Single-stage, autologous breast restoration

The skin-sparing mastectomy, when performed with immediate reconstruction, is a major advance in breast reconstruction. Traditionally, reconstruction of the nipple-areola complex is performed as a subsequent procedure. In this study, 17 patients (mean age, 43 years; range, 35 to 53 years) underwent one-stage breast and nipple-areola reconstruction over a 21-month period. In all cases of breast reconstruction, a buried transverse rectus abdominis musculocutaneous (TRAM) flap was used, and all patients had a simultaneous nipple-areola complex reconstruction performed. Nine patients had a Wise keyhole pattern used and contralateral reduction performed. Four patients retained all their breast skin, and a TRAM skin island was used in another four. It has recently been shown that patients with early-stage breast cancer and peripherally sited tumors have a very low risk of nipple-areola involvement. In 10 patients with early disease and peripheral tumors, the areola was retained (as a thin full-thickness graft), but more recently, in three patients with early-stage disease, the entire nipple-areola complex was used as a thin full-thickness graft. The thin full-thickness skin graft is removed from the breast in an apple-coring fashion, so that most of the ducts are retained as part of the mastectomy specimen. (There was histological confirmation of absence of tumor in the nipples of these patients.)One-stage autologous reconstruction should be considered for all patients undergoing immediate breast reconstruction. In patients with early-stage disease and peripheral tumors, the nipple-areola complex may be retained through the use of a thin full-thickness graft that is applied to a deepithelialized CV flap on the TRAM flap. This allows the best method of nipple-areola complex reconstruction: by retaining the original breast envelope, the color match and texture in the reconstruction are ideal. Patient satisfaction in this study was high. Necrosis of the mastectomy flaps impaired the cosmetic results in some patients. A large multicenter study is required to confirm the effectiveness of this procedure.     

Baseline Assessment of Mesophotic Reefs of the Vitória-Trindade Seamount Chain Based on Water Quality,Microbial Diversity,Benthic Cover and Fish Biomass Data

Seamounts are considered important sources of biodiversity and minerals. However, their biodiversity and health status are not well understood; therefore, potential conservation problems are unknown. The mesophotic reefs of the Vitória-Trindade Seamount Chain (VTC) were investigated via benthic community and fish surveys, metagenomic and water chemistry analyses, and water microbial abundance estimations. The VTC is a mosaic of reef systems and includes fleshy algae dominated rhodolith beds, crustose coralline algae (CCA) reefs, and turf algae dominated rocky reefs of varying health levels. Macro-carnivores and larger fish presented higher biomass at the CCA reefs (4.4 kg per frame) than in the rhodolith beds and rocky reefs (0.0 to 0.1 kg per frame). A larger number of metagenomic sequences identified as primary producers (e.g., Chlorophyta and Streptophyta) were found at the CCA reefs. However, the rocky reefs contained more diseased corals (>90%) than the CCA reefs (~40%) and rhodolith beds (~10%). Metagenomic analyses indicated a heterotrophic and fast-growing microbiome in rocky reef corals that may possibly lead to unhealthy conditions possibly enhanced by environmental features (e.g. light stress and high loads of labile dissolved organic carbon). VTC mounts represent important hotspots of biodiversity that deserve further conservation actions.     

Effect of testosterone and bovine follicular fluid on concentrations of luteinizing hormone and follicle-stimulating hormone in plasma of castrated rams that are homozygous carriers or non-carriers of the Booroola fecundity gene.

Castrated adult FecBFecB and Fec+Fec+ Booroola rams were injected with charcoal-treated bovine follicular fluid (bFF) (a source of inhibin-like activity) or given testosterone implants to examine whether the fecundity gene (FecB) influences sensitivity to negative feedback hormones in males. Mean concentrations of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) did not differ between genotypes before treatment. In Expt 1, injections of 5 ml bFF, but not of 1 ml (each given four times at intervals of 8 h), significantly (P < 0.05) depressed concentrations of LH and FSH, but there was no effect of genotype. After treatment, gonadotrophin concentrations returned to pretreatment values and for 2-2.5 days scaled (divided by pretreatment mean) LH values (235 +/- 49 for FecBFecB and 96 +/- 26% for Fec+Fec+ rams; P < 0.05) and scaled FSH values (106 +/- 5 for FecBFecB and 85 +/- 5% for Fec+Fec+ rams; P < 0.05) were significantly higher in FecBFecB than in Fec+Fec+ rams in the group that received 5 ml bFF. Irrespective of genotype, treatment with 5 ml bFF did not reduce mean FSH to concentrations observed in testis-intact rams. In Expt 2, Silastic envelopes were implanted subdermally to give physiological or supraphysiological circulating concentrations of testosterone. Both doses significantly reduced scaled LH values in a biphasic manner, such that there was an initial suppression followed by a short-lived increase. During the initial period of suppression in the lower dose group, mean scaled LH values were significantly higher in FecBFecB than in Fec+Fec+ rams (48.3 +/- 7.5 versus 23.1 +/- 5.5%; P < 0.05). Low doses of testosterone decreased LH pulse frequency in both genotypes but decreased (P < 0.05) pulse amplitude and mean concentrations in the Fec+Fec+ animals only. In nonimplanted control rams, mean LH concentrations (in samples taken every 10 min for 12 h) were significantly lower in FecBFecB than in Fec+Fec+ rams (0.6 +/- 0.2 versus 1.3 +/- 0.1 ng ml-1; P < 0.05). The mean FSH response to testosterone was not related to genotype. These data suggest that expression of the FecB gene results in an altered sensitivity of the pituitary gland to changes in negative feedback from testicular hormones and that, irrespective of genotype, neither testosterone nor inhibin-like activity alone can fully control FSH secretion in castrated rams.     

Hybridization and speciation

Hybridization has many and varied impacts on the process of speciation. Hybridization may slow or reverse differentiation by allowing gene flow and recombination. It may accelerate speciation via adaptive introgression or cause near‐instantaneous speciation by allopolyploidization. It may have multiple effects at different stages and in different spatial contexts within a single speciation event. We offer a perspective on the context and evolutionary significance of hybridization during speciation, highlighting issues of current interest and debate. In secondary contact zones, it is uncertain if barriers to gene flow will be strengthened or broken down due to recombination and gene flow. Theory and empirical evidence suggest the latter is more likely, except within and around strongly selected genomic regions. Hybridization may contribute to speciation through the formation of new hybrid taxa, whereas introgression of a few loci may promote adaptive divergence and so facilitate speciation. Gene regulatory networks, epigenetic effects and the evolution of selfish genetic material in the genome suggest that the Dobzhansky–Muller model of hybrid incompatibilities requires a broader interpretation. Finally, although the incidence of reinforcement remains uncertain, this and other interactions in areas of sympatry may have knock‐on effects on speciation both within and outside regions of hybridization.     

Inhibition of Taq DNA polymerase by seaweed extracts from British Columbia, Canada and Korea

Fifty-nine species of marine macrophytes from the coasts of British Columbia, Canada and Korea have been screened for the presence of PCR inhibitors, namely inhibitors of Taq DNA polymerase. Eleven of the species displayed some inhibitor activity. At the concentration of 5 μg of methanol extract in 25μL reaction mixture of PCR containing 1.5 unit of Taq DNA polymerase, one (Ulva sp.) of 8 Chlorophyta, eight (Colpomenia bullosa, Ecklonia cava, Endarachne binghamiae, Fucus distichus, Hizikia fusiformis, Sargassum confusum, Sargassum sagamianum, and Sargassum thunbergii) of 28 Phaeophyta, and one (Symphyocladia latiuscula) of 34 Rhodophyta showed inhibition in PCR amplification. In the case of the water extract, two (Cladophora columbiana, Ulva sp.) Chlorophyta, seven (Endarachne binghamiae, Fucus distichus, Hizikia fusiformis, Sargassum confusum, Sargassum sagamianum, Sargassum horneri, Scytosiphon dotyi) Phaeophyta, no Rhodophyta and one (Phyllospadix scouleri) seagrass showed inhibition in PCR amplification. the methanol fraction of Sargassum confusum and the water fraction of Fucus gardneri (mid–intertidal) have been found to inhibit PCR at level as low as 0.5 μg in 25μL of PCR reaction mixture. This revised version was published online in August 2006 with corrections to the Cover Date.     

Phenotypic profiling of mGlu7 knockout mice reveals new implications for neurodevelopmental disorders

Neurodevelopmental disorders are characterized by deficits in communication, cognition, attention, social behavior and/or motor control. Previous studies have pointed to the involvement of genes that regulate synaptic structure and function in the pathogenesis of these disorders. One such gene, GRM7, encodes the metabotropic glutamate receptor 7 (mGlu₇), a G protein‐coupled receptor that regulates presynaptic neurotransmitter release. Mutations and polymorphisms in GRM7 have been associated with neurodevelopmental disorders in clinical populations; however, limited preclinical studies have evaluated mGlu₇ in the context of this specific disease class. Here, we show that the absence of mGlu₇ in mice is sufficient to alter phenotypes within the domains of social behavior, associative learning, motor function, epilepsy and sleep. Moreover, Grm7 knockout mice exhibit an attenuated response to amphetamine. These findings provide rationale for further investigation of mGlu₇ as a potential therapeutic target for neurodevelopmental disorders such as idiopathic autism, attention deficit hyperactivity disorder and Rett syndrome.     

Manipulation of host-resource dynamics impacts transmission of trophic parasites

Many complex life cycle parasites rely on predator–prey interactions for transmission, whereby definitive hosts become infected via the consumption of an infected intermediate host. As such, these trophic parasites are embedded in the larger community food web. We postulated that exposure to infection and, hence, parasite transmission are inherently linked to host foraging ecology, and that perturbation of the host-resource dynamic will impact parasite transmission dynamics. We employed a field manipulation experiment in which natural populations of the eastern chipmunk (Tamias striatus) were provisioned with a readily available food resource in clumped or uniform spatial distributions. Using replicated longitudinal capture-mark-recapture techniques, replicated supplemented and unsupplemented control sites were monitored before and after treatment for changes in infection levels with three gastro-intestinal helminth parasites. We predicted that definitive hosts subject to food supplementation would experience lower rates of exposure to infective intermediate hosts, presumably because they shifted their diet away from the intermediate host towards the more readily available resource (sunflower seeds). As predicted, prevalence of infection by the trophically transmitted parasite decreased in response to supplemental food treatment, but no such change in infection prevalence was detected for the two directly transmitted parasites in the system. The fact that food supplementation only had an impact on the transmission of the trophically transmitted parasite, and not the directly transmitted parasites, supports our hypothesis that host foraging ecology directly affects exposure to parasites that rely on the ingestion of intermediate hosts for transmission. We concluded that the relative availability of different food resources has important consequences for the transmission of parasites and, more specifically, parasites that are embedded in the food web. The broader implications of these findings for food web dynamics and disease ecology are discussed.     

The Supplementary Motor Area Exerts a Tonic Excitatory Influence on Corticospinal Projections to Phrenic Motoneurons in Awake Humans

Introduction

In humans, cortical mechanisms can interfere with autonomic breathing. Respiratory-related activation of the supplementary motor area (SMA) has been documented during voluntary breathing and in response to inspiratory constraints. The SMA could therefore participate in the increased resting state of the respiratory motor system during wake (i.e. "wakefulness drive to breathe").

Methods

The SMA was conditioned by continuous theta burst magnetic stimulation (cTBS, inhibitory) and 5 Hz conventional rTMS (5 Hz, excitatory). The ensuing effects were described in terms of the diaphragm motor evoked response (DiMEPs) to single-pulse transcranial magnetic stimulation over the motor cortex. DiMEPs were recorded at baseline, and at 3 time-points ("post1", "post2", "post3") up to 15 minutes following conditioning of the SMA.

Results

cTBS reduced the amplitude of DiMEPs from 327.5±159.8 µV at baseline to 243.3±118.7 µV, 217.8±102.9 µV and 240.6±123.9 µV at post 1, post 2 and post 3, respectively (F = 6.341, p = 0.002). 5 Hz conditioning increased the amplitude of DiMEPs from 184.7±96.5 µV at baseline to 270.7±135.4 µV at post 3 (F = 4.844, p = 0.009).

Conclusions

The corticospinal pathway to the diaphragm can be modulated in both directions by conditioning the SMA. This suggests that the baseline respiratory activity of the SMA represents an equipoise from which it is possible to move in either direction. The resting corticofugal outflow from the SMA to phrenic motoneurones that this study evidences could putatively contribute to the wakefulness drive to breathe.     

Propagation of protein glycation damage involves modification of tryptophan residues via reactive oxygen species: inhibition by pyridoxamine

Nonenzymatic modification of proteins is one of the key pathogenic factors in diabetic complications. Uncovering the mechanisms of protein damage caused by glucose is fundamental to understanding this pathogenesis and in the development of new therapies. We investigated whether the mechanism involving reactive oxygen species can propagate protein damage in glycation reactions beyond the classical modifications of lysine and arginine residues. We have demonstrated that glucose can cause specific oxidative modification of tryptophan residues in lysozyme and inhibit lysozyme activity. Furthermore, modification of tryptophan residues was also induced by purified albumin-Amadori, a ribose-derived model glycation intermediate. The AGE inhibitor pyridoxamine (PM) prevented the tryptophan modification, whereas another AGE inhibitor and strong carbonyl scavenger, aminoguanidine, was ineffective. PM specifically inhibited generation of hydroxyl radical from albumin-Amadori and protected tryptophan from oxidation by hydroxyl radical species. We conclude that oxidative degradation of either glucose or the protein-Amadori intermediate causes oxidative modification of protein tryptophan residues via hydroxyl radical and can affect protein function under physiologically relevant conditions. This oxidative stress-induced structural and functional protein damage can be ameliorated by PM via sequestration of catalytic metal ions and scavenging of hydroxyl radical, a mechanism that may contribute to the reported therapeutic effects of PM in the complications of diabetes.