Automatic prediction of functional site regions in low-resolution protein structures

World-wide structural genomics initiatives are rapidly accumulating structures for which limited functional information is available. Additionally, state-of-the art structural prediction programs are now capable of generating at least low resolution structural models of target proteins. Accurate detection and classification of functional sites within both solved and modelled protein structures therefore represents an important challenge. We present a fully automatic site detection method, FuncSite, that uses neural network classifiers to predict the location and type of functionally important sites in protein structures. The method is designed primarily to require only backbone residue positions without the need for specific side-chain atoms to be present. In order to highlight effective site detection in low resolution structural models FuncSite was used to screen model proteins generated using mGenTHREADER on a set of newly released structures. We found effective metal site detection even for moderate quality protein models illustrating the robustness of the method.

Morphological and functional characteristics of chilled semen obtained from domestic feline epididymides (Felis catus)

The objective of this study was to determine morphological and functional characteristics of semen retrieved from the feline epididymis before and after cooling. Sixteen adult male cats were orchiectomized. The distal portion of the epididymis and proximal part of the deferent ducts were dissected and squeezed to obtain their content. After centrifugation, the supernatant was removed, sperm were resuspended in a 0.9 mL Tris-fructose-citric acid extender containing 20% egg yolk, aliquoted into three 0.3 mL samples, placed in a refrigerator (4.8 degrees C) and cooled (0.5 degrees C/min). Semen evaluations were performed on four occassions: immediately after epididymal sperm retrieval (TO), and at 24 h (T-1), 48 h (T-2) and 72 h (T-3) after cooling. on each occasion, progressive motility, vigor and sperm morphology were determined. Mean motility and vigor decreased (P < 0.05) between each successive examination. Although the majority of sperm cell damage occurred within the first 24 h, there was a decrease (P < 0.05) in mean percentage of morphologically normal sperm between To and each evaluated time (T-1, T-2, T-3) after cooling, due to an increase in coiled and bent sperm tails. Further studies are needed to evaluate the effects of cooling on the fertilizing capacity of cat epididymal spermatozoa in assisted reproduction programs. (c) 2006 Elsevier B.V. All rights reserved.

Exercise programs improve mobility and balance in people with Parkinson's disease

Compromised balance and loss of mobility are among the major consequences of Parkinson's disease (PD). The literature documents numerous effective interventions for improving balance and mobility. The purpose of this study was to verify the effectiveness of two exercise programs on balance and mobility in people with idiopathic PD. Thirty-four participants, with idiopathic PD that ranged from Stage I to Stage III on the Hoehn & Yahr (H&Y) scale, were assigned to two groups. Group 1 (n = 21; 67±9 years old) was engaged in an intensive exercise program (aerobic capacity, flexibility, strength, motor coordination and balance) for 6 months: 72 sessions, 3 times a week, 60 minutes per session; while Group 2 (n = 13; 69±8 years old) participated in an adaptive program (flexibility, strength, motor coordination and balance) for 6 months: 24 sessions, once a week, 60 minutes per session. Balance and basic functional mobility were assessed in pre- and post-tests by means of the Berg Balance Scale and the Timed Up and Go Test. Before and after the interventions, groups were similar in clinical conditions (H&Y, UPDRS, and Mini-Mental). A MANOVA 2 (programs) by 2 (moments) revealed that both groups were affected by the exercise intervention. Univariate analyses showed that participants improved their mobility and balance from pre- to post-test. There were no differences between groups in either mobility or balance results. Both the intensive and adaptive exercise programs improved balance and mobility in patients with PD. © 2009 Elsevier Ltd. All rights reserved.

Effects of Water-Based and Callisthenic Exercise on Freezing of Gait, Postural Control, and Functional Independence in Patients With Mild to Moderate Parkinson Disease

Objective: This study aimed to analyze and compare the role of a water-based exercise program versus a combination of water and callisthenic exercises on postural control, functional independence, and freezing of gait (FOG) in patients with mild to moderate Parkinson disease.Methods: Twenty-five community-dwelling participants with idiopathic Parkinson disease were recruited. Of these, 9 participants took part in a water-based program of physical exercises and the other 16 participants took part in a combined program that consisted of callisthenic exercises plus an aquatic exercise session. Both programs were 16 weeks in duration. The clinical evaluation assessed the festination by means of the FOG score test; postural control was verified by means of the balance test of the short physical performance battery, and the Spanish validated version of the Unified Parkinson's Disease Rating Scale part 2 was used to assess functional independence. Participants were evaluated before and after 16 weeks of both proposed programs.Results: The results showed improvement in FOG for both groups, although a significant main effect was observed only in the patients who performed the callisthenic exercise plus an aquatic exercise program. Postural control did not show significant improvements after both proposed physical exercise programs as soon as functional autonomy. Our preliminary results suggest that training sessions with the combination of water plus callisthenic exercises may be a useful physical rehabilitation strategy for individuals with mild to moderate Parkinson disease who have FOG.

EFFECTS OF MUSCULAR STRETCHING AND SEGMENTAL STABILIZATION ON FUNCTIONAL DISABILITY AND PAIN IN PATIENTS WITH CHRONIC LOW BACK PAIN: A RANDOMIZED, CONTROLLED TRIAL

Objective: The purpose of this study was to compare the effects of 2 exercise programs, segmental stabilization exercises (SSEs) and stretching of trunk and hamstrings muscles, on functional disability, pain, and activation of the transversus abdominis muscle (TrA), in individuals with chronic low back pain. Methods: A total of 30 participants were enrolled in this study and randomly assigned to 1 of 2 groups as a function of intervention. In the segmental stabilization group (SS), exercises focused on the TrA and lumbar multifidus muscles, whereas in the stretching group (ST), exercises focused on stretching the erector spinae, hamstrings, and triceps surae. Severity of pain (visual analog scale and McGill pain questionnaire) and functional disability (Oswestry disability questionnaire) and TrA muscle activation capacity (Pressure Biofeedback Unit, or PBU) were compared as a function of intervention. Interventions lasted 6 weeks, and sessions happened twice a week (30 minutes each). Analysis of variance was used for intergroup and intragroup comparisons. Results: As compared with baseline, both treatments were effective in relieving pain and improving disability (P < .001). Those in the SS group had significantly higher gains for all variables. The stretching group did not effectively activate the TrA (P = .94). Conclusion: Both techniques improved pain and reduced disability. In this study, SS was superior to muscular stretching for the measured variables associated with chronic low back pain. (J Manipulative Physiol Ther 2012;35:279-285)

Low dynamic muscle strength and its associations with fatigue, functional performance, and quality of life in premenopausal patients with systemic lupus erythematosus and low disease activity: a case–control study

Abstract Background The purpose of the present study was to compare dynamic muscle strength, functional performance, fatigue, and quality of life in premenopausal systemic lupus erythematosus (SLE) patients with low disease activity versus matched-healthy controls and to determine the association of dynamic muscle strength with fatigue, functional performance, and quality of life in SLE patients. Methods We evaluated premenopausal (18–45 years) SLE patients with low disease activity (Systemic lupus erythematosus disease activity index [SLEDAI]: mean 1.5 ± 1.2). The control (n = 25) and patient (n = 25) groups were matched by age, physical characteristics, and the level of physical activities in daily life (International Physical Activity Questionnaire IPAQ). Both groups had not participated in regular exercise programs for at least six months prior to the study. Dynamic muscle strength was assessed by one-repetition maximum (1-RM) tests. Functional performance was assessed by the Timed Up and Go (TUG), in 30-s test a chair stand and arm curl using a 2-kg dumbbell and balance test, handgrip strength and a sit-and-reach flexibility test. Quality of life (SF-36) and fatigue were also measured. Results The SLE patients showed significantly lower dynamic muscle strength in all exercises (leg press 25.63%, leg extension 11.19%, leg curl 15.71%, chest press 18.33%, lat pulldown 13.56%, 1-RM total load 18.12%, P < 0.001-0.02) compared to the controls. The SLE patients also had lower functional performance, greater fatigue and poorer quality of life. In addition, fatigue, SF-36 and functional performance accounted for 52% of the variance in dynamic muscle strength in the SLE patients. Conclusions Premenopausal SLE patients with low disease activity showed lower dynamic muscle strength, along with increased fatigue, reduced functional performance, and poorer quality of life when compared to matched controls.

Functional markers for gene mapping and genetic diversity studies in sugarcane

Abstract Background The database of sugarcane expressed sequence tags (EST) offers a great opportunity for developing molecular markers that are directly associated with important agronomic traits. The development of new EST-SSR markers represents an important tool for genetic analysis. In sugarcane breeding programs, functional markers can be used to accelerate the process and select important agronomic traits, especially in the mapping of quantitative traits loci (QTL) and plant resistant pathogens or qualitative resistance loci (QRL). The aim of this work was to develop new simple sequence repeat (SSR) markers in sugarcane using the sugarcane expressed sequence tag (SUCEST database). Findings A total of 365 EST-SSR molecular markers with trinucleotide motifs were developed and evaluated in a collection of 18 genotypes of sugarcane (15 varieties and 3 species). In total, 287 of the EST-SSRs markers amplified fragments of the expected size and were polymorphic in the analyzed sugarcane varieties. The number of alleles ranged from 2-18, with an average of 6 alleles per locus, while polymorphism information content values ranged from 0.21-0.92, with an average of 0.69. The discrimination power was high for the majority of the EST-SSRs, with an average value of 0.80. Among the markers characterized in this study some have particular interest, those that are related to bacterial defense responses, generation of precursor metabolites and energy and those involved in carbohydrate metabolic process. Conclusions These EST-SSR markers presented in this work can be efficiently used for genetic mapping studies of segregating sugarcane populations. The high Polymorphism Information Content (PIC) and Discriminant Power (DP) presented facilitate the QTL identification and marker-assisted selection due the association with functional regions of the genome became an important tool for the sugarcane breeding program.

Seeking tools for image fusion between computed tomography, structural and functional magnetic resonance methods for applications in neurosurgery

OBJECTIVE: To evaluate tools for the fusion of images generated by tomography and structural and functional magnetic resonance imaging. METHODS: Magnetic resonance and functional magnetic resonance imaging were performed while a volunteer who had previously undergone cranial tomography performed motor and somatosensory tasks in a 3-Tesla scanner. Image data were analyzed with different programs, and the results were compared. RESULTS: We constructed a flow chart of computational processes that allowed measurement of the spatial congruence between the methods. There was no single computational tool that contained the entire set of functions necessary to achieve the goal. CONCLUSION: The fusion of the images from the three methods proved to be feasible with the use of four free-access software programs (OsiriX, Register, MRIcro and FSL). Our results may serve as a basis for building software that will be useful as a virtual tool prior to neurosurgery.

Transcriptional regulation and functional characterization of the tumor suppressor genes Hugl-1 and Hugl-2

Cancer is a multi-step process in which both the activation of oncogenes and the inactivation of tumor suppressor genes alter the normal cellular programs to a state of proliferation and growth. The regulation of a number of tumor suppressor genes and the mechanism underlying the tumor suppression have been intensively studied. Hugl-1 and Hugl-2, the human homologues of Drosophila lgl are shown to be down-regulated in a variety of cancers including breast, colon, lung and melanoma, but the mechanism responsible for loss of expression is not yet known. The regulation of gene expression is influenced by factors inducing or repressing transcription. The present study was focused on the identification and characterization of the active promoters of Hugl-1 and Hugl-2. Further, the regulation of the promoter and functional consequences of this regulation by specific transcription factors was analyzed. Experiments to delineate the function of the mouse homologue of Hugl-2, mgl2 using transgenic mice model were performed. This study shows that the active promoter for both Hugl-1 and Hugl-2 is located 1000bp upstream of transcription start sites. The study also provides first insight into the regulation of Hugl-2 by an important EMT transcriptional regulator, Snail. Direct binding of Snail to four E-boxes present in Hugl-2 promoter region results in repression of Hugl-2 expression. Hugl-1 and Hugl-2 plays pivotal role in establishment and maintenance of cell polarity in a diversity of cell types and organisms. Loss of epithelial cell polarity is a prerequisite for cancer progression and metastasis and is an important step in inducing EMT in cells. Regulation of Hugl-2 by Snail suggests one of the initial events towards loss of epithelial cell polarity during Snail-mediated EMT. Another important finding of this study is the induction of Hugl-2 expression can reverse the Snail-driven EMT. Inducing Hugl-2 in Snail expressing cells results in the re-expression of epithelial markers E-cadherin and Cytokeratin-18. Further, Hugl-2 also reduces the rate of tumor growth, cell migration and induces the epithelial phenotype in 3D culture model in cells expressing Snail. Studies to gain insight into the signaling pathways involved in reversing Snail-mediated EMT revealed that induction of Hugl-2 expression interferes with the activation of extracellular receptor kinase, Erk. Functional aspects of mammalian lgl in vivo was investigated by establishing mgl2 conditional knockout mice. Though disruption of mgl2 gene in hepatic tissues did not alter the growth and development, ubiquitous disruption of mgl2 gene causes embryonic lethality which is evident by the fact that no mgl2-/- mice were born.

Multidimensional preventive home visit programs for community-dwelling older adults: a systematic review and meta-analysis of randomized controlled trials

BACKGROUND: Multidimensional preventive home visit programs aim at maintaining health and autonomy of older adults and preventing disability and subsequent nursing home admission, but results of randomized controlled trials (RCTs) have been inconsistent. Our objective was to systematically review RCTs examining the effect of home visit programs on mortality, nursing home admissions, and functional status decline. METHODS: Data sources were MEDLINE, EMBASE, Cochrane CENTRAL database, and references. Studies were reviewed to identify RCTs that compared outcome data of older participants in preventive home visit programs with control group outcome data. Publications reporting 21 trials were included. Data on study population, intervention characteristics, outcomes, and trial quality were double-extracted. We conducted random effects meta-analyses. RESULTS: Pooled effects estimates revealed statistically nonsignificant favorable, and heterogeneous effects on mortality (odds ratio [OR] 0.92, 95% confidence interval [CI], 0.80-1.05), functional status decline (OR 0.89, 95% CI, 0.77-1.03), and nursing home admission (OR 0.86, 95% CI, 0.68-1.10). A beneficial effect on mortality was seen in younger study populations (OR 0.74, 95% CI, 0.58-0.94) but not in older populations (OR 1.14, 95% CI, 0.90-1.43). Functional decline was reduced in programs including a clinical examination in the initial assessment (OR 0.64, 95% CI, 0.48-0.87) but not in other trials (OR 1.00, 95% CI, 0.88-1.14). There was no single factor explaining the heterogenous effects of trials on nursing home admissions. CONCLUSION: Multidimensional preventive home visits have the potential to reduce disability burden among older adults when based on multidimensional assessment with clinical examination. Effects on nursing home admissions are heterogeneous and likely depend on multiple factors including population factors, program characteristics, and health care setting.

MEETING THE NEEDS OF HANDICAPPED CHILDREN: A STUDY OF EDUCATIONAL AND HEALTH CARE SERVICES PROVIDED TO PRE-KINDERGARTEN CHILDREN IN THE HOUSTON INDEPENDENT SCHOOL DISTRICT EARLY CHILDHOOD PROGRAM FOR THE HANDICAPPED (PARENT SATISFACTION, FUNCTIONAL STATUS, PSYCHOSOCIAL DEVELOPMENT)

The Education for All Handicapped Children Act of 1975, P.L. 94-142, created a new challenge for the nation's public school systems. During 1982-1983, a national study, called the "Collaborative Study of Children with Special Needs", was conducted in 5 metropolitan school districts to evaluate the effectiveness of education and health care services of children in kindergarten to 6th grade being provided under P.L. 94-142 programs. This dissertation (the Substudy) was undertaken to augment the findings of the Collaborative Study. The purpose of this study was to develop a database to provide descriptive information on the demographic, service and health characteristics of a small group of 3 and 4 year old handicapped children served by the Houston Independent School District (HISD) during 1982-1983.^ The study involved a stratified sample of 105 three and four year old children divided into 3 groups according to type of handicapping condition.^ The results of the study gave a clearer picture of the demographic characteristics of these Pre-K children. Specifically, sex ratio was approximately one, lower than the national norm. Family and socioeconomic characteristics were assessed.^ The study used an independence/dependence index composed of 11 items on the parent questionnaire to assess the level of functional independence of each child. An association was found between index scores and parent-reported effects of the child on family activity. Parents who said that their child's condition had affected the family's job situation, housing accomodations, vacation plans, marriage, choice of friends and social activities were also more likely to report less independence in the child. In addition, many of the Substudy children had extensive care-taking needs reflected in specific components of the index such as dressing, feeding, toileting or moving about the house.^ In general the results of the Pre-K Substudy indicate that at the early childhood level, the HISD special education program is functioning well in most areas and that parents are very satisfied with the program. (Abstract shortened with permission of author.)^

Global distributions of diatoms abundance, biovolume and biomass - Gridded data product (NetCDF) - Contribution to the MAREDAT World Ocean Atlas of Plankton Functional Types

This study is a first effort to compile the largest possible body of data available from different plankton databases as well as from individual published or unpublished datasets regarding diatom distribution in the world ocean. The data obtained originate from time series studies as well as spatial studies. This effort is supported by the Marine Ecosystem Data (MAREDAT) project, which aims at building consistent data sets for the main PFTs (Plankton Functional Types) in order to help validate biogeochemical ocean models by using converted C biomass from abundance data. Diatom abundance data were obtained from various research programs with the associated geolocation and date of collection, as well as with a taxonomic information ranging from group down to species. Minimum, maximum and average cell size information were mined from the literature for each taxonomic entry, and all abundance data were subsequently converted to biovolume and C biomass using the same methodology.

Two efficient representations for set-sharing analysis in logic programs

Set-Sharing analysis, the classic Jacobs and Langen's domain, has been widely used to infer several interesting properties of programs at compile-time such as occurs-check reduction, automatic parallelization, flnite-tree analysis, etc. However, performing abstract uniflcation over this domain implies the use of a closure operation which makes the number of sharing groups grow exponentially. Much attention has been given in the literature to mitígate this key inefficiency in this otherwise very useful domain. In this paper we present two novel alternative representations for the traditional set-sharing domain, tSH and tNSH. which compress efficiently the number of elements into fewer elements enabling more efficient abstract operations, including abstract uniflcation, without any loss of accuracy. Our experimental evaluation supports that both representations can reduce dramatically the number of sharing groups showing they can be more practical solutions towards scalable set-sharing.

An abstract machine based execution model for computer architecture design and efficient implementation of logic programs in parallel.

The term "Logic Programming" refers to a variety of computer languages and execution models which are based on the traditional concept of Symbolic Logic. The expressive power of these languages offers promise to be of great assistance in facing the programming challenges of present and future symbolic processing applications in Artificial Intelligence, Knowledge-based systems, and many other areas of computing. The sequential execution speed of logic programs has been greatly improved since the advent of the first interpreters. However, higher inference speeds are still required in order to meet the demands of applications such as those contemplated for next generation computer systems. The execution of logic programs in parallel is currently considered a promising strategy for attaining such inference speeds. Logic Programming in turn appears as a suitable programming paradigm for parallel architectures because of the many opportunities for parallel execution present in the implementation of logic programs. This dissertation presents an efficient parallel execution model for logic programs. The model is described from the source language level down to an "Abstract Machine" level suitable for direct implementation on existing parallel systems or for the design of special purpose parallel architectures. Few assumptions are made at the source language level and therefore the techniques developed and the general Abstract Machine design are applicable to a variety of logic (and also functional) languages. These techniques offer efficient solutions to several areas of parallel Logic Programming implementation previously considered problematic or a source of considerable overhead, such as the detection and handling of variable binding conflicts in AND-Parallelism, the specification of control and management of the execution tree, the treatment of distributed backtracking, and goal scheduling and memory management issues, etc. A parallel Abstract Machine design is offered, specifying data areas, operation, and a suitable instruction set. This design is based on extending to a parallel environment the techniques introduced by the Warren Abstract Machine, which have already made very fast and space efficient sequential systems a reality. Therefore, the model herein presented is capable of retaining sequential execution speed similar to that of high performance sequential systems, while extracting additional gains in speed by efficiently implementing parallel execution. These claims are supported by simulations of the Abstract Machine on sample programs.

Human midbrain precursors activate the expected developmental genetic program and differentiate long-term to functional A9 dopamine neurons in vitro. Enhancement by Bcl-XL

Understanding the molecular programs of the generation of human dopaminergic neurons (DAn) from their ventral mesencephalic (VM) precursors is of key importance for basic studies, progress in cell therapy, drug screening and pharmacology in the context of Parkinson's disease. The nature of human DAn precursors in vitro is poorly understood, their properties unstable, and their availability highly limited. Here we present positive evidence that human VM precursors retaining their genuine properties and long-term capacity to generate A9 type Substantia nigra human DAn (hVM1 model cell line) can be propagated in culture. During a one month differentiation, these cells activate all key genes needed to progress from pro-neural and prodopaminergic precursors to mature and functional DAn. For the first time, we demonstrate that gene cascades are correctly activated during differentiation, resulting in the generation of mature DAn. These DAn have morphological and functional properties undistinguishable from those generated by VM primary neuronal cultures. In addition, we have found that the forced expression of Bcl-XL induces an increase in the expression of key developmental genes (MSX1, NGN2), maintenance of PITX3 expression temporal profile, and also enhances genes involved in DAn long-term function, maintenance and survival (EN1, LMX1B, NURR1 and PITX3). As a result, Bcl-XL anticipates and enhances DAn generation.