The dermomyotome ventrolateral lip is essential for the hypaxial myotome formation

Background The myotome is the primitive skeletal muscle that forms within the embryonic metameric body wall. It can be subdivided into an epaxial and hypaxial domain. It has been shown that the formation of the epaxial myotome requires the dorsomedial lip of the dermomyotome (DML). Although the ventrolateral lip (VLL) of the dermomyotome is believed to be required for the formation of the hypaxial myotome, experimentally evidence for this statement still needs to be provided. Provision of such data would enable the resolution of a debate regarding the formation of the hypaxial dermomyotome. Two mechanisms have been proposed for this tissue. The first proposes that the intermediate dermomyotome undergoes cellular expansion thereby pushing the ventral lateral lip in a lateral direction (translocation). In contrast, the alternative view holds that the ventral lateral lip grows laterally. Results Using time lapse confocal microscopy, we observed that the GFP-labelled ventrolateral lip (VLL) of the dermomyotome grows rather than translocates in a lateral direction. The necessity of the VLL for lateral extension of the myotome was addressed by ablation studies. We found that the hypaxial myotome did not form after VLL ablation. In contrast, the removal of an intermediate portion of the dermomyotome had very little effect of the hypaxial myotome. These results demonstrate that the VLL is required for the formation of the hypaxial myotome. Conclusion Our study demonstrates that the dermomyotome ventrolateral lip is essential for the hypaxial myotome formation and supports the lip extension model. Therefore, despite being under independent signalling controls, both the dorsomedial and ventrolateral lip fulfil the same function, i.e. they extend into adjacent regions permitting the growth of the myotome

HSP27 induced glaucomatous damage in mice of young and advanced age

IntroductionAge-related diseases such as glaucoma, a leading cause of blindness, are having an upward trend due to an aging society. In glaucoma, some patients display altered antibody profiles and increased antibody titers, for example against heat shock protein 27 (HSP27). An intravitreal injection of HSP27 leads to glaucoma-like damage in rats. We now aimed to investigate if aged mice are more prone to this damage than younger ones.MethodsWe intravitreally injected HSP27 into young (1–2 months) and aged (7–8 months) mice to compare glaucomatous damage. Respective age-matched controls received PBS. Not injected eyes served as naive controls.ResultsOptical coherence tomography 4 weeks after injection showed no changes in retinal thickness in all groups at both ages. Cell counts and RT-qPCR revealed a significant reduction in RGC numbers in HSP27 mice at both ages. Comparing aged and young HSP27 mice, no differences in Rbpms and Pou4f1 (RGCs) expression was detected, while the Tubb3 expression (neuronal cells) was significantly upregulated in aged HSP27 animals. Neither microglia/macrophages nor (resident) microglia counts revealed significant differences in HSP27 mice at both ages. Nevertheless, increased relative Iba1 and Tmem119 expression was detected in young and aged HSP27 mice. Aged HSP27 mice displayed a significantly lower Iba1 expression than young ones, whereas Cd68 levels were upregulated. A larger GFAP+ area and an upregulation of GFAP expression in HSP27 animals of both ages indicated a macrogliosis. Also, elevated Il1b and Nos2 expression levels were observed in young and aged HSP27 mice. However, only Il1b levels were upregulated when comparing 7–8 months to 1–2 months old animals. A larger HSP25+ area was seen in aged HSP27 animals, while Hspb2 expression levels were downregulated in both HSP27 groups. The aged HSP27 group displayed an upregulated Hspb2 expression compared to young mice. Furthermore, a higher optic nerve degeneration score was noted in young and aged HSP27 groups.DiscussionThese findings indicate that an intravitreal injection of HSP27 led to RGC loss accompanied by inflammation. Age-dependent effects (7–8 months vs. 1–2 months) were not very prominent. The results suggest a potential role of extracellular HSP27 in the development of glaucoma

Eddy length scales in the North Atlantic Ocean

Eddy length scales are calculated from satellite altimeter products and in an eddy-resolving model of the North Atlantic Ocean. Four different measures for eddy length scales are derived from kinetic energy densities in wave number space and spatial decorrelation scales. Observational estimates and model simulation agree well in all these measures near the surface. As found in previous studies, all length scales are, in general, decreasing with latitude. They are isotropic and proportional to the local first baroclinic Rossby radius (L r) north of about 30°N, while south of 30°N (or for L r > 30 km), zonal length scales tend to be larger than meridional ones, and (scalar) length scales show no clear relation to L r anymore. Instead, they appear to be related to the local Rhines scale. In agreement with a recent theoretical prediction by Theiss [2004], the observed and simulated pattern of eddy length scales appears to be indicative of two different dynamical regimes in the North Atlantic: anisotropic turbulence in the subtropics and isotropic turbulence in the subpolar North Atlantic. Both regions can be roughly characterized by the ration between L r and the Rhines scales (L R), with L R > L r in the isotropic region and L R < L r in the anisotropic region. The critical latitude that separates both regions, i.e., where L R = L r, is about 30°N

Intravitreal S100B Injection Leads to Progressive Glaucoma Like Damage in Retina and Optic Nerve

The glial protein S100B, which belongs to a calcium binding protein family, is up-regulated in neurological diseases, like multiple sclerosis or glaucoma. In previous studies, S100B immunization led to retinal ganglion cell (RGC) loss in an experimental autoimmune glaucoma (EAG) model. Now, the direct degenerative impact of S100B on the retina and optic nerve was evaluated. Therefore, 2 μl of S100B was intravitreally injected in two concentrations (0.2 and 0.5 μg/μl). At day 3, 14 and 21, retinal neurons, such as RGCs, amacrine and bipolar cells, as well as apoptotic mechanisms were analyzed. Furthermore, neurofilaments, myelin fibers and axons of optic nerves were evaluated. In addition, retinal function and immunoglobulin G (IgG) level in the serum were measured. At day 3, RGCs were unaffected in the S100B groups, when compared to the PBS group. Later, at days 14 and 21, the RGC number as well as the β-III tubulin protein level was reduced in the S100B groups. Only at day 14, active apoptotic mechanisms were noted. The number of amacrine cells was first affected at day 21, while the bipolar cell amount remained comparable to the PBS group. Also, the optic nerve neurofilament structure was damaged from day 3 on. At day 14, numerous swollen axons were observed. The intraocular injection of S100B is a new model for a glaucoma like degeneration. Although the application site was the eye, the optic nerve degenerated first, already at day 3. From day 14 on, retinal damage and loss of function was noted. The RGCs in the middle part of the retina were first affected. At day 21, the damage expanded and RGCs had degenerated in all areas of the retina as well as amacrine cells. Furthermore, elevated IgG levels in the serum were measured at day 21, which could be a sign of a late and S100B independet immune response. In summary, S100B had a direct destroying impact on the axons of the optic nerve. The damage of the retinal cell bodies seems to be a consequence of this axon loss

The equine gingiva: a gross anatomical evaluation

Equine periodontal disease (ePD) usually starts with food impaction, formation of diastemata, gingival inflammation and formation of periodontal pockets. This process proceeds toward the dentoalveolar space, causing detachment of tooth supporting periodontal fibers. Although several therapeutical procedures have been proposed, ePD is often only diagnosed in advanced stages, requiring dental extraction. A similar dilemma has been observed in small animal medicine, but has been overcome by the introduction of reliable examination protocols for the early diagnosis of periodontal diseases (PD). These protocols are based on detailed anatomical descriptions of healthy gingiva, allowing for the determination of the pathognomonic signs of the onset of PD and providing a basis for grading systems and treatment plans. Consequently, proposals have also been made for periodontal examination protocols in horses. However, these protocols were widely adopted from small animal medicine assuming a similar anatomy of the equine and canine gingiva. To provide a solid anatomical basis for equine specific periodontal examinations, 20 equine heads were examined macroscopically, with special attention to the gingival sulcus, the gingival margin and the interdental papillae. Constant morphological patterns of the gingival margin and the interdental papillae were found for the vestibular and lingual/palatal aspects of the upper and lower cheek teeth arcades, as well as for the incisor arcades. A gingival sulcus measuring greater than 1 mm was present in only 6% of the investigated specimens. The inspection of the gingival margin and the interdental papillae, as well as the recognition of a gingival sulcus, may serve as criteria to establish equine specific periodontal investigation protocols

A diagnosis of isopycnal mixing by mesoscale eddies

Combining the buoyancy and tracer budget in the generalised Temporal Residual Mean (TRM-G) framework of [Eden, C., Greatbatch, R.J., Olbers, D. 2007a. Interpreting eddy fluxes. J. Phys. Oceanogr. 37, 1282–1296], we show that within the small slope approximation and weakly diabatic situation, the isopycnal diffusivity is related to the difference of the streamfunctions of the eddy-induced velocities of tracer and buoyancy divided by the angle between the (negative) slopes of isopycnals and the isolines of the tracer. Using this result tracer simulations of a realistic mesoscale-eddy-permitting model of the North Atlantic coupled to a biogeochemical model are diagnosed in terms of zonal (View the MathML sourceKI(x)) and meridional (View the MathML sourceKI(y)) isopycnal diffusivities relevant for non-eddy-permitting ocean models. We find for tracers having different interior sources and surface forcing and therefore different lateral and vertical mean gradients, values of View the MathML sourceKI(x) and View the MathML sourceKI(y) with similar magnitudes and lateral and vertical structure. In general, isopycnal diffusivities lie within the expected range between 0 and 5000 m2/s but we also find a strong anisotropy with View the MathML sourceKI(x) much larger than View the MathML sourceKI(y) over large regions of the North Atlantic. Both View the MathML sourceKI(x) and View the MathML sourceKI(y) are larger within and above the thermocline but decay almost to zero below. Our results also support the common practise of the use of identical isopycnal and thickness diffusivity for any tracer in ocean models

Identification of a Novel Signaling Pathway and Its Relevance for GluA1 Recycling

We previously showed that the serum- and glucocorticoid-inducible kinase 3 (SGK3) increases the AMPA-type glutamate receptor GluA1 protein in the plasma membrane. The activation of AMPA receptors by NMDA-type glutamate receptors eventually leads to postsynaptic neuronal plasticity. Here, we show that SGK3 mRNA is upregulated in the hippocampus of new-born wild type Wistar rats after NMDA receptor activation. We further demonstrate in the Xenopus oocyte expression system that delivery of GluA1 protein to the plasma membrane depends on the small GTPase RAB11. This RAB-dependent GluA1 trafficking requires phosphorylation and activation of phosphoinositol-3-phosphate-5-kinase (PIKfyve) and the generation of PI(3,5)P2. In line with this mechanism we could show PIKfyve mRNA expression in the hippocampus of wild type C57/BL6 mice and phosphorylation of PIKfyve by SGK3. Incubation of hippocampal slices with the PIKfyve inhibitor YM201636 revealed reduced CA1 basal synaptic activity. Furthermore, treatment of primary hippocampal neurons with YM201636 altered the GluA1 expression pattern towards reduced synaptic expression of GluA1. Our findings demonstrate for the first time an involvement of PIKfyve and PI(3,5)P2 in NMDA receptor-triggered synaptic GluA1 trafficking. This new regulatory pathway of GluA1 may contribute to synaptic plasticity and memory