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Molecular transfer of a species-specific behavior from Drosophila simulans to Drosophila melanogaster.

Drosophila males modulate the interpulse intervals produced during their courtship songs. These song cycles, which are altered by mutations in the clock gene period, exhibit a species-specific variation that facilitates mating. We have used chimeric period gene constructs from Drosophila melanogaster and Drosophila simulans in germline transformation experiments to map the genetic control of their song rhythm difference to a small segment of the amino acid encoding information within this gene.

Amino Acid Sequence↗

Seasonal influences on circadian rhythms in the blood picture of SPF rats housed under artificial illumination.

Total leukocyte, erythrocyte, absolute lymphocyte, eosinophil and segmented neutrophil counts in the peripheral blood of SPF rats kept under light/dark 12 h/12 h cycles were investigated with respect to a time standardization of blood drawing for haematological examinations in long-term studies, especially in preclinical safety evaluations of new drugs. Mesor and amplitude were subject to seasonal variations in the circadian rhythm of leukocyte, absolute lymphocyte, segmented neutrophil and eosinophil counts. Variations in erythrocyte counts were sometimes statistically significant but they were moderate and no circadian rhythm was evident. Thus, examinations of the rat blood picture during biomedical studies have to be related to the pertinent time of circadian clocks and in long-term studies also to the time of season.

Animals↗

Neural compensation for mechanical loading of the hand during coupled oscillations of the hand and foot.

The role of kinaesthetic afferences in controlling coupling of voluntary oscillation of the hand and foot, both in-phase and anti-phase, was investigated by modifying the mechanical properties of one of the two segments (the hand) with applied inertial or elastic loads. Loads consisted of a lead disk, rotating coaxially with the wrist (total inertial momentum 15 g m2), or in two symmetrical rubber bands (elasticity, 4 g deg(-1)) connected 5 cm away from the wrist pivot. Experiments were performed on five male and five female subjects. Both the frequency responses of the hand and foot (i.e. the phase relations between the onset of muscular activation in limb extensors and the onset of the related movement) and the inter-limb phase relations (the phase differences between the hand and foot movement cycles and between the onsets of the electromyographic (EMG) activity in hand and foot extensors) were analysed. The hand frequency-response was fitted with a 2nd-order model, allowing us to describe the loaded and unloaded conditions through the changes in the model response. Inertial loading induced an immediate and steep decay in the frequency response, with a clear-cut reduction of the model resonance frequency, while elastic loading shifted the response to the right and upwards. Inter-limb phase relations were only partially affected by inertial loading of the hand. Despite the fact that the load strongly increased the difference between the frequency-responses of the hand and foot, when hand and foot were oscillated in-phase only about half of this difference remained as an increased phase-lag between hand and foot oscillations. The other half was offset by an advance of the contraction of the hand movers with respect to the foot movers. This compensation mechanism was more effective during anti-phase than during in-phase movements. Elastic loading improved inter-limb synchronisation, since it superimposed the hand frequency-response on that of the foot. In this condition, the requested synchronisation (in-phase or anti-phase) could be achieved by an almost simultaneous (or in strict phase opposition) contraction of the hand and foot movers. In conclusion, the main feedback reaction to the de-coupling effect of hand loading consisted in modifying the timing of activation of the muscles moving the extremities. An advance of hand movers on foot movers is already present in unloaded conditions to compensate for the difference in the natural mechanical properties of the two segments. This advance is enhanced when increasing the inertia of the hand system and attenuated when increasing its elasticity.

Adaptation, Physiological↗

[Physical time and personal biological time in gerontologic research].

Beside the reversible t-time of physics is introduced an irreversible logarithmical tau-time as a second time. This time is determined by growth, vitality, and reliability of an organism. Using the tau-time it is possible to divide the lifespan of an organism into four parts. Each segment is of approximately the same duration, namely a quarter of the lifespan. There is an analogy between tau-time and physical entropy.

Aged↗

Photodynamic therapy with verteporfin for anterior segment neovascularizations in neovascular glaucoma.

PURPOSE: To evaluate photodynamic therapy (PDT) with verteporfin for iris and angle neovascularization in eyes with neovascular glaucoma. DESIGN: Interventional case series. METHODS: A prospective, noncomparative case series included four patients (four eyes) with neovascular glaucoma. PDT was performed following the parameters of treatment of age-related macular degeneration with photodynamic therapy Study Group (TAP). The laser was directed at the anterior chamber angle and iris surface using a Goldmann three-mirror contact lens. Iris and angle neovascularization were quantified using the number of clock hours involved. Outcome measures were obliteration of neovascularization and decrease of intraocular pressure (IOP). RESULTS: One week after PDT, we registered complete obliteration of angle neovascularization and partial occlusion of iris neovascularization. Subsequent reopening of angle neovascularization was detectable at 1 month. Intraocular pressure diminished considerably after 1 week, with a subsequent tendency toward stabilization. CONCLUSIONS: Photodynamic therapy can be used safely and effectively in the early phases of neovascular glaucoma to achieve angle neovascularization obliteration and IOP reduction.

Adult↗

Spinal source for the synchronous fluctuations of bilateral monosynaptic reflexes in cats.

Successive stimuli of constant intensity applied to Ia afferents produce spinal monosynaptic reflexes (MSRs) of variable amplitude. We recorded simultaneous MSRs in the left and right L7 (or L6) ventral roots of anesthetized cats. We analyzed the cross-covariance (CCV) between the amplitudes of bilateral MSRs. Long-time series (5 to 8 h) of these bilateral MSRs exhibited transitory changes in their covariations (as measured by the zero-lag peak of their CCV), thus suggesting the existence of certain neural sources contributing to produce these changes. The aim of the present study was to show that spinal centers producing negative spontaneous cord dorsum potentials (nSCDPs) contribute to maintain correlations in the amplitude of bilateral MSRs. After spinal cord transection at the L1 segment, no significant changes were observed in the correlation between the amplitude of bilateral nSCDPs versus the amplitude of bilateral MSRs. However, this correlation, as well as the peak at zero lag in the CCV between bilateral MSRs and the CCV between bilateral nSCDPs, respectively, were abolished after a subsequent longitudinal bisection at the L1-S2 spinal segments. These results suggest that lumbar spinal neurons (bilaterally interconnected) contribute to maintain the synchronous fluctuations of bilateral MSRs.

Animals↗

Modulation of pacemaker activity by IPSP and brief length perturbations in the crayfish stretch receptor.

We have studied the influences of brief stretches and releases and of inhibitory postsynaptic potentials (IPSPs) on pacemaker activity of the crayfish stretch receptor (RM1). Stimuli shift or reset the ongoing rhythm. Resettings were different if evaluated in interspike intervals containing perturbations, or in succeeding ones, and are referred to as early and late, respectively. Early resetting revealed that stretches and releases or IPSPs advance and delay, respectively, the next spike. With small stretches and releases or IPSPs, effects depend on the timing of the perturbation relative to the previous spike or phase, but above a characteristic mechanical perturbation amplitude the next spike fires at a fixed latency, invariant with the phase. Of particular interest was the finding that during late resetting the first successive intervals following stretches and releases or IPSPs were longer and shorter, respectively, than the period. This led, in approximately 50% of the cases, to a gradual recovery of the original pacemaker beat in the sense that spikes fire timed as if the early rhythm shift had not occurred. In conclusion, the recent firing history is essential in determining the RM1's response. The receptor's sensitivity is a complex nonlinear and periodic function of the pacemaker activity, and the response is due to interactions between pacemaker- and perturbation-induced transmembrane ionic currents. Although several alternative mechanisms may underly beat recovery, the results suggest that at least two coupled oscillators, one perturbable and the other not, provide a better explanation than a single oscillator. The physiological significance of resettings is unknown, but the early rhythm shift may synchronize RM1s in several segments when the animal's tail is moved, and conversely recovery would reduce synchrony, with obvious influences on shared postsynaptic neurons.

Animals↗

Ultrasound biomicroscopic findings in a case of cyclodialysis.

Ultrasound biomicroscopy (UBM) with a high frequency can be used to evaluate the structure of the anterior eye segment in vivo. A 24-year-old male was referred to us after 1 month of follow-up by a local ophthalmologist, because of decreased visual acuity and hypotony after a blunt eye injury. A cyclodialysis cleft in the 2- to 4-o'clock position and a cavernous pattern all over the choroid were found using UBM. The patient underwent surgical treatment to close the cleft. Even after the recovery of intraocular pressure (IOP), the peripheral ciliary body around 360 degrees was still separated from the sclera when examined by UBM. Despite the detached ciliary body, keeping IOP within normal levels is an interesting finding. UBM is helpful in the diagnosis and treatment of traumatic cyclodialysis.

Adult↗

Molecular systematics of the Hyaenidae: relationships of a relictual lineage resolved by a molecular supermatrix.

The four extant species of hyenas (Hyaenidae; Carnivora) form a morphologically and ecologically heterogeneous group of feliform carnivorans that are remnants of a formerly diverse group of mammalian predators. They include the aardwolf (Proteles cristatus), a termite-feeding specialist, and three species with a craniodental morphology adapted to cracking the bones of prey and/or carcasses, the spotted hyena (Crocuta crocuta), brown hyena (Parahyaena brunnea), and striped hyena (Hyaena hyaena). Hyenas have been the subject of a number of systematic studies during the last two centuries, due in large part to the extensive fossil record of the group, with nearly 70 described fossil species. Morphological studies incorporating both fossil and living taxa have yielded different conclusions regarding the evolutionary relationships among living hyenas. We used a molecular supermatrix comprised of seven nuclear gene segments and the complete mitochondrial cytochrome b gene to evaluate phylogenetic relationships among the four extant hyaenid species. We also obtained sequence data from representative species of all the main families of the Feliformia (Felidae, Herpestidae, and Viverridae) to estimate the sister group of the Hyaenidae. Maximum parsimony and maximum likelihood analyses of the supermatrix recovered identical topologies. Furthermore, Bayesian phylogenetic analyses of the supermatrix, with among-site rate variation among data partitions parameterized in three different ways, also yielded the same topology. For each phylogeny reconstruction method, all but two nodes received 100% bootstrap or 1.00 posterior probability nodal support. Within the monophyletic Hyaenidae, Parahyaena and Hyaena were joined together, with Crocuta as the sister to this clade, and Proteles forming the most basal lineage. A clade containing two species of mongoose (core Herpestidae) plus Cryptoprocta ferox (currently classified in Viverridae) was resolved as the sister group of Hyaenidae. The pattern of relationships among the three bone-cracking hyaenids (Crocuta, Hyaena, and Parahyaena) is incongruent with recent cladistic assessments based on morphology and suggests the need to reevaluate some of the morphological characters that have been traditionally used to evaluate relationships among hyenas. Divergence time estimates based on a Bayesian relaxed molecular clock indicates that hyaenids diverged from their feliform sister group 29.2 MYA, in the Middle Oligocene. Molecular clock estimates also suggest that the origin of the aardwolf is much more recent (10.6 MYA) than that implied by a cladistic analysis of morphology ( approximately 20 MYA) and suggests that the aardwolf is possibly derived from a bone and meat eating lineage of hyaenids that were present in the Late Miocene. [Hyaenidae; phylogeny; cytochrome b; nuclear gene segments; Proteles; Crocuta; Hyaena; Parahyaena.].

Animals↗

Age effects on anorectal pressure in anal continent women with lower urinary tract dysfunction.

The objective of this paper is to evaluate age and associated factors affecting anorectal pressure profilometry in anal-continent women with lower urinary tract symptoms. One hundred and ten anal-continent women (mean age, 47.7+/-12.8 years; range, 23-87 years) with lower urinary tract symptoms voluntarily participated in this study after undergoing a complete urogynecological evaluation including a multichannel urodynamic study. Anorectal pressure was evaluated by using a radial four-channel manometry with a water-filled catheter, which was placed 10 cm into the anorectum above the anal verge. We divided the anorectal pressure profile into five segments and four axes to clarify the axis-specific defect or site-specific damage in the sphincter profile. The aging process had a negative effect on the peak resting pressure from the 41 to 100th percentile of the anorectal pressure profile at 12 o'clock, 3 o'clock, and 6 o'clock (P<0.05). With voluntary squeezing, aging had negative effects on the peak squeeze pressure from the 41 to 100th percentile of the anorectal pressure profile at 3 o'clock, and 61 to 80 percentile at 12 o'clock (P<0.05). There is a trend where anorectal pressure reduces as a woman ages, especially at the anal sphincter area in women with lower urinary tract symptoms. The anterior and left sides of the anorectal sphincter seem to be the most vulnerable in the aging process.

Adult↗

Anterior segment changes in rabbits after experimental aqueous replacement with various amounts of different perfluorocarbon liquids.

BACKGROUND: We evaluated biomicroscopic and histological effects on the anterior segment in the rabbit eye after temporary aqueous substitution with various amounts (0.2 cc and 0.025 cc) of perfluorodecaline (PFD) and perfluorophenanthrene (PFP). METHODS: A quantity of 0.2 cc of the two perfluorocarbon (PFC) liquids was exchanged simultaneously with about 50% of the aqueous in 15 rabbit eyes each for periods of 1, 2, or 4 weeks. At these points some eyes were enucleated for histological examination. After 2 and 4 weeks the substances were removed from the remaining eyes, which were then followed up for 8-10 weeks. In an additional 8 eyes, 0.025 cc PFD or PFP was injected and left for 8 weeks. Four eyes received balanced salt solution and served as controls. Beside biomicroscopic evaluation and measurement of the intraocular pressure, endothelial cell counts and corneal pachymetry were performed regularly during follow-up. RESULTS: The postoperative results were well comparable for PFD and PFP eyes. Within the first 2 weeks postoperatively corneal edema with endothelial cell loss was observed in both groups. Thereafter regression of the edema started independently of whether the substances were removed or not. IOP was not elevated at any time. At the end of follow-up central corneal thickness was the same as initially. In the inferior corneal endothelium cell density decreased to 45-50% of that in normals. Histologically, vacuoles in the iris and chamber angle were found inferiorly after 4 weeks. Chamber angle closures were present between 5 and 7 o'clock in those eyes where the PFC liquids had been removed after 2 and 4 weeks. Eyes with 0.025 cc PFD or PFP droplets showed vacuolization of the inferior trabecular meshwork 8 weeks postoperatively that was comparable with eyes which had a 50% aqueous replacement for 4 weeks. Control eyes remained unchanged in all aspects. CONCLUSION: Anterior segment damage caused by PFC liquids is a contact-dependent effect seen in the early observation period. Experimentally there was no difference between the products used or between 2 and 4 weeks' duration of the tamponade.

Animals↗

Experimental vitreous and aqueous replacement with perfluorophenanthrene. Clinical, histologic, and electrophysiologic results.

PURPOSE: Anterior and posterior segment changes of experimental vitreous and aqueous substitution with Perfluorophenanthrene were evaluated. METHODS: In 28 rabbit eyes that underwent vitrectomy, tamponades of 1.2 cc Perfluorophenanthrene remained as long as 8 weeks under clinical and electrophysiologic control. Histologic examinations of the eyes were done 1, 2, 4, and 8 weeks after insertion of the tamponade. In an additional 15 rabbit eyes, Perfluorophenanthrene was injected into the anterior chamber, and in some cases it was removed after 2 and 4 weeks, respectively. Follow-up examinations, which were done no later than 12 weeks after injection, included clinical appearance, endothelial cell counts, corneal pachymetry, tonometry, and histopathology. RESULTS: Histologically we found narrowing of the outer plexiform layer and single macrophages in the inferior retina after 2 weeks. Cell loss in the outer nuclear layer and wrinkling of the outer retinal layers were observed after 4 weeks, which lead to the development of irregularities of all layers inferiorly after 8 weeks. Electroretinograms showed unchanged b-wave amplitudes after maximal light stimulation at each examination, but separate interpretation of low light intensity responses showed a significant decrease in b-wave amplitudes 4 weeks after surgery. Anterior segment intolerance started with stromal edema on the second day after surgery; corneal vascularization and scar formation occurred subsequently. Inferior endothelial cell density decreased to about 50%. Histologically inflammatory reactions, vacuolization of the inferior trabecular meshwork, and closure of the chamber angle between 5 and 7 o'clock were observed. CONCLUSIONS: Perfluorophenanthrene is only suitable for very short-term vitreous replacement unless prolapsing into the anterior chamber. Damages to the retina were observed 2 weeks after surgery.

Animals↗

Interaction of the Circadian Cycle with the Cell Cycle in Pyrocystis fusiformis.

Dividing pairs or single cells of the large dinoflagellate, Pyrocystis fusiformis Murray, were isolated in capillary tubes and their morphology was observed over a number of days, either in a light-dark cycle or in constant darkness. Morphological stages were correlated with the first growth stage, G(1), DNA synthesis, S, the second growth stage, G(2), mitosis, M, and cytokinesis, C, segments of the cell division cycle. The S phase was identified by measuring the nuclear DNA content of cells of different morphologies by the fluorescence of 4', 6-diamidino-2-phenylindole dichloride.Cells changed from one morphological stage to the next only during the night phase of the circadian cycle, both under light-dark conditions and in continuous darkness. Cells in all segments of the cell division cycle displayed a circadian rhythm in bioluminescence. These findings are incompatible with a mechanism for circadian oscillations that invokes cycling in G(q), an hypothesized side loop from G(1). All morphological stages, not only division, appear to be phased by the circadian clock.

Journal Article↗

Two-year corneal endothelial cell assessment following INTACS implantation.

PURPOSE: To evaluate the 2-year effects of intrastromal corneal ring segments (INTACS) on the corneal endothelium. METHODS: Non-contact specular microscopy was performed as a subgroup test in a Phase III clinical trial. Endothelial cell images were collected before surgery and at 6, 12, and 24 months after surgery at the central and peripheral (6 and 10 o'clock) regions. Images were recorded and analyzed later by a central reading center. Cell density, coefficient of variation, and percent hexagonal cells were determined. RESULTS: There were no clinically significant changes in the endothelial cell structure at 6, 12, and 24 months (102 eyes). There was a gain of 5 cells/mm2 (6 months) and 3 cells/mm2 (12 months) at the central region of the cornea and a loss of 28 cells/mm2 at 24 months. At the 6 o'clock region of the cornea, there was a loss of 0, 24, and 92 cells/mm2 at 6, 12, and 24 months. At the 10 o'clock region of the cornea, there was a loss of 14, 30, and 94 cells/mm2 at 6, 12, and 24 months. INTACS did not statistically affect the central cell density at 6 and 12 months, however, there was a slight loss centrally at 24 months. At 24 months, all corneal regions had a slight decrease in cell density. In all eyes, mean central and peripheral endothelial cell counts remained above 2495 cells/mm2. Coefficient of variation improved and percent hexagonal cells remained unchanged. CONCLUSION: Endothelial cell density changes at 2 years after INTACS implantation were not clinically significant and endothelial cell remodeling was present.

Adult↗

Scheimpflug biometry of the anterior segment after implantation of foldable iris-fixated lenses.

PURPOSE: To evaluate intraocular dimensions of the anterior segment of myopic phakic eyes after implantation of foldable iris-fixated lenses. METHODS: Seventeen myopic eyes that received a foldable iris-fixated phakic intraocular lens (PIOL) were assessed. Distances between the cornea and the IOL-optic edge and between the IOL optic and the crystalline lens were evaluated using Scheimpflug photography 3 months postoperatively. RESULTS: The average postoperative distance between the central corneal endothelium and the anterior surface of the IOL was 2.01 +/- 0.26 mm. The distance between the corneal endothelium and the peripheral edge of the IOL averaged 1.32 +/- 0.18 mm at the 12 o'clock position and 1.34 +/- 0.21 mm at the 6 o'clock position. The distance between the crystalline lens and the posterior surface of the IOL averaged 0.73 +/- 0.09 mm. CONCLUSIONS: The high quality of the three-dimensional Scheimpflug images allowed measurements of intraocular distances in PIOL implanted eyes. Distances between the foldable iris-fixated IOL and crucial surrounding tissues could be determined 3 months postoperatively.

Adult↗

Onset of gastrulation, morphogenesis and somitogenesis in mouse embryos displaying compensatory growth.

This is a study on the ability of mouse embryos to compensate for a loss of cells and to develop with body parts of normal size and normal proportions during post-implantation development. Micro-manipulations were performed on 4-cell pre-implantation mouse embryos to reduce the number of cells by 25% (3/4 embryos) or 50% (2/4 embryos). Blastocysts developed from these embryos showed a preferential loss of inner cell mass population, and fewer of them formed viable embryos after implantation. The size of post-implantation 3/4 embryos was initially smaller than controls of the same gestational age, but compensatory growth, achieved by increasing cell numbers at above the normal rate and beyond the normal duration, took place between 6.5 and 11.5 days, resulting in a complete restoration of body size. During compensatory growth the 3/4 embryos rescheduled events of gastrulation and morphogenesis in keeping with cell number or body size appropriate for each developmental stage. The formation of the correct number of somites was accomplished by changing the rate of somite segmentation and by an adjustment of the size of individual somites and somitomeres proportional to the available amount of precursor tissues. Morphogenesis and pattern formation in embryos recovering from earlier cell losses are therefore regulated in accordance to tissue volume (or cell number) instead of chronological age or some intrinsic cellular clock.

Animals↗

A compositional segmentation of the human mitochondrial genome is related to heterogeneities in the guanine mutation rate.

We applied a hidden Markov model segmentation method to the human mitochondrial genome to identify patterns in the sequence, to compare these patterns to the gene structure of mtDNA and to see whether these patterns reveal additional characteristics important for our understanding of genome evolution, structure and function. Our analysis identified three segmentation categories based upon the sequence transition probabilities. Category 2 segments corresponded to the tRNA and rRNA genes, with a greater strand-symmetry in these segments. Category 1 and 3 segments covered the protein- coding genes and almost all of the non-coding D-loop. Compared to category 1, the mtDNA segments assigned to category 3 had much lower guanine abundance. A comparison to two independent databases of mitochondrial mutations and polymorphisms showed that the high substitution rate of guanine in human mtDNA is largest in the category 3 segments. Analysis of synonymous mutations showed the same pattern. This suggests that this heterogeneity in the mutation rate is partly independent of respiratory chain function and is a direct property of the genome sequence itself. This has important implications for our understanding of mtDNA evolution and its use as a 'molecular clock' to determine the rate of population and species divergence.

Algorithms↗

Photorefractive keratectomy after intrastromal corneal ring segment explantation.

PURPOSE: To describe a case of photorefractive keratectomy after removal of intrastromal corneal ring segments from the cornea. METHODS: During United States Food and Drug Administration Phase III Trials for intrastromal corneal ring segments (ICRS), the implanted segments were removed from the cornea of the right eye of a patient because of dissatisfaction with glare, halos, and fluctuating vision. Ten months after ICRS explantation, the-patient underwent a photorefractive keratectomy procedure to the same eye. RESULTS: One month after removal of the ICRS, the patient's manifest refraction was within +/- 0.50 diopters of his original manifest refraction. Photorefractive keratectomy was planned to the same eye 6 months later. At the first attempt, the epithelium could not be removed with the laser and scrape technique, and residual epithelium was noted at the vertical meridian (12 o'clock) corneal incision site, which had been used for ICRS surgery and explant; therefore, the procedure was aborted. At the second attempt, with a mechanical epithelial brush (AMOILS Epithelial Scrubber; Innova, Inc, Toronto, Canada), the epithelium was removed with ease. After this, photorefractive keratectomy was done without difficulty or complication. At his most recent 8-month postphotorefractive keratectomy examination, the patient had an uncorrected visual acuity of RE: 20/16, with a manifest refraction of -0.75 to 0.75 x 170 degrees, a faint haze at the site of the stromal channel, and a small scar at the incision site on slit-lamp examination. CONCLUSIONS: Intrastromal corneal ring segments can be readily removed from the cornea, if required. In this case, the refraction returned to its preoperative state soon after the explant procedure and remained stable over time. Photorefractive keratectomy was performed as a secondary refractive surgical procedure after the removal of ICRS without difficulty or complication. However, removal of the epithelium is probably best accomplished with the use of an epithelial brush, considering the changes in the epithelial adherence in a postsurgical cornea. Further studies are required to establish the safety and efficacy of secondary refractive surgical procedures after ICRS explantation.

Adult↗