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Genetic control of retinal specification and determination in Drosophila.

The Drosophila compound eye has long served as an outstanding model system to study many processes, including cell fate specification, cell division, cell growth and cell death. In addition, exploring the molecular basis of eye specification in Drosophila has identified a set of nuclear factors that trigger the conversion of a group of multipotent epithelial cells into eye primordia. These nuclear factors act in complex networks to regulate retinal specification and appear to be conserved throughout phylogeny. Finally, evidence suggests that these nuclear networks have been co-opted to specify cell fates in other tissues. We review the latest developments in the field of retinal specification in Drosophila and discuss several future directions that remain open for investigation.

Animals↗

Historical perspective on the development and evolution of eyes and photoreceptors.

The development and evolution of eyes is an "old problem" in biology, which required a special treatment in Charles Darwin's "Origin of the species" (1882) under the heading of "Difficulties of the theory". Darwin postulated a simple and imperfect eye, as a prototype, which can vary and evolve under natural selection into more complex and perfect eyes. Based upon morphological criteria and the different modes of development of the different kinds of eyes, neodarwinists have postulated that the various eye-types are polyphyletic in origin and that the eyes have evolved independently in the various animal phyla. Recent developmental genetic experiments and molecular phylogenetic analyses cast serious doubts on this interpretation and argue strongly for a monophyletic origin of the eyes from a Darwinian prototype and subsequent divergent, parallel and convergent evolution leading to the various eye-types.

Animals↗

The germ line lineage in ukigori, Gymnogobius species (Teleostei: Gobiidae) during embryonic development.

In order to determine the origin and migration of ukigori primordial germ cells (PGCs), we observed the aggregation of vasa mRNA by whole mount in situ hybridization. To observe PGC migration in the germ layers, we analyzed HE-stained paraffin sections. The germ line lineages were derived from the edge of the first, second and third cleavage furrows. During subsequent cleavages, vasa mRNA aggregations were respectively taken into four to eight cells in each embryo and vasa expressing cells proliferated from the sphere stage. At the bud to early somitogenesis period, PGCs aligned from head to tail bud regions on both sides of the embryonic body. During the late somitogenesis period, PGCs mainly aggregated just underneath the body axis. After gut formation, PGCs aligned along both sides of the gut at the 4th- to 8th- somite regions. Finally, PGCs reached the genital ridge via the inside of the lateral plate mesoderm and dorsal peritoneum. These results suggest that localized patterns of vasa transcripts and the migration routes of PGCs are different among fish (Teleost) species, perhaps depending on the amount of germinal cytoplasm derived maternally and the timing of endoderm differentiation.

Animals↗

Head-tail patterning of the vertebrate embryo: one, two or many unresolved problems?

When, where and how is the head-tail axis of the embryo set up during development? These are such fundamental and intensely studied questions that one might expect them to have been answered long ago. Not so; we still understand very little about the cellular or molecular mechanisms that lead to the orderly arrangement of body elements along the head-tail axis in vertebrates. In this paper, we outline some of the major outstanding problems and controversies and try to identify some reasons why it has been so difficult to resolve this important issue.

Animals↗

Stresses created by occlusal prematurities in a new photoelastic model system.

A new photoelastic model system incorporating a simulated periodontal ligament sleeve around an experimental first molar has been developed. The system was used to visualize internal compressive stresses created by various premature occlusal incline relationships in both buccolingual and mesiodistal dimensions. When prematurities were applied singly and observed buccolingually, both class 1 and and class 2 prematurities produced stresses along the lingual aspect of the root, whereas the class 3 prematurity produced stresses along the buccal aspect of the root. When viewed buccolingually, combinations of class 1 and class 2 prematurities resulted in stresses along the lingual aspect of the root. The stress pattern was similar to those created by the single class 1 or class 2 prematurities. A combination of class 2 and class 3 prematurities did not produce a well-defined indication of stress distribution. There was slightly more stress along the buccal aspect of the root. Comparison of this combination with individual class 2 and class 3 prematurities indicates that such a combination tended to diminish tipping of the tooth in any one direction. A combination of class 1 and class 3 prematurities showed slightly greater stress along the buccal aspect of the root surface. Again, the combination produced less tipping of the tooth in any one direction when compared with tipping caused by the individual prematurities. When all three prematurities were tested at the same time, the stress pattern was almost coincident with that achieved in the absence of prematurities. When prematurities were observed mesiodistally, the location of stresses was dependent on the mesial or distal placement of the prematurity, irrespective of its position buccolingually.

Dental Occlusion, Traumatic↗

Pressure volume curve and alveolar recruitment/de-recruitment. A morphometric model of the respiratory cycle.

HYPOTHESIS: The changes in pulmonary volume taking place during respiration are accompanied by the opening and closing of the alveoli, with the number of alveoli open, at the same transpulmonary pressure (TPP) differing, depending on whether the lung is insufflated or deflated. MATERIAL AND METHODS: Seventy 344 Fischer rats divided into five groups. Group 1 lungs were fixed by instilling 10% formalin through the trachea to a pressure of 25 cm H2O. The lungs of the next four groups were air-filled and fixed via the pulmonary artery: group 2 lungs were fixed in inflation at 10 cm H2O TPP; group 3 lungs were fixed in inflation at 20 cm. H2O TPP; the lungs of groups 4 and 5 were fixed in deflation and, therefore, were inflated with air up to 27 cm. H2O to drop to 20 cm in group 4 and to 10 cm in group 5. The lungs were processed for light microscopy, carrying out a morphometric study. The results were statistically processed. RESULTS: The lungs insufflated with liquid fixative at 25 cm of TPP reached higher values in the variables Pulmonary Volume, Internal Alveolar Surface (IAS) and Number of Alveoli, being statistically significant (p < 0.05) in comparison with the other four groups. In the lungs fixed in deflation, the pulmonary volume, IAS and number of alveoli were greater than in those fixed in inflation. The lungs fixed to 20 cm in deflation displayed significant statistical differences compared with those fixed to 20 cm in inflation. The IAS and number of alveoli gave good rates in relation with the pulmonary volume (r > or = 0.65). Three variables were used to measure the size of the alveoli, alveolar cord, alveolar surface and Lm, but none showed significant modifications. CONCLUSION: This study supports the hypothesis that changes in lung volume are related to the increase/decrease in the number of alveoli that are open/closed and not to the modification in the size of the alveoli. Alveolar recruitment is the microscopic expression of pulmonary hysteresis, since the number of alveoli open in deflation is greater than the number open during inflation.

Animals↗

Bone marrow angiogenesis: methods of quantification and changes evolving in chronic myeloproliferative disorders.

Until now little information is available about bone marrow (BM) angiogenesis in chronic myeloproliferative disorders (CMPDs). Amongst the various immunohistochemical markers for endothelial cells CD34 and CD105 have proven to be most reliable since they exhibit no relevant co-staining. Determination of vascularity has to include pathophysiological aspects of perfusion. Therefore, quantification of the microvascular density (MVD) by the so-called hot spot method has to be improved by parameters that characterize blood flow more properly like microvessel area (luminal distension), shape (form factor), tortuosity, and branching (maximal vessel length). In comparison to the normal BM chronic myeloid leukemia (CML) revealed a significant increase in MVD which was functionally associated with elevated levels of angiogenic cytokines. Structure of vessels was significantly altered by showing an enhanced irregularity of shape and tortuosity and increase in fibers was conspicuously accompanied by a higher degree of MVD. Contrasting the group of patients with Imatinib (STI571) therapy interferon failed to reduce the number of vessels. Following bone marrow transplantation a significant enhancement of the MVD was found in the early post-transplant period, but after about 6 months normalization occurred. Anomalies of microvascular architecture were easily demonstrable by three-dimensional reconstruction and consisted of a complex branching network of irregular shaped sinuses. Chronic idiopathic myelofibrosis displayed a significant increase in the MVD only in the advanced fibrosclerotic stages. This feature was accompanied by an enhanced luminal distension and tortuosity, thus contrasting the prefibrotic and early fibrotic phases of this disorder. Similar to CML a relationship between evolving myelofibrosis and change in vascular architecture was encountered. This feature may present a possible target for future anti-angiogenic therapy. In essential thrombocythemia there is only a mild increase in MVD detectable while in polycythemia vera besides an enlarged number, a luminal dilation due to the densely packed erythrocytes is recognizable. In conclusion, contrasting the usually applied quantification technique more elaborate morphometrical methods are warranted to obtain a better insight into the vascular architecture of the BM. In CMPDs angiogenesis is significantly associated with the evolution of myelofibrosis and may be altered by therapeutic regimens probably due to changes in cytokine release.

Bone Marrow↗

[A planar nonlinear model of the human spine].

In this study the derivation of a two-dimensional mathematical model of the human lumbar spine and its approximate solution using the method of finite elements is described. The computer model LUSP (Lumbar Spine) serves as a basis for studying the kinematic and load-bearing behaviour of the lumbar spine. The underlying working hypothesis is that the smallest spinal unit, the so called functional spinal unit (Junghanns, reflects the basic characteristic behaviour of the musclefree spine. On the basis of Lagrange's virtual work principle the nonlinear static and dynamic equations of motion for a sagitally symmetrical spine model of comprising rigid bodies, springs, beams and dampers are derived. The finite element method is used as an appropriate approximation scheme. Intensive research was conducted to provide the necessary geometrical and material input data. Special attention was paid to achieving a realistic description of the nonlinear stress-strain relationships for the soft tissue involved. A database-type preprocessor and a graphics-oriented postprocessor are made for convenient handling of the input and output data. The efficiency of the present computer model is demonstrated by means of an orthopaedic-biomechanical study on degenerative phenomena in so-called juxta-fused lumbosacral motion segments.

Biomechanical Phenomena↗

Numerical calculations of switched magnetic field gradients during magnetic resonance imaging.

During magnetic resonance imaging (MRI) pulse-sequences the human body is exposed to switched magnetic gradient fields. These gradients become stronger and are switched faster for fast imaging. Effects resulting from these fields with trapezoidal waveforms are on the one hand sensory perception of induced currents and on the other hand muscular and cardiac stimulation. All three components of the current density induced by gradient pulse sequence were analysed in a high-resolution model of the human torso. The evaluation of the calculated data was performed thoroughly in the region of the heart muscle of the torso model to find out how different waveforms of the switched gradient field influence strength and direction of induced currents.

Electrocardiography↗

Sensitivity to auditory object features in human temporal neocortex.

This positron emission tomography study examined the hemodynamic response of the human brain to auditory object feature processing. A continuum of object feature variation was created by combining different numbers of stimuli drawn from a diverse sample of 45 environmental sounds. In each 60 sec scan condition, subjects heard either a distinct individual sound on each trial or simultaneous combinations of sounds that varied systematically in their similarity or distinctiveness across conditions. As more stimuli are combined they become more similar and less distinct from one another; the limiting case is when all 45 are added together to form a noise that is repeated on each trial. Analysis of covariation of cerebral blood flow elicited by this parametric manipulation revealed a response in the upper bank of the right anterior superior temporal sulcus (STS): when sounds were identical across trials (i.e., a noise made up of 45 sounds), activity was at a minimum; when stimuli were different from one another, activity was maximal. A right inferior frontal area was also revealed. The results are interpreted as reflecting sensitivity of this region of temporal neocortex to auditory object features, as predicted by neurophysiological and anatomical models implicating an anteroventral functional stream in object processing. The findings also fit with evidence that voice processing may involve regions within the anterior STS. The data are discussed in light of these models and are related to the concept that this functional stream is sensitive to invariant sound features that characterize individual auditory objects.

Acoustic Stimulation↗