A systematic review of viral transmission risk to healthcare staff comparing laparoscopic and open surgery.

BACKGROUND: Throughout the United Kingdom, there have been sweeping changes to the practice of medicine due to the COVID-19 pandemic. For the surgical speciality, there have been changes to both elective and emergency practice. Concern regarding potential aerosolisation during invasive procedures have been raised - including the use of pneumoperitoneum to facilitate laparoscopy. The aim of this study is to systematically review the data available to date regarding the potential risk posed to theatre staff by laparoscopy. METHOD: A systematic review and meta-analysis was carried out in accordance with PRISMA guidelines. Only publications in peer-reviewed journals were considered. PubMed, Ovid Embase, SCOPUS, and Cochrane Library were searched. The search period was between 1st January 1980 and 27th April 2020. Bias was assessed using the ROBINS-I tool. RESULTS: 4209 records were identified, resulting in 9 unique studies being selected. The included studies examined viral DNA aerosoliation generated by electrosurgery and CO2 laser ablation, with one study examining viral DNA aerosolisation following laparoscopy. Each of these demonstrated that viral DNA (Hepatitis B Virus and Human Papilloma Virus) was detectable in the surgical smoke plume. CONCLUSION: The data and analysis reported in this study reflect the most up-to-date evidence available for the surgeon to assess risk towards healthcare staff. It was constrained by heterogeneity of reporting for several outcomes and lack of comparable studies. There is currently insufficient data to recommend open or a minimally invasive surgical approach with regard to theatre team safety in the COVID-19 era.

Meta-analysis of patient-reported outcomes after laparoscopic versus open inguinal hernia repair.

BACKGROUND: Inguinal hernia repair is a common low-risk intervention. Patient-reported outcomes (PROs) are being used increasingly as primary outcomes in clinical trials. The aim of this study was to review and meta-analyse the PROs in RCTs comparing laparoscopic versus open inguinal hernia repair techniques in adult patients. METHODS: A systematic review and meta-analysis was carried out in accordance with PRISMA guidelines. Only RCTs in peer-reviewed journals were considered. PubMed, Ovid Embase, Scopus and the Cochrane Library were searched. In addition, four trial registries were searched. The search interval was between 1 January 1998 and 1 May 2018. Identified publications were reviewed independently by two authors. The review was registered in the PROSPERO database (CRD42018099552). Bias was assessed using the Cochrane Collaboration risk-of-bias tool. RESULTS: Some 7192 records were identified, from which 58 unique RCTs were selected. Laparoscopic hernia repair was associated with significantly less postoperative pain in three intervals: from 2 weeks to within 6 months after surgery (risk ratio (RR) 0·74, 95 per cent c.i. 0·62 to 0·88), 6 months to 1 year (RR 0·74, 0·59 to 0·93) and 1 year onwards (RR 0·62, 0·47 to 0·82). Paraesthesia (RR 0·27, 0·18 to 0·40) and patient-reported satisfaction (RR 0·91, 0·85 to 0·98) were also significantly better in the laparoscopic repair group. CONCLUSION: The data and analysis reported in this study reflect the most up-to-date evidence available for the surgeon to counsel patients. It was constrained by heterogeneity of reporting for several outcomes.

FKRP-dependent glycosylation of fibronectin regulates muscle pathology in muscular dystrophy.

The muscular dystrophies encompass a broad range of pathologies with varied clinical outcomes. In the case of patients carrying defects in fukutin-related protein (FKRP), these diverse pathologies arise from mutations within the same gene. This is surprising as FKRP is a glycosyltransferase, whose only identified function is to transfer ribitol-5-phosphate to α-dystroglycan (α-DG). Although this modification is critical for extracellular matrix attachment, α-DG's glycosylation status relates poorly to disease severity, suggesting the existence of unidentified FKRP targets. Here we reveal that FKRP directs sialylation of fibronectin, a process essential for collagen recruitment to the muscle basement membrane. Thus, our results reveal that FKRP simultaneously regulates the two major muscle-ECM linkages essential for fibre survival, and establishes a new disease axis for the muscular dystrophies.

Birdlike growth and mixed-age flocks in avimimids (Theropoda, Oviraptorosauria).

Avimimids were unusual, birdlike oviraptorosaurs from the Late Cretaceous of Asia. Initially enigmatic, new information has ameliorated the understanding of their anatomy, phylogenetic position, and behaviour. A monodominant bonebed from the Nemegt Formation of Mongolia showed that some avimimids were gregarious, but the site is unusual in the apparent absence of juveniles. Here, a second monodominant avimimid bonebed is described from the Iren Dabasu Formation of northern China. Elements recovered include numerous vertebrae and portions of the forelimbs and hindlimbs, representing a minimum of six individuals. Histological sampling of two tibiotarsi from the bonebed reveals rapid growth early in ontogeny followed by unexpectedly early onset of fusion and limited subsequent growth. This indicates that avimimids grew rapidly to adult size, like most extant birds but contrasting other small theropod dinosaurs. The combination of adults and juveniles in the Iren Dabasu bonebed assemblage provides evidence of mixed-age flocking in avimimids and the onset of fusion in young individuals suggests that some of the individuals in the Nemegt Formation bonebed may have been juveniles. Regardless, these individuals were likely functionally analogous to adults, and this probably facilitated mixed-age flocking by reducing ontogenetic niche shift in avimimids.

Cellular rescue in a zebrafish model of congenital muscular dystrophy type 1A.

Laminins comprise structural components of basement membranes, critical in the regulation of differentiation, survival and migration of a diverse range of cell types, including skeletal muscle. Mutations in one muscle enriched Laminin isoform, Laminin alpha2 (Lama2), results in the most common form of congenital muscular dystrophy, congenital muscular dystrophy type 1A (MDC1A). However, the exact cellular mechanism by which Laminin loss results in the pathological spectrum associated with MDC1A remains elusive. Here we show, via live tracking of individual muscle fibres, that dystrophic myofibres in the zebrafish model of MDC1A maintain sarcolemmal integrity and undergo dynamic remodelling behaviours post detachment, including focal sarcolemmal reattachment, cell extension and hyper-fusion with surrounding myoblasts. These observations imply the existence of a window of therapeutic opportunity, where detached cells may be "re-functionalised" prior to their delayed entry into the cell death program, a process we show can be achieved by muscle specific or systemic Laminin delivery. We further reveal that Laminin also acts as a pro-regenerative factor that stimulates muscle stem cell-mediated repair in lama2-deficient animals in vivo. The potential multi-mode of action of Laminin replacement therapy suggests it may provide a potent therapeutic axis for the treatment for MDC1A.

A dinosaur community composition dataset for the Late Cretaceous Nemegt Basin of Mongolia.

Dinosaur community composition data for eleven fossil localities in the Late Cretaceous Nemegt Basin of Mongolia are compiled from field observations and records in the literature. Counts were generated from skeletons and represent numbers of individuals preserved in each locality. These data were used in the analyses of Funston et al. [1] "Oviraptorosaur anatomy, diversity, and ecology in the Nemegt Basin" in the Nemegt Ecosystems Special Issue of Palaeogeography, Palaeoclimatology, Palaeoecology, where the results are discussed.

Zebrafish genetics: mutant cornucopia.

The initial characterization of mutations from the large-scale mutagenesis of the zebrafish genome has been reported. What new insights will we gain about vertebrate development from these studies?

Muscular dystrophy modeling in zebrafish.

Skeletal muscle performs an essential function in human physiology with defects in genes encoding a variety of cellular components resulting in various types of inherited muscle disorders. Muscular dystrophies (MDs) are a severe and heterogeneous type of human muscle disease, manifested by progressive muscle wasting and degeneration. The disease pathogenesis and therapeutic options for MDs have been investigated for decades using rodent models, and considerable knowledge has been accumulated on the cause and pathogenetic mechanisms of this group of human disorders. However, due to some differences between disease severity and progression, what is learned in mammalian models does not always transfer to humans, prompting the desire for additional and alternative models. More recently, zebrafish have emerged as a novel and robust animal model for the study of human muscle disease. Zebrafish MD models possess a number of distinct advantages for modeling human muscle disorders, including the availability and ease of generating mutations in homologous disease-causing genes, the ability to image living muscle tissue in an intact animal, and the suitability of zebrafish larvae for large-scale chemical screens. In this chapter, we review the current understanding of molecular and cellular mechanisms involved in MDs, the process of myogenesis in zebrafish, and the structural and functional characteristics of zebrafish larval muscles. We further discuss the insights gained from the key zebrafish MD models that have been so far generated, and we summarize the attempts that have been made to screen for small molecules inhibitors of the dystrophic phenotypes using these models. Overall, these studies demonstrate that zebrafish is a useful in vivo system for modeling aspects of human skeletal muscle disorders. Studies using these models have contributed both to the understanding of the pathogenesis of muscle wasting disorders and demonstrated their utility as highly relevant models to implement therapeutic screening regimens.

A systematic review and meta-analysis of the post-operative adverse effects associated with mosquito net mesh in comparison to commercial hernia mesh for inguinal hernia repair in low income countries.

PURPOSE: Abdominal wall hernia is a common surgical condition, with more than 20 million estimated to be repaired each year. Mesh repair is the standard for most repairs; however, the mesh material itself may be a barrier to care, the cost prohibitively high for some populations and healthcare systems. The aim of this systematic review and meta-analysis was to produce a pooled comparison between the adverse event rate associated with mosquito net mesh and commercial hernia mesh. METHODS: A systematic review was carried out in accordance with PRISMA guidelines. PubMed, Ovid Embase/Medline, SCOPUS, Web of Science and the Cochrane library were searched. In addition, the ISRCTN register, ClinicalTrials.gov, ICTR Platform and EU Clinical Trials Register were searched. RESULTS: Five randomised controlled trials (RCTs) were identified. The RCTs were deemed to have similar sample populations after inspection of their sample parameters. Therefore, the adverse effects were compared individually (reoccurrence, haematoma, seroma, infection, and serous discharge) and pooled. A total of 313 mosquito net meshes were included in the study, there was no significant difference between the intervention and control groups for pooled adverse effects or individually. CONCLUSIONS: There is not a significant difference between the commercial mesh group and the mosquito net mesh group for pooled [odds ratio 0.93 (0.63, 1.35)] and individual adverse event rates. However, the 95% confidence intervals of these results are still wide. To reduce this uncertainty sample sizes must increase in future studies.

Involvement of opioid signaling in food preference and motivation: Studies in laboratory animals.

Motivation is a complex neurobiological process that initiates, directs, and maintains goal-oriented behavior. Although distinct components of motivated behavior are difficult to investigate, appetitive and consummatory phases of motivation are experimentally separable. Different neurotransmitter systems, particularly the mesolimbic dopaminergic system, have been associated with food motivation. Over the last two decades, however, research focusing on the role of opioid signaling has been particularly growing in this area. Opioid receptors seem to be involved, via neuroanatomically distinct mechanisms, in both appetitive and consummatory aspects of food reward. In the present chapter, we review the pharmacology and functional neuroanatomy of opioid receptors and their endogenous ligands, in the context of food reinforcement. We examine literature aimed at the development of laboratory animal techniques to better understand different components of motivated behavior. We present recent data investigating the effect of opioid receptor antagonists on food preference and effort-related decision making in rats, which indicate that opioid signaling blockade selectively affects intake of relatively preferred foods, resulting in reduced willingness to exert effort to obtain them. Finally, we elaborate on the potential role of opioid system manipulations in disorders associated with excessive eating and obesity.

Diabetes mellitus in an urbanized, isolated Polynesian population. The Funafuti survey.

An epidemiologic study of diabetes in the urbanized Polynesian population of Funafuti has established a prevalence of 8 per cent in subjects aged 10 years and over. Of these, 0.9 per cent were known diabetics, and the remainder were diagnosed on the basis of a plasma glucose level of at least 160 mg./100 ml. two hours after a 75 gm. glucose load. A further 5.9 per cent had borderline diabetes as judged by a two-hour postload plasma glucose of 140-159 mg./100 ml. In those aged 20 years and over, the prevalence of diabetes was 10.1 per cent, similar to that reported in other acculturated Polynesian groups. The prevalence of both borderline diabetes and frank diabetes was twice as high in the females as in males. This difference appeared to be related to the greater degree of obesity in the females, but the prevalence was not related to parity. The increase in frequency of diabetes among these islanders coincides with a change of traditional island life style to that of urbanized Western populations. The results suggest that there may be 10 times the actual number of known diabetics in some Pacific populations.

Comparison of three Doppler ultrasound methods in the prediction of pulmonary artery pressure.

Pulmonary artery pressure was noninvasively estimated by three Doppler echocardiographic methods in 50 consecutive patients undergoing cardiac catheterization. First, a systolic transtricuspid gradient was calculated from Doppler-detected tricuspid regurgitation; clinical jugular venous pressure or a fixed value of 14 mm Hg was added to yield systolic pulmonary artery pressure. Second, acceleration time from pulmonary flow analysis was used in a regression equation to derive mean pulmonary artery pressure. Third, right ventricular isovolumic relaxation time was calculated from Doppler-determined pulmonary valve closure and tricuspid valve opening; systolic pulmonary artery pressure was then derived from a nomogram. In 48 patients (96%) at least one of the methods could be employed. A tricuspid pressure gradient, obtained in 36 patients (72%), provided reliable prediction of systolic pulmonary artery pressure. The prediction was superior when 14 mm Hg rather than estimated jugular venous pressure was used to account for right atrial pressure. In 44 patients (88%), pulmonary flow was analyzed. Prediction of mean pulmonary artery pressure was unsatisfactory (r = 0.65) but improved (r = 0.85) when only patients with a heart rate between 60 and 100 beats/min were considered. The effect of correcting pulmonary flow indexes for heart rate was examined by correlating different flow indexes before and after correction for heart rate. There was a good correlation between corrected acceleration time and either systolic (r = -0.85) or mean (r = -0.83) pulmonary artery pressure. Because of a high incidence of arrhythmia, right ventricular relaxation time could be determined in only 11 patients (22%). Noninvasive prediction of pulmonary artery pressure is feasible in most patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Instantaneous pressure gradient: a simultaneous Doppler and dual catheter correlative study.

To more precisely measure the beat to beat and instantaneous pressure gradients across outflow stenotic lesions, simultaneous Doppler and dual catheter pressure gradient measurements were performed in 95 patients (mean age 42 years, range 1.5 to 85). There were 38 right ventricular and 62 left ventricular outflow obstructive lesions. Forty-nine patients also had a nonsimultaneous Doppler study performed within 7 days before catheterization. The simultaneous pressure waveforms and Doppler spectral velocity profiles were digitized at 10 ms intervals deriving maximal, mean and instantaneous gradients (mm Hg). For simultaneous maximal Doppler and catheter gradient measurements, the correlation coefficient (r) was 0.95 (SEE = 10 mm Hg), for Doppler and catheter mean gradients it was 0.94 (SEE = 8 mm Hg) and for maximal Doppler and peak to peak catheter gradients it was 0.92 (SEE = 13 mm Hg). The correlation of maximal and mean Doppler gradients with the respective catheter gradients was similarly high when the right and left ventricular outflow lesions were analyzed separately. However, the maximal Doppler gradient was significantly higher than the peak to peak catheter gradient. This was more evident with left ventricular outflow stenotic lesions. The correlation of the outpatient maximal Doppler and catheter gradients (r = 0.80, SEE = 17 mm Hg) was significantly lower than the simultaneous correlation (r = 0.96, SEE = 10 mm Hg) in the 49 patients with two Doppler studies. Continuous wave Doppler echocardiography accurately measures the instantaneous pressure gradient across both left and right ventricular outflow obstructive lesions. The maximal Doppler gradient should not be equated with the peak to peak catheter gradient.(ABSTRACT TRUNCATED AT 250 WORDS)

Evaluation of mitral leaflet motion by echocardiography and jet direction by Doppler color flow mapping to determine the mechanisms of mitral regurgitation.

OBJECTIVES: This study was designed to assess the accuracy of two-dimensional and Doppler echocardiography in determining the mechanism of mitral regurgitation, as compared with direct inspection of the valve at operation. BACKGROUND: Valve repair for mitral regurgitation offers substantial advantages over valve replacement, but it is technically more demanding and requires understanding of the mechanism of dysfunction. METHODS: We studied 286 patients undergoing mitral valve repair. Intraoperative two-dimensional echocardiography was used to classify mitral leaflet motion as excessive, normal or restricted. Doppler color flow mapping was used to evaluate the direction and origin of the mitral regurgitant jet. Two-dimensional and Doppler echocardiography were compared with intraoperative surgical determination of the mechanism of dysfunction, which also classified leaflet motion as excessive, normal or restricted. RESULTS: Two-dimensional and Doppler echocardiography accurately diagnosed the mechanism of mitral regurgitation in 123 (93%) of 132 patients with posterior leaflet prolapse or flail, 30 (94%) of 32 patients with anterior leaflet prolapse or flail, 11 (44%) of 25 patients with bileaflet prolapse or flail, 6 (75%) of 8 patients with papillary muscle elongation or rupture, 31 (91%) of 34 patients with restricted leaflet motion or rheumatic thickening, 21 (72%) of 29 patients with ventricular-annular dilation and 8 (62%) of 13 patients with a leaflet perforation or cleft. Of 13 patients with two mechanisms of dysfunction by surgical inspection, two-dimensional and Doppler echocardiography correctly diagnosed one of the two mechanisms in 12 patients (92%), and both mechanisms in 5 patients (38%). Overall, echocardiographic determination of leaflet motion and Doppler determination of jet direction accurately diagnosed the mechanism of dysfunction in 242 (85%) of 286 patients. CONCLUSIONS: Echocardiography before mitral valvuloplasty provides a dynamic appraisal of the mechanism of dysfunction, enabling the surgeon to systematically understand the dysfunction and successfully apply the correct procedures to eliminate mitral regurgitation without valve replacement.

Oral beta-adrenergic blockade with metoprolol in chronic severe dilated cardiomyopathy.

A double-blind crossover trial was performed to assess the effect of metoprolol in 10 patients (mean age 55 years) with severe dilated cardiomyopathy. All patients clinically had idiopathic dilated cardiomyopathy; however, at coronary angiography, four had occult coronary disease. All were in New York Heart Association functional class III with a left ventricular ejection fraction less than 35% as assessed by rest radionuclide ventriculography. Studies were performed before treatment, after 4 weeks of metoprolol therapy and after 4 weeks of placebo administration. Erect bicycle sprint exercise was used to determine maximal work load. Hemodynamic variables and radionuclide left ventricular ejection fraction were recorded at rest and during graded supine bicycle exercise. Cardiac medications were unchanged throughout the trial. The mean (+/- standard error of the mean) dose of metoprolol was 130 +/- 13 mg/day. Metoprolol did not change symptoms, chest X-ray findings or exercise tolerance (baseline 700 +/- 73, placebo 690 +/- 85, metoprolol 710 +/- 81 kilopond-meters [kpm]/min). Metoprolol produced a significant decrease in heart rate at rest and during exercise (p less than 0.001). Mean blood pressure and left ventricular filling pressure did not differ significantly in the baseline, placebo and metoprolol studies. There was a slight, but significant (p less than 0.05) decrease in cardiac index with metoprolol compared with placebo and baseline studies. The small, but significant increase in left ventricular ejection fraction from baseline to the metoprolol and placebo studies (p less than 0.001) was considered a result of spontaneous improvement rather than of therapy. No significant differences were found between the patients with and without coronary disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Extracardiac conduit obstruction: initial experience in the use of Doppler echocardiography for noninvasive estimation of pressure gradient.

Extracardiac valved conduits are often employed in the repair of certain complex congenital heart defects; late obstruction is a well recognized problem that usually requires catheterization for definitive diagnosis. A reliable noninvasive method for detecting conduit stenosis would be clinically useful in identifying the small proportion of patients who develop this problem. Continuous wave Doppler echocardiography has been used successfully to estimate cardiac valvular obstructive lesions noninvasively. Twenty-three patients with prior extracardiac conduit placement for complex congenital heart disease underwent echocardiographic and continuous wave Doppler echocardiographic examinations to determine the presence and severity of conduit stenosis. In 20 of the 23 patients, an adequate conduit flow velocity profile was obtained, and in 10 an abnormally increased conduit flow velocity was present. All but one patient had significant obstruction proven at surgery and in one patient, surgery was planned. In three patients, an adequate conduit flow velocity profile could not be obtained but obstruction was still suspected based on high velocity tricuspid regurgitant Doppler signals. In these three patients, subsequent surgery also proved that conduit stenosis was present. Doppler-predicted gradients and right ventricular pressures showed an overall good correlation (r = 0.90) with measurements at subsequent cardiac catheterization. Continuous wave Doppler echocardiography appears to be a useful noninvasive tool for the detection and semiquantitation of extracardiac conduit stenosis.

Continuous wave Doppler determination of right ventricular pressure: a simultaneous Doppler-catheterization study in 127 patients.

Simultaneous continuous wave Doppler echocardiography and right-sided cardiac pressure measurements were performed during cardiac catheterization in 127 patients. Tricuspid regurgitation was detected by the Doppler method in 117 patients and was of adequate quality to analyze in 111 patients. Maximal systolic pressure gradient between the right ventricle and right atrium was 11 to 136 mm Hg (mean 53 +/- 29) and simultaneously measured Doppler gradient was 9 to 127 mm Hg (mean 49 +/- 26); for these two measurements, r = 0.96 and SEE = 7 mm Hg. Right ventricular systolic pressure was estimated by three methods from the Doppler gradient. These were 1) Doppler gradient + mean jugular venous pressure; 2) using a regression equation derived from the first 63 patients (Group 1); and 3) Doppler gradient + 10. These methods were tested on the remaining 48 patients with Doppler-analyzable tricuspid regurgitation (Group 2). The correlation between Doppler-estimated and catheter-measured right ventricular systolic pressure was similar using all three methods; however, the regression equation produced a significantly better estimate (p less than 0.05). Use of continuous wave Doppler blood flow velocity of tricuspid regurgitation permitted determination of the systolic pressure gradient across the tricuspid valve and the right ventricular systolic pressure. This noninvasive technique yielded information comparable with that obtained at catheterization. Approximately 80% of patients with increased and 57% with normal right ventricular pressure had analyzable Doppler tricuspid regurgitant velocities that could be used to accurately predict right ventricular systolic pressure.

Structure, expression and duplication of genes which encode phosphoglyceromutase of Drosophila melanogaster.

We report here the isolation and characterization of genes from Drosophila that encode the glycolytic enzyme phosphoglyceromutase (PGLYM). Two genomic regions have been isolated that have potential to encode PGLYM. Their cytogenetic localizations have been determined by in situ hybridization to salivary gland chromosomes. One gene, Pglym78, is found at 78A/B and the other, Pglym87, at 87B4,5 of the Drosophila polytene map. Pglym78 transcription follows a developmental pattern similar to other glycolytic genes in Drosophila, i.e., substantial maternal transcript deposited during oogenesis; a decline in abundance in the first half of embryogenesis; a subsequent increase in the second half of embryogenesis which continues throughout larval life; a decline in pupae and a second increase to a plateau in adults. This transcript has been mapped by cDNA and genomic sequence comparison, RNase protection, and primer extension. Using similar analyses transcripts of Pglym87 could not be detected. Pglym78 has two introns which interrupt the coding region, while the Pglym87 gene lacks introns. This and other features support a model of retrotransposition mediated gene duplication for the origin of Pglym87. The apparent absence of a complete, intact coding frame and transcript suggest that Pglym87 is a pseudogene. However, retention of reading frame and codon bias suggests that Pglym87 may retain coding function, or may have been inactivated recently, substantially after the time of duplication, or that the molecular evolution of Pglym87 is unusual. Similarities of the unusual molecular evolution of Pglym87 and other proposed pseudogenes are discussed.

Intragenic dominant suppressors of glp-1, a gene essential for cell-signaling in Caenorhabditis elegans, support a role for cdc10/SWI6/ankyrin motifs in GLP-1 function.

The glp-1 gene product mediates cell-cell interactions required for cell fate specification during development in Caenorhabditis elegans. To identify genes that interact with glp-1, we screened for dominant suppressors of two temperature-sensitive glp-1 alleles and recovered 18 mutations that suppress both germline and embryonic glp-1 phenotypes. These dominant suppressors are tightly linked to glp-1 and do not bypass the requirement for a distal tip cell, which is thought to be the source of a signal that is received and transduced by the GLP-1 protein. Using single-strand conformation polymorphism (SSCP) analysis and DNA sequencing, we found that at least 17 suppressors are second-site intragenic revertants. The suppressors, like the original glp-1(ts) mutations, are all located in the cdc10/SWI6/ankyrin domain of GLP-1. cdc10/SWI6/ankyrin motifs have been shown to mediate specific protein-protein interactions in other polypeptides. We propose that the glp-1(ts) mutations disrupt contact between GLP-1 and an as yet unidentified target protein(s) and that the dominant suppressor mutations restore appropriate protein-protein interactions.

The generation and interpretation of positional information within the vertebrate myotome.

How somitic cells become restricted to the muscle fate has been investigated on a number of levels. Classical embryological manipulations have attempted to define the source of inductive signals that control the formation of the myotome. Recently, these studies have converged with others dissecting the role of secreted proteins in embryonic patterning to demonstrate a role for specific peptides in inducing individual cell types of the myotome. Collectively, these investigations have implicated the products of the Wnt, Hedgehog (Hh) and Bone morphogenetic protein (Bmp) gene families as key myogenic regulators; simultaneously controlling both the initiation of myogenesis and the fate of individual myoblasts.