures (SDNN and mean heart) were tested with Pearson’s correlation and simple linear regression.

Results:

Moderate strength inverse (expected) correlations were observed between both manual pulse rate methods and SDNN (r = −0.640, 95% CI −0.781, −0.435; r = −0.632, 95% CI −0.776, −0.425). Strong direct (expected) relationships were observed between the manual pulse rate methods and heart rate derived from HRV technology (r = 0.934, 95% CI 0.885, 0.962; r = 0.941, 95% CI 0.897, 0.966).

Conclusion:

Manual pulse rates may be a useful option for assessing autonomic variability. Furthermore, this study showed a strong relationship between manual pulse rates and heart rate derived from HRV technology.     

Compare the Traditional Chinese Medicine Manipulation With Rehabilitation on In-Patients After Total Knee Arthroplasty

This prospective, randomized, and controlled study was conducted to assess Traditional Chinese Medicine (TCM) for pain control, alone and in conjunction with a standard inpatient rehabilitation program, during the five days immediately following total knee arthroplasty (TKA). Forty-one patients undergoing primary unilateral TKA between February, 2010 and January, 2011 were randomly assigned to one of three groups. Levels of pain were then monitored using a Visual Analogue Scale (VAS). Significant alleviation of pain and diminution of flexion contractures were achieved using TCM, with and without standard rehabilitation. These outcomes support use of TCM immediately post-TKA to facilitate patient recovery.     

华南地区正常成人股骨远端髁扭转角测量及其临床意义

目的探讨华南地区正常成人的膝关节股骨远端髁扭转角具体数值,并分析其在性别和侧别间有无统计学差异。方法招募华南地区（往上数五代以内均生在华南地区,包括广东、广西或者海南）正常成人志愿者71例（142膝）,男38例（76膝）,女33例（66膝）,年龄20～45岁,平均30．56岁,体重40—80kg,平均59．90kg,身高151—185cm,平均167．80cm。通过螺旋CT扫描志愿者膝关节,所得原始数据（DICOM3）刻录为光盘,导入MIMICS10．01中,选择通过股骨内外上髁的层面进行测量股骨远端髁扭转角。结果所测得华南地区正常成人的股骨远端髁扭转角：男性为（6．20°±2．03°）,女性为（7．19°±1．78°）,均值为（6．66°±1．97°）,性别之间差异有统计学意义（t=3．077,P〈0．01）;左侧为（6．86°±1．92°）,右侧为（6．45°±2．02°）,侧别间无统计学差异（t=1．238,P〉0．05）。总体股骨远端髁扭转角为（2．39°～11．34°）,均值（6．66°±1．97°）。结论对华南人的人工全膝关节置换术中,传统的外旋3。截骨可能会导致对线不佳,应该适当提高旋转对线的外旋度数。     

《医宗金鉴》对张氏正骨流派学术思想的影响

《医宗金鉴》是清代由政府组织编写的综合性医学丛书,其立论精辟,尤重实用,对后世影响甚大。湖南岳阳张氏正骨始于清末,在张氏正骨发展过程中,不断吸收并结合了《医宗金鉴》等医学著作和民间特色技术,在继承的基础上体现了创新,强调“筋骨并重,内外调和”、“去瘀生新,气血相和”,逐渐形成了以“和”为核心的张氏正骨学术思想。本文着重探讨《医宗金鉴》对湖南岳阳张氏正骨相关学术思想和实际应用的影响。认为张氏正骨流派在正骨手法、内外方药、针推技术等方面继承了《医宗金鉴》主要的学术理念,并不断发展创新骨伤技术方法、药物应用等。     

The effects of toxoplasma infection on rodent behavior are dependent on dose of the stimulus

Parasite Toxoplasma gondii blocks the innate aversion of rats for cat urine, putatively increasing the likelihood of a cat predating a rat. This is thought to reflect an adaptive behavioral manipulation, because toxoplasma can reproduce only in cat intestines. While it will be adaptive for the parasite to cause an absolute behavioral change, fitness costs associated with the manipulation itself suggest that the change is optimized and not maximized. We investigate these conflicting suggestions in the present report. Furthermore, exposure to cat odor causes long-lasting acquisition of learnt fear in the rodents. If toxoplasma manipulates emotional valence of cat odor rather than just sensory response, infection should affect learning driven by the aversive properties of the odor. As a second aim of the present study, we investigate this assertion. We demonstrate that behavioral changes in rodents induced by toxoplasma infection do not represent absolute all-or-none effects. Rather, these effects follow a non-monotonous function dependent on strength of stimulus, roughly resembling an inverted-U curve. Furthermore, infection affects conditioning to cat odor in a manner dependent upon strength of unconditioned stimulus employed. Non-monotonous relationship between behavioral manipulation and strength of cat odor agrees with the suggestion that a dynamic balance exists between benefit obtained and costs incurred by the parasite during the manipulation. This report also demonstrates that toxoplasma affects emotional valence of the cat odor as indicated by altered learned fear induced by cat odor.