Macrophage-specific expression of human lysosomal acid lipase corrects inflammation and pathogenic phenotypes in lal(-/-) mice

Lysosomal acid lipase (LAL) hydrolyzes cholesteryl esters and triglycerides to generate free fatty acids and cholesterol in the cell. The downstream metabolites of these compounds serve as hormonal ligands for nuclear receptors and transcription factors. Genetic ablation of the lal gene in the mouse caused malformation of macrophages and inflammation-triggered multiple pathogenic phenotypes in multiple organs. To assess the relationship between macro phages and lal(-/-) pathogenic phenotypes, a macrophage-specific doxycycline-inducible transgenic system was generated to induce human LAL (hLAL) expression in the lal(-/-) genetic background under control of the 7.2-kb c-fins promoter/intron2 regulatory sequence. Doxycycline-induced hLAL expression in macrophages significantly ameliorated aberrant gene expression, inflammatory cell (neutrophil) influx, and pathogenesis in multiple organs. These studies strongly support that neutral lipid metabolism in macrophages contributes to organ inflammation and pathogenesis.

The human genome and gene expression profiling

The mapping and sequencing of the human genome has generated a large resource for answering questions about human disease. This achievement is akin in scientific importance to developing the periodic table of elements. Plastic surgery has always been at the frontier medical research. This resource will help us to improve our understanding on the many unknown physiological and pathogical conditions we deal with daily, such as wound heating keloid scar formation, Dupuytren's disease, rheumatoid arthritis, vascular malformation and carcinogenesis. We are primed in obtaining both disease and normal tissues to use this resource and applying it to clinical use. This review is about the human genome, the basis of gene expression profiling and how it will affect our clinical and research practices in the future and for those embarking on the use of this new technology as a research tool, we provide a brief insight on its limitations and pitfalls. (C) 2006 The British Association of Plastic Surgeons. Published by Elsevier Ltd. All rights reserved.

Further evaluation of an EMG technique for assessment of the deep cervical flexor muscles

A novel surface electromyographic (EMG) technique was recently described for the detection of deep cervical flexor muscle activity. Further investigation of this technique is warranted to ensure EMG activity from neighbouring muscles is not markedly influencing the signals recorded. This study compared deep cervical flexor (DCF) muscle activity with the activity of surrounding neck and jaw muscles during various anatomical movements of the neck and jaw in 10 volunteer subjects. DCF EMG activity was recorded with custom electrodes inserted via the nose and fixed by suction to the posterior mucosa of the oropharynx. Surface electrodes were placed over the sternocleidomastoid, anterior scalene, masseter and suprahyoid muscles. Positioned in supine, subjects performed isometric cranio-cervical flexion, cervical flexion, right and left cervical rotation,jaw clench and resisted jaw opening. Across all movements examined, EMG amplitude of the DCF muscles was greatest during neck movements that would require activity of the DCF muscles, particularly during cranio-cervical flexion, their primary anatomical action. The actions of jaw clench and resisted jaw opening demonstrated significantly less DCF EMG activity than the cranio-cervical flexion action (p < 0.05). Across all other movements, the neighbouring neck and jaw muscles demonstrated greatest EMG amplitude during their respective primary anatomical actions, which occurred in the absence of increased EMG amplitude recorded from the DCF muscles. The finding of substantial EMG activity of the DCF muscles only during neck actions that would require their activity, particularly cranio-cervical flexion, and not during actions involving the jaw, provide further assurance that the majority of myoelectric signals detected from the nasopharyngeal electrode are from the DCF muscles. (C) 2005 Elsevier Ltd. All rights reserved.

Increased DNA Methylation at the AXIN1 Gene in a Monozygotic Twin from a Pair Discordant for a Caudal Duplication Anomaly

The AXIN1 gene has been implicated in caudal duplication anomalies. Its coding region was sequenced in both members of a monozygotic ( MZ) twin pair discordant for a caudal duplication anomaly, but no mutation was found. Using bisulfite sequencing, we examined methylation at the promoter region of the AXIN1 gene in these twins and in twin and age-matched singleton controls. Methylation of the promoter region in peripheral blood mononucleated cells was variable among individuals, including MZ pairs. In the MZ pair discordant for the caudal duplication, this region of the affected twin was significantly more methylated than that of the unaffected twin (), which was significantly more P < .0001 methylated than those of the controls (). We have confirmed that this CpG island does function as a promoter P = .02 in vitro and that its activity is inversely proportional to the extent of methylation. This finding raises the possibility that hypermethylation of the AXIN1 promoter, by mechanisms as yet undetermined, is associated with the malformation. This case may be paradigmatic for some cases of MZ discordance.

Inferring parrotfish (Teleostei : Scaridae) pharyngeal mill function from dental morphology, wear, and microstructure

Morphology, occlusal surface topography, macrowear, and microwear features of parrotfish pharyngeal teeth were investigated to relate microstructural characteristics to the function of the pharyngeal mill using scanning electron microscopy of whole and sectioned pharyngeal jaws and teeth. Pharyngeal tooth migration is anterior in the lower jaw (fifth ceratobranchial) and posterior in the upper jaw (paired third pharyngobranchials), making the interaction of occlusal surfaces and wear-generating forces complex. The extent of wear can be used to define three regions through which teeth migrate: a region containing newly erupted teeth showing little or no wear; a midregion in which the apical enameloid is swiftly worn; and a region containing teeth with only basal enameloid remaining, which shows low to moderate wear. The shape of the occlusal surface alters as the teeth progress along the pharyngeal jaw, generating conditions that appear suited to the reduction of coral particles. It is likely that the interaction between these particles and algal cells during the process of the rendering of the former is responsible for the rupture of the latter, with the consequent liberation of cell contents from which parrotfish obtain their nutrients.

Microvertebrate assemblages from the Upper Silurian of Cornwallis Island, Arctic Canada

Microvertebrate assemblages from four Upper Silurian (?Ludlow-Pridoli) localities on Cornwallis Island, Arctic Canada, comprise mainly scales, plus dentition cones and jaw fragments from ischnacanthid acanthodians, with rare scales assigned to heterostracan Lepidaspis? sp., ?chondrichthyan Arauzia? sp., and Placodermi? gen. et sp. indet. Most of the scales in sample C-11460 are assigned to the poracanthodid acanthodian Poracanthodes canadensis sp.nov., which shows closest affinity to Poracanthodes punctatus Brotzen variants from the Baltic Pridoli. The flank scales of the new species resemble those of P. punctatus s.s. (Silurian variant; the zone fossil for the late Pridoli in the Standard Silurian microvertebrate scheme), with their superposed crown growth zones, rows of small pores aligned with the underlying zones, number of radial canals, and arcade canals connecting these radial canals. They differ in having numerous anterior crown riblets, zig-zag rather than straight crown pore rows, and V-shaped arcade canals.