The type-A horizontal cell: GABAergic characteristics and role in development of the outer plexiform layer

Morphological analysis of neonatal rabbit retina suggests that the type-A horizontal cell acts as the pioneer cell for development of the OPL. It is the first mature element of the OPL, and it forms the infrastructure upon which the OPL accrues. The role of type-A horizontal cells in influencing postnatal development of the OPL was examined.^ GABAergic characteristics of the type-A horizontal cell were defined. The type-A horizontal cell was found to possess two more GABAergic characteristics in addition to those previously demonstrated, during a short period in early postnatal development: endogenous stores of GABA and the GABA precursor, glutamate. Lesioning the type-A horizontal cell resulted in their permanent loss in addition to the disappearance of cone terminals and a dramatic increase in rod terminals within the OPL. Thus the type-A cells are not a necessary prerequisite for positioning the OPL in postnatal development, but may be necessary for establishment of the normal photoreceptor mosaic.^ Since type-A horizontal cells possess a number of GABAergic qualities during the period of cone photoreceptor cell differentiation, and there are reports of GABA's trophic action in other developing neuronal systems; the role that GABAergic type-A horizontal cells play in directing photoreceptor differentiation was examined.^ Disrupting effects of GABA-A receptor antagonists indicate that type-A horizontal cells act as postsynaptic targets for the growing cone terminals of photoreceptor cells. These trophic or synaptic interactions may involve GABA-A receptors activated by GABA released from horizontal cells. These findings are consistent with the hypothesis that type-A horizontal cells act as pioneering cells in directing the postnatal development of the OPL.^ These studies offer an in depth analysis of the structural and chemical relationship between type-A horizontal cells and other elements of the OPL from which the roles of type-A horizontal cells and the GABA system in development can be defined. They contribute to our knowledge of both structural and GABAergic mechanisms involved in central nervous system development. ^

Fetal lungs of tenascin-C-deficient mice grow well, but branch poorly in organ culture

Tenascin-C (TNC) is a multidomain extracellular matrix protein that contributes to organogenesis and tumorgenesis. To elucidate its developmental function in the context of TNC deficiency, lung lobes of TNC null mice were obtained at Embryonic Days E11.5 and E12.5 and cultured for 3 d. In lung explants of homozygote TNC-deficient embryos (E12.5) the number of future airway branches was reduced by 36% as compared with wild-type. In heterozygote explants only half of the reduction (18%) was observed. No significant alteration, neither of the explant growth nor of the pattern of airway branching, was noticed in TNC-null explants. However, the terminal endbuds of the transgenic explants were enlarged. The results are supported by a morphologic investigation at Postnatal Day P2, where the airspaces of TNC-deficient lungs appeared larger than in wild-type lungs. Taken together, our results represent the first developmental phenotype of TNC-null mice. We conclude that TNC takes part in the control of fetal lung branching, and that not only the presence of TNC but also its amount is important. Because TNC is predominantly expressed at the growing tip of the future airways, we hypothesize that TNC promotes the penetration into the surrounding mesenchyme and the branching of the growing airways.

Polar MM5 Simulations of the Winter Climate of the Laurentide Ice Sheet at the LGM

Optimized regional climate simulations are conducted using the Polar MM5, a version of the fifth-generation Pennsylvania State University-NCAR Mesoscale Model (MM5), with a 60-km horizontal resolution domain over North America during the Last Glacial Maximum (LGM, 21 000 calendar years ago), when much of the continent was covered by the Laurentide Ice Sheet (LIS). The objective is to describe the LGM annual cycle at high spatial resolution with an emphasis on the winter atmospheric circulation. Output from a tailored NCAR Community Climate Model version 3 (CCM3) simulation of the LGM climate is used to provide the initial and lateral boundary conditions for Polar MM5. LGM boundary conditions include continental ice sheets, appropriate orbital forcing, reduced CO2 concentration, paleovegetation, modified sea surface temperatures, and lowered sea level. Polar MM5 produces a substantially different atmospheric response to the LGM boundary conditions than CCM3 and other recent GCM simulations. In particular, from November to April the upper-level flow is split around a blocking anticyclone over the LIS, with a northern branch over the Canadian Arctic and a southern branch impacting southern North America. The split flow pattern is most pronounced in January and transitions into a single, consolidated jet stream that migrates northward over the LIS during summer. Sensitivity experiments indicate that the winter split flow in Polar MM5 is primarily due to mechanical forcing by LIS, although model physics and resolution also contribute to the simulated flow configuration. Polar MM5 LGM results are generally consistent with proxy climate estimates in the western United States, Alaska, and the Canadian Arctic and may help resolve some long-standing discrepancies between proxy data and previous simulations of the LGM climate.

Debris discs around M stars: non-existence versus non-detection

Motivated by the reported dearth of debris discs around M stars, we use survival models to study the occurrence of planetesimal discs around them. These survival models describe a planetesimal disc with a small number of parameters, determine if it may survive a series of dynamical processes and compute the associated infrared excess. For the Wide-field Infrared Survey Explorer (WISE) satellite, we demonstrate that the dearth of debris discs around M stars may be attributed to the small semimajor axes generally probed if either: (1) the dust grains behave like blackbodies emitting at a peak wavelength coincident with the observed one; (2) or the grains are hotter than predicted by their blackbody temperatures and emit at peak wavelengths that are shorter than the observed one. At these small distances from the M star, planetesimals are unlikely to survive or persist for time-scales of 300 Myr or longer if the disc is too massive. Conversely, our survival models allow for the existence of a large population of low-mass debris discs that are too faint to be detected with current instruments. We gain further confidence in our interpretation by demonstrating the ability to compute infrared excesses for Sun-like stars that are broadly consistent with reported values in the literature. However, our interpretation becomes less clear and large infrared excesses are allowed if only one of these scenarios holds: (3) the dust grains are hotter than blackbody and predominantly emit at the observed wavelength; (4) or are blackbody in nature and emit at peak wavelengths longer than the observed one. Both scenarios imply that the parent planetesimals reside at larger distances from the star than inferred if the dust grains behaved like blackbodies. In all scenarios, we show that the infrared excesses detected at 22 μm (via WISE) and 70 μm (via Spitzer) from AU Mic are easily reconciled with its young age (12 Myr). Conversely, the existence of the old debris disc (2–8 Gyr) from GJ 581 is due to the large semimajor axes probed by the Herschel PACS instrument. We elucidate the conditions under which stellar wind drag may be neglected when considering dust populations around M stars. The WISE satellite should be capable of detecting debris discs around young M stars with ages ∼10 Myr.

Horizontal ridge augmentation in conjunction with or prior to implant placement in the anterior maxilla: a systematic review.

PURPOSE To systematically review clinical studies examining the survival and success rates of implants in horizontal ridge augmentation, either prior to or in conjunction with implant placement in the anterior maxilla. MATERIALS AND METHODS A literature search was undertaken up to September 2012 including clinical studies in English with ≥ 10 consecutively treated patients and a mean follow-up of at least 12 months. Two reviewers screened the pertinent articles and extracted the data. Key words focused on the outcome parameters (implant success, implant survival, horizontal bone gain, and intra- and postoperative complications) in studies utilizing either a simultaneous approach (ridge augmentation performed at the time of implant placement) or a staged approach (ridge augmentation performed prior to implant placement) were analyzed. RESULTS A total of 13 studies met the inclusion criteria, with 2 studies in the simultaneous group and 11 studies in the staged group. In the simultaneous group, survival rates of implants were 100% in both studies, with one study also reporting a 100% implant success rate. No data on horizontal bone gain were available. In the staged group, success rates of implants placed in horizontally augmented ridges ranged from 96.8% to 100% (two studies), and survival rates ranged from 93.5% to 100% (five studies). However, follow-up periods differed widely (up to 4.1 years). Mean horizontal bone gain determined at reentry (implant placement) ranged from 3.4 to 5.0 mm with large overall variations (0 to 9.8 mm, five studies). Intraoperative complications were not reported. Postsurgical complications included mainly mucosal dehiscences (five studies), and, occasionally, complete failures of block grafts were described in one study. CONCLUSIONS Staged and simultaneous augmentation procedures in the anterior maxilla are both associated with high implant success and survival rates. The level of evidence, however, is better for the staged approach than for the simultaneous one.

Horizontal head titubation in infants with Joubert syndrome: a new finding

AIM Head thrusts are well documented in Joubert syndrome and ocular motor apraxia. We provide a detailed clinical characterization of head titubation in 13 young children with Joubert syndrome. METHOD Detailed characterization of head titubation was assessed by targeted clinical evaluation and/or analysis of videos. RESULTS In 12 of 13 children (eight males, five females; median age 6y, range 2mo-15y) head titubation was first recognized in the first 2 months of age and decreased in severity until spontaneous resolution. In all children, the head titubation was horizontal, high frequency (~3Hz), had small amplitude (5-10°), was never present during sleep, and did not interfere with the neurodevelopment during infancy. In the majority of children, emotion, anxiety, and tiredness were worsening factors for head titubation. INTERPRETATION Head titubation is a benign, early presentation of Joubert syndrome. Head titubation in hypotonic infants should prompt a careful search for Joubert syndrome. Awareness of its occurrence in Joubert syndrome may avoid unnecessary investigations.

Dissecting abdominal aortic aneurysm in Ang II-infused mice: suprarenal branch ruptures and apparent luminal dilatation.

AIMS In this work, we provide novel insight into the morphology of dissecting abdominal aortic aneurysms in angiotensin II-infused mice. We demonstrate why they exhibit a large variation in shape and, unlike their human counterparts, are located suprarenally rather than infrarenally. METHODS AND RESULTS We combined synchrotron-based, ultra-high resolution ex vivo imaging (phase contrast X-Ray tomographic microscopy) with in vivo imaging (high-frequency ultrasound and contrast-enhanced micro-CT) and image-guided histology. In all mice, we observed a tear in the tunica media of the abdominal aorta near the ostium of the celiac artery. Independently we found that, unlike the gradual luminal expansion typical for human aneurysms, the outer diameter increase of angiotensin II-induced dissecting aneurysms in mice was related to one or several intramural haematomas. These were caused by ruptures of the tunica media near the ostium of small suprarenal side branches, which had never been detected by the established small animal imaging techniques. The tear near the celiac artery led to apparent luminal dilatation, while the intramural haematoma led to a dissection of the tunica adventitia on the left suprarenal side of the aorta. The number of ruptured branches was higher in those aneurysms that extended into the thoracic aorta, which explained the observed variability in aneurysm shape. CONCLUSION Our results are the first to describe apparent luminal dilatation, suprarenal branch ruptures, and intramural haematoma formation in dissecting abdominal aortic aneurysms in mice. Moreover, we validate and demonstrate the vast potential of phase contrast X-ray tomographic microscopy in cardiovascular small animal applications.

Reading performance is not affected by a prism induced increase of horizontal and vertical vergence demand

PURPOSE Dyslexia is the most common developmental reading disorder that affects language skills. Latent strabismus (heterophoria) has been suspected to be causally involved. Even though phoria correction in dyslexic children is commonly applied, the evidence in support of a benefit is poor. In order to provide experimental evidence on this issue, we simulated phoria in healthy readers by modifying the vergence tone required to maintain binocular alignment. METHODS Vergence tone was altered with prisms that were placed in front of one eye in 16 healthy subjects to induce exophoria, esophoria, or vertical phoria. Subjects were to read one paragraph for each condition, from which reading speed was determined. Text comprehension was tested with a forced multiple choice test. Eye movements were recorded during reading and subsequently analyzed for saccadic amplitudes, saccades per 10 letters, percentage of regressive (backward) saccades, average fixation duration, first fixation duration on a word, and gaze duration. RESULTS Acute change of horizontal and vertical vergence tone does neither significantly affect reading performance nor reading associated eye movements. CONCLUSION Prisms in healthy subjects fail to induce a significant change of reading performance. This finding is not compatible with a role of phoria in dyslexia. Our results contrast the proposal for correcting small angle heterophorias in dyslexic children.

Investigation of retinal morphology alterations using spectral domain optical coherence tomography in a mouse model of retinal branch and central retinal vein occlusion.

Retinal vein occlusion is a leading cause of visual impairment. Experimental models of this condition based on laser photocoagulation of retinal veins have been described and extensively exploited in mammals and larger rodents such as the rat. However, few reports exist on the use of this paradigm in the mouse. The objective of this study was to investigate a model of branch and central retinal vein occlusion in the mouse and characterize in vivo longitudinal retinal morphology alterations using spectral domain optical coherence tomography. Retinal veins were experimentally occluded using laser photocoagulation after intravenous application of Rose Bengal, a photo-activator dye enhancing thrombus formation. Depending on the number of veins occluded, variable amounts of capillary dropout were seen on fluorescein angiography. Vascular endothelial growth factor levels were markedly elevated early and peaked at day one. Retinal thickness measurements with spectral domain optical coherence tomography showed significant swelling (p<0.001) compared to baseline, followed by gradual thinning plateauing two weeks after the experimental intervention (p<0.001). Histological findings at day seven correlated with spectral domain optical coherence tomography imaging. The inner layers were predominantly affected by degeneration with the outer nuclear layer and the photoreceptor outer segments largely preserved. The application of this retinal vein occlusion model in the mouse carries several advantages over its use in other larger species, such as access to a vast range of genetically modified animals. Retinal changes after experimental retinal vein occlusion in this mouse model can be non-invasively quantified by spectral domain optical coherence tomography, and may be used to monitor effects of potential therapeutic interventions.

Enhanced-depth optical coherence tomography for imaging horizontal rectus muscles in Graves' orbitopathy.

PURPOSE Graves' orbitopathy (GO) is an extraocular eye disease with symptoms ranging from minor discomfort from dry eyes to strabismus and visual loss. One of the hallmarks of active GO is visible hyperemia at the insertion of the extraocular muscles. The aim of the present study was to evaluate the use of enhanced-depth imaging spectral domain anterior segment optical coherence tomography (EDI SD AS-OCT) for detecting pathological changes in horizontal recti muscles of patients with GO. METHODS Prospective cross sectional study of 27 eyes. Only women were included. EDI AS-OCT was used to measure the thickness of the tendons of the horizontal recti muscles in a predefined area in patients with GO and healthy controls. RESULTS EDI AS-OCT was able to image the tendons of the horizontal recti muscles in both healthy controls and patients suffering from GO. The mean thickness of the medial rectus muscle (MR) tendon was 256.4 μm [±17.13 μm standard deviation (SD)] in the GO group and, therefore, significantly thicker (p = 0.046) than in the healthy group which had a mean thickness of 214.7 μm (±5.516 μm SD). There was no significant difference in the mean thickness of the tendon of the lateral recti muscles (LRs) between these groups. CONCLUSION This is the first report showing that EDI AS-OCT is suitable to detect swelling at the insertion site of the MR muscle in GO. MR tendon thickness may be a useful parameter to monitor activity in these patients.

Vertical and Horizontal Vegetation Structure across Natural and Modified Habitat Types at Mount Kilimanjaro

In most habitats, vegetation provides the main structure of the environment. This complexity can facilitate biodiversity and ecosystem services. Therefore, measures of vegetation structure can serve as indicators in ecosystem management. However, many structural measures are laborious and require expert knowledge. Here, we used consistent and convenient measures to assess vegetation structure over an exceptionally broad elevation gradient of 866–4550m above sea level at Mount Kilimanjaro, Tanzania. Additionally, we compared (human)-modified habitats, including maize fields, traditionally managed home gardens, grasslands, commercial coffee farms and logged and burned forests with natural habitats along this elevation gradient. We distinguished vertical and horizontal vegetation structure to account for habitat complexity and heterogeneity. Vertical vegetation structure (assessed as number, width and density of vegetation layers, maximum canopy height, leaf area index and vegetation cover) displayed a unimodal elevation pattern, peaking at intermediate elevations in montane forests, whereas horizontal structure (assessed as coefficient of variation of number, width and density of vegetation layers, maximum canopy height, leaf area index and vegetation cover) was lowest at intermediate altitudes. Overall, vertical structure was consistently lower in modified than in natural habitat types, whereas horizontal structure was inconsistently different in modified than in natural habitat types, depending on the specific structural measure and habitat type. Our study shows how vertical and horizontal vegetation structure can be assessed efficiently in various habitat types in tropical mountain regions, and we suggest to apply this as a tool for informing future biodiversity and ecosystem service studies.

Anterior superior alveolar nerve (ASAN): A morphometric-anatomical Analysis

The anterior superior alveolar nerve (ASAN) is a branch of the infraorbital nerve. Only few studies have morphometrically evaluated the course of the ASAN. Midfacial segments of ten hemisectioned fresh adult cadaver heads were dissected to uncover the anterior wall of the maxilla. Specimens were subsequently decalcified and the bone overlying the ASAN was removed under a microscope to expose the ASAN. Its branching pattern from the infraorbital nerve was recorded, and the course of the ASAN within the anterior wall of the maxillary sinus was morphometrically assessed measuring distances to predefined landmarks using a digital caliper. A distinct ASAN was observed in all specimens. It arose lateral (six cases) or inferior (four cases) from the infraorbital nerve. The point of origin was located at a mean distance of 12.2 ± 5.79 mm posterior to the infraorbital foramen. The ASAN was located on average 2.8 ± 5.13 mm lateral to the infraorbital foramen. After coursing medially, the ASAN ran inferior to the foramen at a mean distance of 5.5 ± 3.07 mm. When approaching the nasal aperture, the loop of the ASAN was on average 13.6 ± 3.07 mm above the nasal floor. The horizontal mean distance from the ASAN to the nasal aperture was 4.3 ± 2.74 mm halfway down from the loop, and 3.3 ± 2.60 mm at the floor of the nose, respectively. In conclusion, the present study evaluated the course of the ASAN relative to the infraorbital foramen and nasal aperture. This information is helpful to avoid damage to this anatomical structure during interventions in the infraobrital region of the maxilla. Further, knowledge of the course of the ASAN and of its bony correlate (canalis sinuosus) may be valuable in interpreting anesthetic or radiologic findings in the anterior maxilla.