T-Coffee: a web server for the multiple sequence alignment of protein and RNA sequences using structural information and homology extension.

This article introduces a new interface for T-Coffee, a consistency-based multiple sequence alignment program. This interface provides an easy and intuitive access to the most popular functionality of the package. These include the default T-Coffee mode for protein and nucleic acid sequences, the M-Coffee mode that allows combining the output of any other aligners, and template-based modes of T-Coffee that deliver high accuracy alignments while using structural or homology derived templates. These three available template modes are Expresso for the alignment of protein with a known 3D-Structure, R-Coffee to align RNA sequences with conserved secondary structures and PSI-Coffee to accurately align distantly related sequences using homology extension. The new server benefits from recent improvements of the T-Coffee algorithm and can align up to 150 sequences as long as 10,000 residues and is available from both http://www.tcoffee.org and its main mirror http://tcoffee.crg.cat.

Structural Insight into the Mode of Action of a Direct Inhibitor of Coregulator Binding to the Thyroid Hormone Receptor.

The development of nuclear hormone receptor antagonists that directly inhibit the association of the receptor with its essential coactivators would allow useful manipulation of nuclear hormone receptor signaling. We previously identified 3-(dibutylamino)-1-(4-hexylphenyl)-propan-1-one (DHPPA), an aromatic β-amino ketone that inhibits coactivator recruitment to thyroid hormone receptor β (TRβ), in a high-throughput screen. Initial evidence suggested that the aromatic β-enone 1-(4-hexylphenyl)-prop-2-en-1-one (HPPE), which alkylates a specific cysteine residue on the TRβ surface, is liberated from DHPPA. Nevertheless, aspects of the mechanism and specificity of action of DHPPA remained unclear. Here, we report an x-ray structure of TRβ with the inhibitor HPPE at 2.3-Å resolution. Unreacted HPPE is located at the interface that normally mediates binding between TRβ and its coactivator. Several lines of evidence, including experiments with TRβ mutants and mass spectroscopic analysis, showed that HPPE specifically alkylates cysteine residue 298 of TRβ, which is located near the activation function-2 pocket. We propose that this covalent adduct formation proceeds through a two-step mechanism: 1) β-elimination to form HPPE; and 2) a covalent bond slowly forms between HPPE and TRβ. DHPPA represents a novel class of potent TRβ antagonist, and its crystal structure suggests new ways to design antagonists that target the assembly of nuclear hormone receptor gene-regulatory complexes and block transcription.

Mixed spectral-structural classification of very high resolution images with summation kernels

In this paper, mixed spectral-structural kernel machines are proposed for the classification of very-high resolution images. The simultaneous use of multispectral and structural features (computed using morphological filters) allows a significant increase in classification accuracy of remote sensing images. Subsequently, weighted summation kernel support vector machines are proposed and applied in order to take into account the multiscale nature of the scene considered. Such classifiers use the Mercer property of kernel matrices to compute a new kernel matrix accounting simultaneously for two scale parameters. Tests on a Zurich QuickBird image show the relevance of the proposed method : using the mixed spectral-structural features, the classification accuracy increases of about 5%, achieving a Kappa index of 0.97. The multikernel approach proposed provide an overall accuracy of 98.90% with related Kappa index of 0.985.

A new early and automated MRI-based predictor of motor improvement after stroke.

OBJECTIVES: In this study, we investigated the structural plasticity of the contralesional motor network in ischemic stroke patients using diffusion magnetic resonance imaging (MRI) and explored a model that combines a MRI-based metric of contralesional network integrity and clinical data to predict functional outcome at 6 months after stroke. METHODS: MRI and clinical examinations were performed in 12 patients in the acute phase, at 1 and 6 months after stroke. Twelve age- and gender-matched controls underwent 2 MRIs 1 month apart. Structural remodeling after stroke was assessed using diffusion MRI with an automated measurement of generalized fractional anisotropy (GFA), which was calculated along connections between contralesional cortical motor areas. The predictive model of poststroke functional outcome was computed using a linear regression of acute GFA measures and the clinical assessment. RESULTS: GFA changes in the contralesional motor tracts were found in all patients and differed significantly from controls (0.001 ≤ p < 0.05). GFA changes in intrahemispheric and interhemispheric motor tracts correlated with age (p ≤ 0.01); those in intrahemispheric motor tracts correlated strongly with clinical scores and stroke sizes (p ≤ 0.001). GFA measured in the acute phase together with a routine motor score and age were a strong predictor of motor outcome at 6 months (r(2) = 0.96, p = 0.0002). CONCLUSION: These findings represent a proof of principle that contralesional diffusion MRI measures may provide reliable information for personalized rehabilitation planning after ischemic motor stroke. Neurology® 2012;79:39-46.

Closed loop electrical muscle stimulation in spinal cord injured rehabilitation

The effect of motor training using closed loop controlled Functional Electrical Stimulation (FES) on motor performance was studied in 5 spinal cord injured (SCI) volunteers. The subjects trained 2 to 3 times a week during 2 months on a newly developed rehabilitation robot (MotionMaker?). The FES induced muscle force could be adequately adjusted throughout the programmed exercises by the way of a closed loop control of the stimulation currents. The software of the MotionMaker? allowed spasms to be detected accurately and managed in a way to prevent any harm to the SCI persons. Subjects with incomplete SCI reported an increased proprioceptive awareness for motion and were able to achieve a better voluntary activation of their leg muscles during controlled FES. At the end of the training, the voluntary force of the 4 incomplete SCI patients was found increased by 388% on their most affected leg and by 193% on the other leg. Active mobilisation with controlled FES seems to be effective in improving motor function in SCI persons by increasing the sensory input to neuronal circuits involved in motor control as well as by increasing muscle strength.

In vivo Structural Imaging of the Cerebellum, the Contribution of Ultra-High Fields.

This review covers some of the contributions to date from cerebellar imaging studies performed at ultra-high magnetic fields. A short overview of the general advantages and drawbacks of the use of such high field systems for imaging is given. One of the biggest advantages of imaging at high magnetic fields is the improved spatial resolution, achievable thanks to the increased available signal-to-noise ratio. This high spatial resolution better matches the dimensions of the cerebellar substructures, allowing a better definition of such structures in the images. The implications of the use of high field systems is discussed for several imaging sequences and image contrast mechanisms. This review covers studies which were performed in vivo in both rodents and humans, with a special focus on studies that were directed towards the observation of the different cerebellar layers.

The INTERMED questionnaire for predicting return to work after a multidisciplinary rehabilitation program for chronic low back pain.

OBJECTIVES: To evaluate the performance of the INTERMED questionnaire score, alone or combined with other criteria, in predicting return to work after a multidisciplinary rehabilitation program in patients with non-specific chronic low back pain. METHODS: The INTERMED questionnaire is a biopsychosocial assessment and clinical classification tool that separates heterogeneous populations into subgroups according to case complexity. We studied 88 patients with chronic low back pain who followed an intensive multidisciplinary rehabilitation program on an outpatient basis. Before the program, we recorded the INTERMED score, radiological abnormalities, subjective pain severity, and sick leave duration. Associations between these variables and return to full-time work within 3 months after the end of the program were evaluated using one-sided Fisher tests and univariate logistic regression followed by multivariate logistic regression. RESULTS: The univariate analysis showed a significant association between the INTERMED score and return to work (P<0.001; odds ratio, 0.90; 95% confidence interval, 0.86-0.96). In the multivariate analysis, prediction was best when the INTERMED score and sick leave duration were used in combination (P=0.03; odds ratio, 0.48; 95% confidence interval, 0.25-0.93). CONCLUSION: The INTERMED questionnaire is useful for evaluating patients with chronic low back pain. It could be used to improve the selection of patients for intensive multidisciplinary programs, thereby improving the quality of care, while reducing healthcare costs.

Screening fo osteoporosis in elderly patients admitted to post-acute rehabilitation.

Background: Screening for osteoporosis is important in older patients admitted to post-acute rehabilitation. However, DXA measurement is sometimes difficult to perform because of difficulties in positioning the patient and artefacts (osteoarthritis, prosthesis). The objectives were to determine the prevalence of unknown clinical osteoporosis in rehab patients and to determine new strategies for identifying clinical osteoporosis in this population. Method: Over a 9-months period, patients consecutively admitted to post-acute rehabilitation were included in th stdy. Patients with osteoporosis diagnosis, and those with terminal illness or severe physical limitations were excluded. Patients underwent Bone Mineral Density (BMD) by DXA and Vertebral Fracture Assessment (VFA). Clinical osteoporosis was defined as BMD ≤-2.5 SD at any site (lumbar spine, femoral neck, total hip or distal radius), ≥1 vertebral fracture, ≥1 hip fracture, or another fragility fracture and BMD ≤-2 SD. Results: Overall, 102 (17.0%) of the 600 patients admitted to rehab refused to participate in the study or were unable to consent. Among the 498 remaining patients, 99 (19.9%) were excluded because of already known diagnosis of osteoporosis, 101 (20.3%) were excluded because of terminal illness, severe physical limitations, and 45 (9.0%) because of inability to perform DXA during the stay (death, hospital transfer). Overall, 253 patients were assessed with DXA and VFA (166 women, mean age 83±7 years, mean BMI 27±6 kg/m2, and 87 men, mean age 82±6 yrs, mean BMI 27±5 kg/m2). Of these, 70% had history of fall during the last 6 months and 9.1% had hip fracture history. Prevalence of osteoporotic vertebral fracture was 36% in women and 32% in men. Overall, 152 (60.1%) patients had clinical osteoporosis (women: 67%; men: 46%) according to above criteria. Hip fracture history and vertebral fracture assessment identified correctly 105 (69.1%) of these 152 patients. Conclusion: A high prevalence of osteoporosis was observed in this population of rehab patients. Osteoporosis status should be systematically assessed in these patients at high fall risk, at least with careful history of hip fracture and an assessment for vertebral fractures with spine X-ray.

Rééducation vasculaire du patient artériopathe [Vascular rehabilitation of patients suffering from peripheral arterial disease].

Rehabilitation programs represent an important and valuable tool for patients suffering various diseases. Supervised exercise programs for patients with peripheral arterial diseases have been shown to be efficacious in ameliorating walking performances and quality of life of such patients. With this regards the angiology service of the CHUV in Lausanne has established a multidisciplinary supervised program of vascular rehabilitation. This article describes organisation and characteristics of such a program.

Rehabilitation of atrophic maxilla: a review of 101 zygomatic implants

Introduction: Zygomatic implants are a good rehabilitation alternative for upper maxilla with severe bone reabsorption. These implants reduce the need for onlay-type bone grafting in the posterior sectors and for maxillary sinus lift procedures - limiting the use of bone grafts to the anterior zone of the upper jaw in those cases where grafting is considered necessary. Objective: To evaluate the survival of 101 zygomatic implants placed in upper maxilla presenting important bone reabsorption, with a follow-up of 1-72 months. Patients and methods: A retrospective study was made of 101 Zygoma® implants (Nobel Biocare, Göteborg, Sweden) placed in 54 patients with totally edentulous and atrophic upper maxilla, in the period between 1998-2004. There were 35 women and 19 men, subjected to rehabilitation in the form of fixed prostheses and overdentures using 1-2 zygomatic implants and 2-7 implants in the anterior maxillary zone. The principal study variables were smoking, a history of sinusitis, the degree of bone reabsorption, and peri-implant bone loss, among others. Results: The descriptive analysis of the 101 zygomatic implants placed in 54 patients with a mean age of 56 years (range 38-75) yielded a percentage survival of 96.04%, with four failed implants that were removed (two before and two after prosthetic loading). Nine patients were smokers, and none of the 54 subjects reported a history of sinus disorders. Discussion and conclusions: Zygomatic implants are designed for use in compromised upper maxilla. They allow the clinician to shorten the treatment time, affording an interesting alternative for fixed prosthetic rehabilitation. This study confirms that zygomatic bone offers predictable anchorage and acceptable support function for prostheses in atrophic jaws. However, these implants are not without complications. Longer-term evaluations are needed of zygomatic implant survival in order to establish a correct clinical prognosis

Local alignment refinement using structural assessment.

Homology modeling is the most commonly used technique to build a three-dimensional model for a protein sequence. It heavily relies on the quality of the sequence alignment between the protein to model and related proteins with a known three dimensional structure. Alignment quality can be assessed according to the physico-chemical properties of the three dimensional models it produces.In this work, we introduce fifteen predictors designed to evaluate the properties of the models obtained for various alignments. They consist of an energy value obtained from different force fields (CHARMM, ProsaII or ANOLEA) computed on residue selected around misaligned regions. These predictors were evaluated on ten challenging test cases. For each target, all possible ungapped alignments are generated and their corresponding models are computed and evaluated.The best predictor, retrieving the structural alignment for 9 out of 10 test cases, is based on the ANOLEA atomistic mean force potential and takes into account residues around misaligned secondary structure elements. The performance of the other predictors is significantly lower. This work shows that substantial improvement in local alignments can be obtained by careful assessment of the local structure of the resulting models.