bluuebunny/crossref_metadata_2025_split huggingface dataset:
Primate-specific evolution of an LDLR enhancer
Authors: Wang Qian-fei , Prabhakar Shyam , Wang Qianben , Moses Alan M , Chanan Sumita , Brown Myles , Eisen Michael B , Cheng Jan-Fang , Rubin Edward M , Boffelli Dario 
Published: August 2006

BackgroundSequence changes in regulatory regions have often been invoked to explain phenotypic divergence among species, but molecular examples of this have been difficult to obtain.
Results
In this study we identified an anthropoid primate-specific sequence element that contributed to the regulatory evolution of the low-density lipoprotein receptor. Using a combination of close and distant species genomic sequence comparisons coupled with in vivo and in vitro studies, we found that a functional cholesterol-sensing sequence motif arose and was fixed within a pre-existing enhancer in the common ancestor of anthropoid primates.

Conclusion
Our study demonstrates one molecular mechanism by which ancestral mammalian regulatory elements can evolve to perform new functions in the primate lineage leading to human.
Combinatorial RNA interference in Caenorhabditis elegans reveals that redundancy between gene duplicates can be maintained for more than 80 million years of evolution
Authors: Tischler Julia , Lehner Ben , Chen Nansheng , Fraser Andrew G 
Published: August 2006

Abstract
Background
Systematic analyses of loss-of-function phenotypes have been carried out for most genes in Saccharomyces cerevisiae, Caenorhabditis elegans, and Drosophila melanogaster. Although such studies vastly expand our knowledge of single gene function, they do not address redundancy in genetic networks. Developing tools for the systematic mapping of genetic interactions is thus a key step in exploring the relationship between genotype and phenotype.

Results
We established conditions for RNA interference (RNAi) in C. elegans to target multiple genes simultaneously in a high-throughput setting. Using this approach, we can detect the great majority of previously known synthetic genetic interactions. We used this assay to examine the redundancy of duplicated genes in the genome of C. elegans that correspond to single orthologs in S. cerevisiae or D. melanogaster and identified 16 pairs of duplicated genes that have redundant functions. Remarkably, 14 of these redundant gene pairs were duplicated before the divergence of C. elegans and C. briggsae 80-110 million years ago, suggesting that there has been selective pressure to maintain the overlap in function between some gene duplicates.

Conclusion
We established a high throughput method for examining genetic interactions using combinatorial RNAi in C. elegans. Using this technique, we demonstrated that many duplicated genes can retain redundant functions for more than 80 million years of evolution. This provides strong support for evolutionary models that predict that genetic redundancy between duplicated genes can be actively maintained by natural selection and is not just a transient side effect of recent gene duplication events.
Statistical assessment of the global regulatory role of histone acetylation in Saccharomyces cerevisiae
Authors: Yuan Guo-Cheng , Ma Ping , Zhong Wenxuan , Liu Jun S 
Published: August 2006

Abstract
Background
Histone acetylation plays important but incompletely understood roles in gene regulation. A comprehensive understanding of the regulatory role of histone acetylation is difficult because many different histone acetylation patterns exist and their effects are confounded by other factors, such as the transcription factor binding sequence motif information and nucleosome occupancy.

Results
We analyzed recent genomewide histone acetylation data using a few complementary statistical models and tested the validity of a cumulative model in approximating the global regulatory effect of histone acetylation. Confounding effects due to transcription factor binding sequence information were estimated by using two independent motif-based algorithms followed by a variable selection method. We found that the sequence information has a significant role in regulating transcription, and we also found a clear additional histone acetylation effect. Our model fits well with observed genome-wide data. Strikingly, including more complicated combinatorial effects does not improve the model's performance. Through a statistical analysis of conditional independence, we found that H4 acetylation may not have significant direct impact on global gene expression.

Conclusion
Decoding the combinatorial complexity of histone modification requires not only new data but also new methods to analyze the data. Our statistical analysis confirms that histone acetylation has a significant effect on gene transcription rates in addition to that attributable to upstream sequence motifs. Our analysis also suggests that a cumulative effect model for global histone acetylation is justified, although a more complex histone code may be important at specific gene loci. We also found that the regulatory roles among different histone acetylation sites have important differences.
Comparative inflammatory properties of staphylococcal superantigenic enterotoxins SEA and SEG: implications for septic shock
Authors: Dauwalder Olivier , Thomas Damien , Ferry Tristan , Debard Anne-Lise , Badiou Cédric , Vandenesch François , Etienne Jerome , Lina Gerard , Monneret Guillaume 
Published: August 2006

Abstract
The severity of Staphylococcus aureus sepsis is positively associated with staphylococcal enterotoxin A (SEA) and negatively associated with the enterotoxin gene cluster (egc), which encodes five staphylococcal enterotoxins [1]. We postulated that the variable, clinical severity of S. aureus sepsis might be a result of differences in the inflammatory properties of staphylococcal superantigens. We therefore compared the inflammatory properties of SEA with those of staphylococcal entérotoxin G (SEG), a member of the five egc superantigens. We found that SEA and SEG had similar superantigenic properties, as they induced CD69 expression on T lymphocytes and selective expansion of Vβ subpopulations. Contrary to SEG, however, SEA induced a strong proinflammatory/Th1 response, including TNF-α and MIP-1α production. These results suggest that the association of SEA with the severity of S. aureus septic shock, characterized by a deleterious, inflammatory cascade, may be explained partly by the specific proinflammatory properties of this superantigen.
5-Hydroxyeicosatetraenoic acid is a key intermediate of the arachidonate-dependent protective signaling in monocytes/macrophages exposed to peroxynitrite
Authors: Tommasini Ilaria , Guidarelli Andrea , Palomba Letizia , Cerioni Liana , Cantoni Orazio 
Published: August 2006

Abstract
Endogenous generation of arachidonic acid via selective activation of cytosolic phospholipase A2 has been implicated in the mechanism of monocytes/macrophage survival in the presence of peroxynitrite. In particular, the lipid messenger was shown to prevent the otherwise rapid onset of a mitochondrial permeability-transition (MPT)-dependent necrosis by causing the mitochondrial translocation of protein kinase Cα (PKCα) and the ensuing cytosolic accumulation of the Bcl-2-antagonist of cell death (Bad), an event promoting the anti-MPT function of Bcl-2 (or Bcl-XL). Here, we show that the effects on PKCα are not mediated directly by arachidonate but rather, by downstream products of the enzyme 5-lipoxygenase (5-LO). Peroxynitrite elicited the nuclear membrane translocation of 5-LO and enhanced its enzymatic activity via a mechanism sensitive to low concentrations of inhibitors of 5-LO or the 5-LO-activating protein, as well as to genetic depletion of the latter enzyme. Inhibition of 5-LO activity was invariably associated with the cytosolic localization of PKCα, the mitochondrial accumulation of Bad, and a rapid MPT-dependent necrosis. All these events were prevented by nanomolar concentrations of the 5-LO product 5-hydroxyeicosatetraenoic acid.
Bubbles and bypass: an update
Authors: Kurusz Mark , Butler Bruce D 
Published: August 2006

Bubbles in the bloodstream are not a normal condition -yet they remain a fact of cardiopulmonary bypass (CPB), having been extensively studied and documented since its inception some 50 years ago. While detectable levels of gaseous microemboli (GME) have decreased significantly in recent years and gross air embolism has been nearly eliminated due to increased awareness of etiologies and technological advances, methods of use of current perfusion systems continue to elicit concerns over how best to totally eliminate GME during open-heart procedures. A few studies have correlated adverse neurocognitive manifestations associated with excessive quantities of GME. Newer techniques currently in vogue, such as vacuum-assisted venous drainage, low-prime perfusion circuits, and carbon dioxide flooding of the operative field, have, in some instances, exacerbated the problem of gas embolism or engendered secondary complications in the safe conduct of CPB. Doppler monitoring (circuit or transcranial) primarily remains a research tool to detect GME emanating from the circuit or passing into the patients’ cerebral vasculature. Newer developments not yet widely available, such as multiple-frequency harmonics, may finally provide a tool to distinguish particulate microemboli from GME and further delineate the clinical significance of GME.
Paediatric CPB: Bypass in a High Risk Group
Authors: Jones TJ , Elliott MJ 
Published: August 2006

Children and particularly neonates present unique challenges during CPB. Patient age, size, underlying anatomy and surgical strategy influence the perfusion techniques and the construction of the CPB circuit. The normal changes in physiology in the first weeks of life impact upon surgical technique and outcome of repair. Limited surgical access necessitates alternative cannulation strategies. Deep hypothermia, low flow CPB and circulatory arrest are frequently used. An understanding of the related pathophysiology is therefore required to make the correct choices and to optimise patient outcome.
Would the addition of TENS to exercise training produce better physical performance outcomes in people with knee osteoarthritis than either intervention alone?
Authors: Cheing Gladys LY , Hui-Chan Christina WY 
Published: August 2006

Objective: To examine if the addition of transcutaneous electrical nerve stimulation (TENS) to exercise training would produce better physical outcomes than TENS or exercise alone in people with knee osteoarthritis. Design: Sixty-two subjects were randomly allocated to four groups. Interventions: Patients received either (1) TENS, (2) placebo stimulation, (3) exercise training, or (4) TENS and exercise training five days a week for four weeks. Main outcome measures: The isometric peak torque, spatiotemporal gait parameters and range of knee movement were assessed in treatment session1, session10 and session20 and the four-week follow-up. Results: By session20, the TENS and exercise group demonstrated an average of 26.6% cumulative gain in the knee extensor peak torque for the different knee positions (all p < 0.05). Although the between-group difference was short of being statistically significant, the gain found in the TENS and exercise group was greater than that found in the other three groups. The TENS and exercise group also tended to show greater cumulative increase in stride length (12.6%, p-0.006), walking cadence (9.3%, p-0.098) and gait velocity (22.4%, p-0.034) than the other groups. By session20, it was the only group that produced a significant increase in the range of knee motion during walking (12.0%,p-0.000). The TENS group and the exercise group both demonstrated some improvements in the above physical outcomes, but negligible change was found in the group receiving placebo stimulation (all p > 0.05). Conclusion: No significant difference was found among the four treatment protocols, but the addition of TENS to exercise training tended to produce the best overall improvement in physical outcomes in people with knee osteoarthritis.
Home training with and without additional group training in physically frail old people living at home: effect on health-related quality of life and ambulation
Authors: Helbostad Jorunn L , Sletvold Olav , Moe-Nilssen Rolf 
Published: August 2006

Objective: To test the effect of two exercise regimes on health-related quality of life (HRQoL) and ambulatory capacity. Design: Randomized controlled trial. Subjects: Seventy-seven community-dwelling physically frail people over 75 years of age (mean=81, SD=4.5). Interventions: Home training (HT, N =38) comprised twice daily functional balance and strength exercises and three group meetings. Combined training (CT, N =39) included group training twice weekly and the same home exercises. Interventions lasted 12 weeks. Physiotherapists ran both programmes. Home exercises were recorded daily. Main measures: HRQoL was assessed by SF-36, and ambulatory capacity by walking speed and frequency and duration of outdoor walks. Results: Following intervention, CT improved the SF-36 mental health index significantly more than HT (p =0.01). The SF-36 physical health index (p =0.002) and walking speed (p =0.02) demonstrated improvements, but no group differences. Six months after cessation of intervention there was still overall improvements on the mental health index (p =0.032), borderline overall improvements on the physical health index (p =0.057), higher weekly number of outdoor walks for the CT group than for the HT group (p =0.027) and an improved habitual walking speed in the CT group only (p =0.022). Conclusions: HT improved HRQoL and walking speed, but additional group training gave larger benefits on mental health. Group training away from home may be beneficial for mental health and ambulatory capacity.
A task-orientated intervention enhances walking distance and speed in the first year post stroke: a randomized controlled trial
Authors: Salbach N M , Mayo N E , Wood-Dauphinee S , Hanley J A , Richards C L , Côté R 
Published: August 2006

Objective: To evaluate the efficacy of a task-orientated intervention in enhancing competence in walking in people with stroke. Design: Two-centre observer-blinded stratified block-randomized controlled trial. Setting: General community. Subjects: Between May 2000 and February 2003, 91 individuals with a residual walking deficit within one year of a first or recurrent stroke consented to participate. Interventions: The experimental intervention comprised 10 functional tasks designed to strengthen the lower extremities and enhance walking balance, speed and distance. The control intervention involved the practice of upper extremity activities. Subjects in both groups attended sessions three times a week for six weeks. Main measures: Six-minute walk test (SMWT), 5-m walk (comfortable and maximum pace), Berg Balance Scale, timed ‘up and go’. Results: At baseline, subjects in the experimental ( n = 44) and control ( n = 47) groups walked an average distance of 209 m (SD = 126) and 204 m (SD = 131), respectively, on the SMWT. Mean improvements of 40 m (SD = 72), and 5 m (SD = 66) were observed following the experimental and control interventions, respectively. The between-group difference was 35 m (95% confidence interval (CI) 7, 64). Significant between-group effects of 0.21 m/s (95% CI 0.12, 0.30) and of 0.11 m/s (95% CI 0.03, 0.19) in maximum and comfortable walking speed, respectively, were observed. People with a mild, moderate or severe walking deficit at baseline improved an average of 36 (SD = 96), 55 (SD = 56) and 18 m (SD = 23), respectively, in SMWT performance following the experimental intervention. Conclusions: Study findings support the efficacy of a task-orientated intervention in enhancing walking distance and speed in the first year post stroke, particularly in people with moderate walking deficits.
The long-term outcomes from a randomized controlled trial of an educational–behavioural joint protection programme for people with rheumatoid arthritis
Authors: Hammond A , Freeman K 
Published: August 2006

Objective: To evaluate the long-term effects of joint protection on health status of people with early rheumatoid arthritis (RA). Design: A four-year follow-up of a randomized, controlled, assessor-blinded trial was conducted. Setting: Two rheumatology outpatient departments. Participants: People with rheumatoid arthritis less than five years since diagnosis. Interventions: Two 8-hour interventions were originally compared: a standard arthritis education programme, including 21/2 hours of joint protection based on typical UK occupational therapy practice (plus 51/2 hours on RA, exercise, pain management, diet and foot care); and a joint protection programme, using educational-behavioural training. Main measures: Adherence to joint protection, pain, hand pain on activity, Arthritis Impact Measurement Scales 2 and Arthritis Self-efficacy were recorded at 0 and 4 years. Results: Sixty-five people attended the joint protection and 62 the standard programmes. Groups at entry were similar in age (51 years; 49 years), disease duration (21 months: 17.5 months) and use of nonsteroidal anti-inflammatory and disease-modifying drugs. At four years, the joint protection group continued to have significantly better: joint protection adherence (p=0.001); early morning stiffness (p=0.01); AIMS2 activities of daily living (ADL) scores (p=0.04) compared with the standard group. The joint protection group also had significantly fewer hand deformities: metacarpophalangeal (MCP) (p=0.02) and wrist joints (p=0.04). Conclusion: Attending an educational=behavioural joint protection programme significantly improves joint protection adherence and maintains functional ability long term. This approach is more effective than standard methods of training and should be more widely adopted.
Can augmented physiotherapy input enhance recovery of mobility after stroke? A randomized controlled trial
Authors:   The Glasgow Augmented Physiotherapy Study (GAPS) group
Published: August 2006

Objective: To discover if the provision of additional inpatient physiotherapy after stroke speeds the recovery of mobility. Design: A multisite single-blind randomized controlled trial (RCT) comparing the effects of augmented physiotherapy input with normal input on the recovery of mobility after stroke. Setting: Three rehabilitation hospitals in North Glasgow, Scotland. Subjects: Patients admitted to hospital with a clinical diagnosis of stroke, who were able to tolerate and benefit from mobility rehabilitation. Intervention: We aimed to provide double the amount of physiotherapy to the augmented group. Main measures: Primary outcomes were mobility milestones (ability to stand, step and walk), Rivermead Mobility Index (RMI) and walking speed. Results: Seventy patients were recruited. The augmented therapy group received more direct contact with a physiotherapist (62 versus 35 minutes per weekday) and were more active (8.0% versus 4.8% time standing or walking) than normal therapy controls. The augmented group tended to achieve independent walking earlier (hazard ratio 1.48, 95% confidence interval 0.90–2.43; p=0.12) and had higher Rivermead Mobility Index scores at three months (mean difference 1.6; 0.1 to 3.3; p=0.068) but these differences did not reach statistical significance. There was no significant difference in any other outcome. Conclusions: A modest augmented physiotherapy programme resulted in patients having more direct physiotherapy time and being more active. The inability to show statistically significant changes in outcome measures could indicate either that this intervention is ineffective or that our study could not detect modest changes.
Does motor imagery training improve hand function in chronic stroke patients? A pilot study
Authors: Dijkerman H C , Ietswaart M , Johnston M , MacWalter R S 
Published: August 2006

Objective: To assess the efficacy of motor imagery training for arm function in chronic stroke patients. The relation between mental processes such as attentional and perceived personal control over recovery, and motor imagery was additionally investigated. Design and subjects: Twenty patients with long-term motor impairments (mean two years post stroke), were assessed before and after four weeks of training. Ten patients mentally rehearsed movements with their affected arm. Their recovery was compared with patients who performed nonmotor imagery (n =5), or who were not engaged in mental rehearsal (n =5). Setting: Patients were recruited from the stroke database of Ninewells Hospital, Dundee. Assessment and training were performed at the patients' home. Interventions: The motor imagery group was asked to practise daily imagining moving tokens with their affected arm. The nonmotor imagery group rehearsed visual imagery of previously seen pictures. All patients practised physically moving the tokens. Main measures: The following variables were assessed before and after training: motor function (training task, pegboard and dynamometer), perceived locus of control, attention control and ADL independence. Results: All patient groups improved on all motor tasks except the dynamometer. Improvement was greater for the motor imagery group on the training task only (average of 14% versus 6%). No effect of motor imagery training was found on perceived or attentional control. Conclusions: Motor imagery training without supervision at home may improve performance on the trained task only. The relation between movement imagery, attention and perceived personal control over recovery remained unclear.
The effect of an ankle-foot orthosis on walking ability in chronic stroke patients: a randomized controlled trial
Authors: de Wit D CM , Buurke J H , Nijlant J MM , IJzerman M J , Hermens H J 
Published: August 2006

Objective: Regaining walking ability is a major goal during the rehabilitation of stroke patients. To support this process an ankle-foot orthosis (AFO) is often prescribed. The aim of this study is to investigate the effect of an AFO on walking ability in chronic stroke patients. Design: Cross-over design with randomization for the interventions. Methods: Twenty chronic stroke patients, wearing an AFO for at least six months, were included. Walking ability was operationalized as comfortable walking speed, scores on the timed up and go (TUG) test and stairs test. Patients were measured with and without their AFO, the sequence of which was randomized. Additionally, subjective impressions of self-confidence and difficulty of the tasks were scored. Clinically relevant differences based on literature were defined for walking speed (20 cm/s), the TUG test (10 s). Gathered data were statistically analysed using a paired t-test. Results: The mean difference in favour of the AFO in walking speed was 4.8 cm/s (95% CI 0.85–8.7), in the TUG test 3.6 s (95% CI 2.4 4.8) and in the stairs test 8.6 s (95% CI 3.1 –14.1). Sixty-five per cent of the patients experienced less difficulty and 70% of the patients felt more self-confident while wearing the AFO. Conclusions: The effect of an AFO on walking ability is statistically significant, but compared with the a priori defined differences it is too small to be clinically relevant. The effect on self-confidence suggests that other factors might play an important role in the motivation to use an AFO.