DCP1 forms asymmetric trimers to assemble into active mRNA decapping complexes in metazoa

DCP1 stimulates the decapping enzyme DCP2, which removes the mRNA 5′ cap structure committing mRNAs to degradation. In multicellular eukaryotes, DCP1-DCP2 interaction is stabilized by additional proteins, including EDC4. However, most information on DCP2 activation stems from studies in S. cerevisiae, which lacks EDC4. Furthermore, DCP1 orthologs from multicellular eukaryotes have a C-terminal extension, absent in fungi. Here, we show that in metazoa, a conserved DCP1 C-terminal domain drives DCP1 trimerization. Crystal structures of the DCP1-trimerization domain reveal an antiparallel assembly comprised of three kinked α-helices. Trimerization is required for DCP1 to be incorporated into active decapping complexes and for efficient mRNA decapping in vivo. Our results reveal an unexpected connectivity and complexity of the mRNA decapping network in multicellular eukaryotes, which likely enhances opportunities for regulating mRNA degradation.     

Implant-supported fixed cantilever prosthesis in partially edentulous jaws: a cohort prospective study

Background: Reconstructive procedures present a higher rate of biological costs due to the necessity of bone harvest and grafts, use of semipermeable barriers etc. On the hand, implant supported cantilever prostheses could allow a simpler rehabilitation procedure. Aims: The aim of the present study was to assess the clinical outcome of patients treated with implant‐supported fixed partial dentures (FPD) with cantilever after a mean follow‐up time of 8 years. Material and methods: The study included 45 consecutive partially edentulous patients treated between January 1994 and August 2006 with 59 partial cantilever fixed prostheses supported by 116 ITI^® implants. The primary outcome variable considered was the presence of complications at the subject and bridge level; the secondary outcome variable was marginal bone loss (MBL). The frequency of complications was analyzed according to cantilever location and opposite dentition and tested by Fisher's exact test. A multilevel regression model was constructed to analyze the factors influencing MBL with three levels: subject as the highest, and then implant and site. During the follow‐up period, 11 implants showed a bone loss exceeding the limit for success, out of which two implants showed an infection of the peri‐implant tissue. Results: After an average observation of 8.2 years of cantilever prostheses loading, the implant success and survival rates were 90.5% and 100%, respectively. Besides, the prosthetic success and survival rate were 57.7% and 100%, respectively. Discussion: None of the predictors included in the multilevel model presented a significant impact on the bone loss between baseline and the follow‐up examination. Conclusions: The authors concluded that the prognosis of implant‐supported FPDs and marginal bone loss at implants were not influenced by the position or the length of the cantilever, the location of the bridge and type of opposite dentition. Implant‐supported fixed cantilever prosthesis can be considered a suitable treatment choice.     

The effect of spatial layout on motion segmentation

We present a series of experiments exploring the effect of the stimulus spatial configuration on speed discrimination and two different types of segmentation, for random dot patterns. In the first experiment, we find that parsing the image produces a decrease of speed discrimination thresholds such as was first shown by Verghese and Stone [Verghese, P., & Stone, L. (1997). Spatial layout affects speed discrimination threshold. Vision Research, 37(4), 397-406; Verghese, P., & Stone, L. S. (1996). Perceived visual speed constrained by image segmentation. Nature, 381, 161-163] for sinusoidal gratings. In the second experiment, we study how the spatial configuration affects the ability of a subject in localizing an illusory contour defined by two surfaces with different speeds. Results show that the speed difference necessary to localize the contour decreases as the stimulus patches are separated. The third experiment involves transparency. Our results show a little or null effect for this condition. We explain the first and second experiment in the framework of the model of Bravo and Watamaniuk [Bravo, M., & Watamaniuk, S. (1995). Evidence for two speed signals: a coarse local signal for segregation and a precise global signal for discrimination. Vision Research, 35(12), 1691-1697] who proposed that motion computation consists in, at least, two stages: a first computation of coarse local speeds followed by an integration stage. We propose that the more precise estimate of speed obtained from the integration stage is used to produce a new refined segmentation of the image perhaps, through a feedback loop. Our data suggest that this third stage would not apply to the processing of transparency.     

Effects of treadmill training on walking economy in Parkinson’s disease: a pilot study

Gait disturbances are frequent in Parkinson’s disease (PD) and are associated with increased energy expenditure during walking. This study evaluated whether the effects of treadmill training are associated with an improvement of walking economy. Ten patients with idiopathic PD underwent treadmill training (30 min, three times a week for 4 weeks). Walking performance (Τimed Up and Go, 6-min and 10-m walking tests) and metabolic function (oxygen uptake, heart and respiratory rate) were evaluated before training, at the end of treatment and after 30 days with two different graded exercises (treadmill and cycloergometer). Training significantly improved walking performance. Oxygen uptake, and heart and respiratory rates were significantly decreased only during graded exercise on the treadmill, but not on the cycloergometer. Treadmill training reduces energy expenditure during walking in PD, but the improvements of metabolic walking economy are associated with the specifically trained motor activity.     

Eyelid fluttering, typical EEG pattern, and impaired intellectual function: A homogeneous epileptic condition among the patients presenting with eyelid myoclonia

Purpose:   This retrospective study aims to review the electroclinical features of patients presenting with eyelid myoclonia (EM) with and without absences.
Methods:   The Italian chapter of the International League Against Epilepsy (ILAE) has been conducting an electroclinical study of patients with EM. Among these, we searched for and selected the patients presenting with both impairment of intellectual functions and a peculiar ictal electroencephalography (EEG) pattern, that is, a discharge of fast generalized polyspikes/polyspikes and waves.
Results:   We found 18 patients matching this electroclinical picture. All the patients were photosensitive. All of them had associated generalized, mostly nocturnal, tonic–clonic seizures. During the evolution, 13 patients presented episodes of EM status. Despite adequate antiepileptic treatment, the patients remained drug resistant for many years or throughout the evolution. The degree of impairment of intellectual functions varied from borderline level to moderate mental retardation.
Discussion:   The patients we described herein can be considered a homogeneous group in the more heterogeneous group of patients presenting with EM. Further clinical and, more probably, genetic studies will clarify whether this condition could be considered a specific and homogeneous condition in the more heterogeneous group of patients presenting with EM.     

A new model of epidermal culture for the surgical treatment of vitiligo

Background Vitiligo can be successfully treated with grafts of autologous cultured epidermal cells. Objective To evaluate the efficacy of autologous grafting of epidermal cells, cultured by an original method, in the treatment of localized vitiligo refractory to other therapies. Methods Autologous normally pigmented skin was used to culture keratinocytes and melanocytes on a supporting layer of biomaterial (Laserskin), which was grafted directly onto achromatic skin after de-epithelialization with liquid carbon dioxide. The percentage area of repigmentation was calculated by image analysis. Results Initial repigmentation of the treated areas was observed 1 month after treatment. Repigmentation continued to increase for 3 months after grafting. Follow-up at 3, 6, 12, and 18 months showed almost complete repigmentation in six out of 11 cases. In four other patients, 40–71% of the grafted achromatic area was repigmented. In one patient, repigmentation was impeded by sepsis. Conclusions The method was found to be effective in the treatment of localized vitiligo refractory to other treatments. The therapeutic procedure was simple, reproducible, and easy to use.     

Microsatellite instability in breast cancer

Background: Microsatellites are short repetitive nucleotide sequences that, through mutation, can undergo either expansion or contraction. This novel mutational mechanism known as microsatellite instability may play a role in carcinogenesis. We investigated the incidence of microsatellite instability in a series of primary breast carcinoma surgical specimens. Methods: Using polymerase chain reaction techniques followed by polyacrylamide/urea gel electrophoresis, we analyzed 46 pairs of normal and primary breast tumor samples at seven different microsatellite loci, five of which were located on chromosome 17. Results: Thirteen of our 46 tumors (28.2%) demonstrated microsatellite instability. Five tumors (10.8%) were unstable at two or more loci, and of those, four (8.7%) were unstable at different loci on different chromosomes. An additional five tumors demonstrated loss of heterozygosity alone when compared with their normal counterparts. Conclusions: These findings indicate that microsatellite instability is present in primary breast cancer populations and, although the mechanism of action has yet to be elucidated, may play a role in breast carcinogenesis.Presented at the 49th Annual Cancer Symposium of The Society of Surgical Oncology, Atlanta, Georgia, March 21–24, 1996.     

A pseudo-outbreak of vancomycin-resistant Enterococcus faecium.

Five VRE isolates were reported from sterile samples. No infections were diagnosed among the patients, who were on different wards. PFGE showed that all five isolates were clonal. All samples were manipulated by the same worker, but the source could not be found. Contamination was probably related to manipulation of a source specimen in the laboratory.     

Home Infusion Therapies for Obstetric Patients

This article focuses on current indications for home intravenous therapy for the high-risk obstetric patient. Therapeutic indications and clinical care for obstetric patients in need of hydration/total parenteral nutrition, heparin infusion, terbutaline pump, and antibiotic therapies are presented.