Pruning an axon piece by piece: a new mode of synapse elimination

The process by which excess axons are pruned during development has remained unclear. In this issue of Neuron, Bishop et al. use time-lapse imaging and serial electron microscopy of developing neuromuscular junctions to describe a novel cellular mechanism in which retracting axon branches shed fragments rich in normal synaptic organelles. These "axosomes" are engulfed by adjacent Schwann cells and may be assimilated into the glial cytoplasm. Shedding of axosomes and glial engulfment may represent a widespread mechanism of synapse elimination.     

Free proximal gracilis muscle and its skin paddle compound flap transplantation for complex facial paralysis

Gracilis functioning free-muscle transplantation for the correction of pure facial paralysis has been a preferred method used by many reconstructive microsurgeons. However, for complex facial paralysis, the deficits include facial paralysis along with soft-tissue, mucosa, and/or skin defects. No adequate solution has been proposed. Treatment requests in those patients are not only for facial reanimation but also for correction of the defects. Of 161 patients with facial paralysis treated with gracilis functioning free-muscle transplantation from 1986 to 2002, eight patients (5 percent) presented with complex deficits requiring not only facial reanimation but also aesthetic correction of tissue defects. The tissue defects included an intraoral defect created following contracture release (one patient), infra-auricular radiation dermatitis with contour depression (one patient), temporal depression following a temporalis muscle-fascia transfer (one patient), ear deformity (two patients), and infra-auricular atrophic tissue with contour depression (three patients). A compound flap, consisting of a gracilis muscle with its overlying skin paddle separated into two components, was transferred for simultaneous correction of both problems. The blood supply to the gracilis and to the skin paddle originated from the same source vessel and therefore required the anastomosis of only one set of vessels. The versatility of this compound flap allows for a wide arc of rotation of the skin paddle around the muscle. All flaps were transferred successfully without complications. Satisfactory results of facial reanimation were recorded in five patients after all stages were completed. The remaining three patients are undergoing physical therapy and waiting for revision of the skin paddle.     

Free-style free flaps

Free-tissue transfer has become the accepted standard for reconstruction of complex defects. With the growth of this field, anatomic studies and clinical work have added many flaps to the armamentarium of the microvascular surgeon. Further advancements and experience with techniques of perforator flap surgery have allowed for the harvest of flaps in a free-style manner, where a flap is harvested based only on the preoperative knowledge of Doppler signals present in a specific region. Between June of 2002 and September of 2003, 13 free-style free flaps were harvested from the region of the thigh. All patients presented with an oral or pharyngeal cancer and underwent resection and immediate reconstruction of these flaps. All flaps were cutaneous and were harvested in a suprafascial plane. The average size of the flaps was 108 cm2 (range, 36 to 187 cm2), and the average length of the vascular pedicle was 10 cm (range, 9 to 12 cm). All flaps were successful in achieving wound coverage and functional outcomes without any vascular compromise necessitating re-exploration. Free-style free flaps have become a clinical reality. The concepts and techniques used to harvest a free-style free flap will aid in dealing with anatomic variations that are encountered during conventional flap harvest. Future trends in flap selection will focus mainly on choosing tissue with appropriate texture, thickness, and pliability to match requirements at the recipient site while minimizing donor-site morbidity.     

Comparison of the radial forearm flap and the thinned anterolateral thigh cutaneous flap for reconstruction of tongue defects: an evaluation of donor-site morbidity

The radial forearm flap is commonly used for reconstruction of tongue defects following tumor extirpation. This flap is easy to harvest and offers thin tissue with large-caliber vessels. However, its use leaves behind a conspicuous aesthetic deformity in the forearm and requires the sacrifice of a major artery of that limb, the radial artery. The anterolateral thigh cutaneous flap has found clinical applications in the reconstruction of soft-tissue defects requiring thin tissue. More recently, in a thinned form, the anterolateral thigh flap has been used for reconstructing defects of the tongue with functional results equivalent to that of the radial forearm flap. For the reconstruction of tongue defects, these two flaps could provide similar soft-tissue coverage, but they seem to result in different donor-site appearances. The donor site is closed primarily, leaving only a linear scar that is inconspicuous with normal clothing, and no functional deficit is left behind in the thigh. Thus, for the supply of flaps for tongue defects, a comparison between the radial forearm flap and the anterolateral thigh flap donor sites is provided in this study. Between December of 2000 and August of 2002, 41 patients who underwent reconstruction of defects of the tongue using either a radial forearm flap or an anterolateral thigh flap were evaluated. The focus was on the evaluation of the functional and aesthetic outcome of the donor site after harvesting these flaps for the purpose of reconstructing either total or partial tongue defects. Finally, a comparison was performed between the donor sites of the two flaps. The disadvantages of the radial forearm flap include the conspicuous unattractive scar in the forearm region, pain, numbness, and the sacrifice of a major artery of the limb. In some patients, the donor-site scar of the forearm acted as a social stigma, preventing these patients from leading a normal life. In contrast, the anterolateral thigh cutaneous flap, after thinning, achieved the same results in reconstructing defects of the tongue without the associated donor-site morbidity. Most importantly, the donor site in the thigh could be closed primarily in almost all patients without any functional deficit. The thinned anterolateral thigh cutaneous flap is a viable substitute for the radial forearm flap when reconstructing defects of the tongue. The results achieved are similar to those of the radial forearm flap, and the donor-site morbidity is significantly decreased.     

Strategies for a successful corrective Asian blepharoplasty after previously failed revisions

Asian blepharoplasty, although a common procedure, has a relatively high rate of complications. Subtle imperfections and more serious iatrogenic complications often require immediate attention by the aesthetic surgeon. After attempted correction of the deformities, residual problems or new ones can arise. Blepharoptosis, supratarsal depression, an excessively high or low crease, a short or discontinuous crease, multiple creases, and asymmetric creases are the most commonly encountered complications that require special attention in this group, which has already undergone more than one surgical procedure. Between January of 1996 and December of 2002, 168 Asian blepharoplasty revisions were performed by one surgeon (S. H.-T. Chen); of these, 36 patients (21 percent) had previously undergone failed revisions. This subgroup of patients consisted of six with blepharoptosis, six with asymmetrical eyelid creases, three with supratarsal depressions, three with high creases, two with short creases, and 16 with combinations of these deformities. The results were graded as excellent, good, fair, or poor, based on the symmetry of the eyelids, palpebral fissures, crease heights, lengths, shapes, eyelid fullness, and overall aesthetics of the final outcome. A survey was performed of patient and surgeon satisfaction and factored into the grading system. With an average follow-up period of 16 months (6 to 60 months), 22 patients (61 percent) were found to have excellent results, 10 (28 percent) had good results, two (5.6 percent) had fair results, and two (5.6 percent) had poor results. Corrective procedures after failed revision Asian blepharoplasty require special strategic considerations because of the presence of extensive scarring and inadequate skin, muscle, and preaponeurotic fat and because of the occasional presence of dehiscence of the levator aponeurosis. By using careful preoperative evaluation, accurate measurements, precise preoperative planning, intraoperative fat repositioning or grafting, skin excision or redraping, and proper placement of anchoring sutures, successful outcomes can be achieved. The authors evaluate the outcomes and detail the surgical procedures that were used to achieve successful outcomes in this particularly challenging group of patients.     

The “averaging fallacy” and the levels of selection

This paper compares two well-known arguments in the units of selection literature, one due to , the other due to . Both arguments concern the legitimacy of averaging fitness values across contexts and making inferences about the level of selection on that basis. The first three sections of the paper shows that the two arguments are incompatible if taken at face value, their apparent similarity notwithstanding. If we accept Sober and Lewontin's criterion for when averaging genic fitnesses across diploid genotypes is illegitmate, we cannot accept Sober and Wilson's criterion for when averaging individual fitnesses across groups is illegitimate, and vice versa. The final section suggests a possible way of reconciling the two arguments, by invoking an ambiguity in the concept of genic selection.     

Synthesis and evaluation of 4-triazolylflavans as new aromatase inhibitors

Aromatase is a target of pharmacological interest for the treatment of estrogen-dependent cancers. Azole derivatives such as letrozole or anastrozole have been developed for aromatase inhibition and are used for the treatment of breast tumors. In this paper, four 4-triazolylflavans were synthesized and were found to exhibit moderate to high inhibitory activity against aromatase.     

The incidence of Helicobacter pylori acquisition in children of a Canadian First Nations community and the potential for parent-to-child transmission

BACKGROUND AND AIMS: We have previously reported that Wasagamack, a Canadian First Nations community has a seroprevalence rate of Helicobacter pylori of 95% and a prevalence rate among children aged 0-12 years as measured by stool antigen testing of 56%. We aimed to determine the rate of infection acquisition and possible modes of transmission of childhood Helicobacter pylori infection in this Canadian First Nations community. METHODS: Children who were previously negative for H. pylori by stool antigen testing in August 1999 were eligible for enrollment in August 2000; 50 (77%) eligible children underwent stool collection. H. pylori stool antigen status was tested using the Premier Platinum HpSA test. Drinking water samples, maternal saliva, breast milk, local berries and flies were tested by three complementary H. pylori-specific PCR assays. Soothers or bottle nipples, collected from 16 children whose H. pylori stool antigen status was determined, were bathed in sterile water and this water was tested by PCR. RESULTS: Stool was positive for H. pylori in 16% (8/ 50) of children retested. Five had no other siblings infected and three had infected siblings. The mothers of all children infected were positive for H. pylori. The median age of newly infected children was 6 years (range 1-13 years). By PCR, 78% (18/23) mothers' saliva samples, 69% (11/16) soother water samples and 9% (1/11) water samples from infected homes tested positive. All of 24 sequenced PCR-produced DNA fragments from samples showed 99% homology with that from ATCC type strain H. pylori. CONCLUSIONS: The rate of childhood H. pylori acquisition was 16% over 1 year, and was not dependent on number of siblings infected. The finding of homologous H. pylori DNA in saliva and in soother water suggests the possibility of human to human transmission, particularly via an oral-oral route. Thus, there is the potential for further investigations in this population and other endemic communities that are directed at prevention of infection transmission via this modality.     

CoPS: Comprehensive Peptide Signature database

We present the development of a Comprehensive database of 12 076 invariant Peptide Signatures (CoPS) derived from 52 bacterial genomes with a minimum occurrence in at least seven organisms. These peptides were observed in functionally similar proteins and are distributed over nearly 1250 different functional proteins. The database provides function, structure and occurrence in biochemical pathways of the proteins containing these signature peptides. It houses additional information on the signature peptides, such as identical match in other motif/pattern (e.g. PROSITE, BLOCKS, PRINTS and Pfam) databases and the database of interacting proteins, human proteome and mutation effect on these signature peptides. There is a wide applicability of this database in the identification of critical functional residues in proteins. The database also facilitates the identification of folding nucleus/structural determinants in proteins and functional assignment to yet unknown proteins. We demonstrate functional assignment to 2605 hypothetical proteins in bacterial genomes and 112 unknown proteins in human using this database. AVAILABILITY: The database can be freely accessed through the following URL: http://203.195.151.46/copsv2/index.html or http://203.90.127.70/copsv2/index.html