Wolfram-silicone implants as effective radiation shielding for ocular brachytherapy: dosimetric features and in vivo animal study on biocompatibility.

OBJECTIVE: To evaluate wolfram as a photon and beta absorber in the management of uveal melanoma with radiotherapy, examining its potential ocular adverse effects and physiologic tolerance using an in vivo rabbit ocular model. METHODS: A method of manufacturing implants from mixtures of wolfram and silicone was developed. Their shielding effect on the radiation of sources used in ocular brachytherapy was investigated by dosimetric measurement in an eye phantom as well as numerical simulations. Different wolfram implantation techniques, such as extraocular fixation of a wolfram-silicone implant (n = 1), vitrectomy with silicone oil and intravitreal injection of a wolfram-silicone oil suspension (n = 2), and concurrent attachment of a wolfram implant onto the sclera (n = 2), were tested to investigate the long-term effects of wolfram. A vitrectomy with silicone oil without wolfram implantation was carried out in 2 rabbits (n = 2), constituting the control group. The eyes were enucleated after 3 months for histologic analysis. RESULTS: Wolfram-silicone mixtures have been dosimetrically proven to be very effective radiation absorbers for use in ocular brachytherapy. Severe complications, such as endophthalmitis, secondary glaucoma, cornea decompensation, and vessel occlusion, were not documented in the tested rabbit eyes after the application of wolfram. Histologic examination of the bulbi after enucleation showed epiretinal gliosis without further pathologic findings in all eyes after vitrectomy. CONCLUSIONS: The results of this study show that wolfram and wolfram-silicone implants constitute a promising candidate as potential radiation shielding substrates.

What Can Laboratory Animal Facility Managers Do to Improve the Welfare of Laboratory Animals and Laboratory Animal Facility Staff? A German Perspective.

Laboratory animal facility managers must ensure that animal experiments can be carried out under optimal scientific conditions, that all legal requirements are met, and that animal welfare is maximized. Animal experimentation is stressful not only for the animals involved but also for the people who maintain these animals or carry out the experiments. Many of those involved find themselves in a constant conflict between scientific necessity, care, and harm. Under the term Culture of Care, procedures have been developed to reduce the burden of animal experimentation on the animals and the staff involved. The focus here is on what laboratory animal facility managers can do to improve the welfare of laboratory animals and the people working with them. Exemplary measures are the improvement of the housing conditions of laboratory animals, the introduction of uniform handling measures, clear and transparent structures via a quality management system, implementation of a no-blame culture of error (e.g., via Critical Incident Reporting System in Laboratory Animal Science [CIRS-LAS]), and open and respectful communication with all parties involved in animal experimentation, including the public and representatives of the authorities (public webpage, open house policy). The 6 Rs must be considered at all times: replacement, reduction, refinement, respect, responsibility, and reproducibility. We are writing this article from the perspective of laboratory animal facility managers in Germany.

Establishment of the body condition score for adult female Xenopus laevis.

The assessment of animals' health and nutritional status using a Body Condition Score (BCS) has become a common and reliable tool in lab-animal science. It enables a simple, semi-objective, and non-invasive assessment (palpation of osteal prominences and subcutaneous fat tissue) in routine examination of an animal. In mammals, the BCS classification contains 5 levels: A low score describes a poor nutritional condition (BCS 1-2). A BCS of 3 to 4 is considered optimum, whereas a high score (BCS = 5) is associated with obesity. While BCS are published for most common laboratory mammals, these assessment criteria are not directly applicable to clawed frogs (Xenopus laevis) due to their intracoelomic fat body instead of subcutaneous fat tissue. Therefore, this assessment tool is still missing for Xenopus laevis. The present study aimed to establish a species-specific BCS for clawed frogs in terms of housing refinement in lab-animal facilities. Accordingly, 62 adult female Xenopus laevis were weighed and sized. Further, the body contour was defined, classified, and assigned to BCS groups. A BCS 5 was associated with a mean body weight of 193.3 g (± 27.6 g), whereas a BCS 4 ranged at 163.1 g (±16.0 g). Animals with a BCS = 3 had an average body weight of 114.7 g (±16.7 g). A BCS = 2 was determined in 3 animals (103 g, 110 g, and 111 g). One animal had a BCS = 1 (83 g), equivalent to a humane endpoint. In conclusion, individual examination using the presented visual BCS provides a quick and easy assessment of the nutritional status and overall health of adult female Xenopus laevis. Due to their ectothermic nature and the associated special metabolic situation, it can be assumed that a BCS ≥3 is to be preferred for female Xenopus laevis. In addition, BCS assessment may indicate underlying subclinical health problems that require further diagnostic investigation.

Increased UHMWPE Particle-Induced Osteolysis in Fetuin-A-Deficient Mice.

Particle-induced osteolysis is a major cause of aseptic prosthetic loosening. Implant wear particles stimulate tissue macrophages inducing an aseptic inflammatory reaction, which ultimately results in bone loss. Fetuin-A is a key regulator of calcified matrix metabolism and an acute phase protein. We studied the influence of fetuin-A on particle-induced osteolysis in an established mouse model using fetuin-A-deficient mice. Ten fetuin-A-deficient (Ahsg−/−) mice and ten wild-type animals (Ahsg+/+) were assigned to test group receiving ultra-high molecular weight polyethylene (UHMWPE) particle implantation or to control group (sham surgery). After 14 days, bone metabolism parameters RANKL, osteoprotegerin (OPG), osteocalcin (OC), alkaline phosphatase (ALP), calcium, phosphate, and desoxypyridinoline (DPD) were examined. Bone volume was determined by microcomputed tomography (µCT); osteolytic regions and osteoclasts were histomorphometrically analyzed. After particle treatment, bone resorption was significantly increased in Ahsg−/− mice compared with corresponding Ahsg+/+ wild-type mice (p = 0.007). Eroded surface areas in Ahsg−/− mice were significantly increased (p = 0.002) compared with Ahsg+/+ mice, as well as the number of osteoclasts compared with control (p = 0.039). Fetuin-A deficiency revealed increased OPG (p = 0.002), and decreased levels of DPD (p = 0.038), OC (p = 0.036), ALP (p < 0.001), and Ca (p = 0.001) compared with wild-type animals. Under osteolytic conditions in Ahsg−/− mice, OPG was increased (p = 0.013), ALP (p = 0.015) and DPD (p = 0.012) were decreased compared with the Ahsg+/+ group. Osteolytic conditions lead to greater bone loss in fetuin-A-deficient mice compared with wild-type mice. Reduced fetuin-A serum levels may be a risk factor for particle-induced osteolysis while the protective effect of fetuin-A might be a future pathway for prophylaxis and treatment.

cAMP and the Fibrous Sheath Protein CABYR (Ca2+-Binding Tyrosine-Phosphorylation-Regulated Protein) Is Required for 4D Sperm Movement.

A new life starts with successful fertilization whereby one sperm from a pool of millions fertilizes the oocyte. Sperm motility is one key factor for this selection process, which depends on a coordinated flagellar movement. The flagellar beat cycle is regulated by Ca2+ entry via CatSper, cAMP, Mg2+, ADP and ATP. This study characterizes the effects of these parameters for 4D sperm motility, especially for flagellar movement and the conserved clockwise (CW) path chirality of murine sperm. Therefore, we use detergent-extracted mouse sperm and digital holographic microscopy (DHM) to show that a balanced ratio of ATP to Mg2+ in addition with 18 µM cAMP and 1 mM ADP is necessary for controlled flagellar movement, induction of rolling along the long axis and CW path chirality. Rolling along the sperm's long axis, a proposed mechanism for sperm selection, is absent in sea urchin sperm, lacking flagellar fibrous sheath (FS) and outer-dense fibers (ODFs). In sperm lacking CABYR, a Ca2+-binding tyrosine-phosphorylation regulated protein located in the FS, the swim path chirality is preserved. We conclude that specific concentrations of ATP, ADP, cAMP and Mg2+ as well as a functional CABYR play an important role for sperm motility especially for path chirality.

The antennal scape organ of Scutigera coleoptrata (Myriapoda) and a new type of arthropod tip-pore sensilla integrating scolopidial components.

BACKGROUND: Centipedes are terrestrial, predatory arthropods with specialized sensory organs. However, many aspects of their sensory biology are still unknown. This also concerns hygroreception, which is especially important for centipedes, as their epicuticle is thin and they lose water rapidly at low humidity. Thus, the detection of humid places is vital but to date no definite hygroreceptor was found in centipedes. House centipedes (Scutigeromorpha) possess a peculiar opening at the base of their antenna, termed 'scape organ', that houses up to 15 cone-shaped sensilla in a cavity. Lacking wall and tip-pores, these socket-less sensilla may be hypothesized to function as hygroreceptors similar to those found in hexapods. RESULTS: The cone-shaped sensilla in the scape organ as well as nearby peg-shaped sensilla are composed of three biciliated receptor cells and three sheath cells. A tip-pore is present but plugged by a highly electron-dense secretion, which also overlays the entire inner surface of the cavity. Several solitary recto-canal epidermal glands produce the secretion. Receptor cell type 1 (two cells in cone-shaped sensilla, one cell in peg-shaped sensilla) possesses two long dendritic outer segments that project to the terminal pore. Receptor cell type 2 (one cell in both sensilla) possesses two shorter dendritic outer segments connected to the first (proximal) sheath cell that establishes a scolopale-like structure, documented for the first time in detail in a myriapod sensillum. CONCLUSIONS: The nearly identical configuration of receptor cells 1 with their long dendritic outer segments in both sensilla is similar to hexapod hygroreceptors. In Scutigera coleoptrata, however, the mechanism of stimulus transduction is different. Water vapor may lead to swelling and subsequent elongation of the plug pin that enters the terminal pore, thus causing stimulation of the elongated dendritic outer segments. The interconnection of receptor cell 2 with short outer dendritic segments to a scolopale-like structure potentially suits both sensilla for vibration or strain detection. Thus, both sensilla located at the antennal base of scutigeromorph centipedes fulfill a dual function.

Prednisone prevents particle induced bone loss in the calvaria mouse model.

INTRODUCTION: Glucocorticoids are essential in the treatment of many chronic inflammatory and malignant diseases but are known to have detrimental effects on bone. This study aimed to investigate the effects of prednisone on osteoclast functioning in vivo in the calvaria particle-induced bone loss mouse model. METHODS: 12-week-old male C57BL6/J mice received subcutaneously implanted prednisone (2.5 mg/d, 60 day release (n = 14)) or placebo pellets (n = 10). Osteolysis of the calvaria bone was induced two weeks later by application of ultra-high-molecular-weight polyethylene- (UHMWPE) particles to the dome (vs sham operation). The extent of osteolysis was determined histologically and by micro-computer tomography. RESULTS: Prednisone significantly inhibited particle-induced osteolysis in the skull. No significant difference in osteoclast numbers was seen in mice with prednisone vs placebo treatment. Prednisone treatment alone without particle application did not reduce bone mineral density or deterioration in bone microarchitecture parameters. CONCLUSIONS: The calvaria particle-induced bone loss mouse model can be adapted to investigate osteoclast activity in vivo and the effect of prednisone on osteoclasts. In this preventive experimental design, the application of short-term low-dose prednisone has osteoprotective effects without measurable systemic side effects on bone parameters.

In-vivo comparison of the Ni-free steel X13CrMnMoN18-14-3 and titanium alloy implants in rabbit femora - A promising steel for orthopedic surgery.

A variety of metallic biomaterials is used for fracture fixation. Allergic reactions towards nickel-containing steels urge the need for alternatives. The present study investigated the suitability of the nickel-free stainless steel P2000 in comparison to titanium alloy implants for bone surgical applications in a rabbit femora defect model. Thirty-six rabbits received two different cylindrical implants press-fit inserted into the distal femoral metaphysis. At day 0, 28, and 56, implant ingrowth was monitored by radiography; implant stability was assessed by pull-out torque measurements while bone-to-implant contact (BIC) was determined histomorphometrically. Radiography revealed comparable implant ingrowth after 1 and 2 months for both implant materials. The pull-out force of P2000 tended to be higher than that for titanium at day 28 (p = .076) but the values were comparable at day 56 (p = .905). At day 56, implant fixation was significantly increased compared to the day of surgery for both, P2000 (p = .030) and for titanium alloy (p = .026). Microscopic examination revealed that both implant types appeared to be well integrated and firmly anchored in the bone. BIC ratio of titanium alloy tended to be higher at day 28 (p = .079) but they did not differ significantly at day 56 (p = .711). In the present rabbit femora defect model, the nickel-free stainless steel P2000 provides primary stability and osseointegration comparable to that of titanium alloy implants.

The tracheal system of scutigeromorph centipedes and the evolution of respiratory systems of myriapods.

The tracheal system of scutigeromorph centipedes (Chilopoda) is special, as it consists of dorsally arranged unpaired spiracles. In this study, we investigate the tracheal systems of five different scutigeromorph species. They are strikingly similar to each other but depict unique characters compared to the tracheal systems of pleurostigmophoran centipedes, which has engendered an ongoing debate over a single versus independent origin of tracheal systems in Chilopoda. Up to now, only the respiratory system of Scutigera coleoptrata was investigated intensively using LM-, TEM-, and SEM-techniques. We supplement this with data for species from all three families of Scutigeromorpha. These reveal interspecific differences in atrial width and the shape and branching pattern of the tracheal tubules. Further, we investigated the tracheal system of Scutigera coleoptrata with three additional techniques: light sheet microscopy, microCT and synchrotron radiation based microCT analysis. This set of techniques allows a comparison between fresh versus fixed and dried material. The question of a unique vs. multiple origin of tracheal systems in centipedes and in Myriapoda as a whole is discussed with regard to their structural similarities and differences and the presence of hemocyanin as an oxygen carrier. We used morphological and molecular data and the fossil record to evaluate the alternative hypotheses.

Porcine slaughterhouse lungs for ex vivo lung perfusion - a pilot project.

Ex vivo lung perfusion (EVLP) is an emerging technique for evaluation and eventual reconditioning of donor lungs. Before clinical use experiments with laboratory animals are standard. It was the aim of this study to compare lungs evaluated with EVLP from laboratory animals with slaughterhouse lungs and to investigate the potential use of a slaughterhouse lung model for ex vivo lung perfusion as an alternative for the use of laboratory animals. In a porcine model of Donation after Circulatory Determination of Death (DCDD) 16 lungs were obtained either from regular slaughterhouse animals (SL n = 8) or from laboratory animals in organ procurements (SS n = 8). Lungs were flushed and stored cold for four hours in Perfadex Plus™ and subsequently perfused ex vivo with Steen Solution™ for up to four hours. During 4 hours of EVLP lung functional parameters and activities of lactate, lactate dehydrogenase (LDH) and alkaline phosphatase (AP) in the perfusate were recorded hourly. Histological samples were taken and evaluated fur Lung Injury. Lungs showed no significant difference in oxygen capacity in between groups (∆ PO2 averaged over 4 hours: SL 293 ± 187 mmHg SS 247 ± 199 mmHg). LDH concentration was significantly higher in slaughterhouse lungs (SL 438,5 ± 139,8 U/l, SS 258,42 ± 108,4 U/l P ≤ 0,01). We conclude that the use of slaughterhouse lungs for EVLP was feasible with no significant disadvantages compared to standard organ procurement lungs regarding lung functional outcomes. With the use of slaughterhouse lungs animal experiments in EVLP research could be successfully reduced.

Clinical Development of Sphingosine as Anti-Bacterial Drug: Inhalation of Sphingosine in Mini Pigs has no Adverse Side Effects.

BACKGROUND/AIMS: Pulmonary infections with Pseudomonas aeruginosa (P. aeruginosa) or Staphylococcus aureus (S. aureus) are of utmost clinical relevance in patients with cystic fibrosis, chronic obstructive pulmonary disease, after trauma and burn, upon ventilation or in immuno-compromised patients. Many P. aeruginosa and S. aureus strains are resistant to many known antibiotics and it is very difficult or often impossible to eradicate the pathogens in patient´s lungs. We have recently shown that the sphingoid base sphingosine very efficiently kills many pathogens, including for instance P. aeruginosa, S. aureus or Acinetobacter baumannii, in vitro. In vivo experiments of our group on cystic fibrosis mice indicated that inhalation of sphingosine prevents or eliminates existing acute or chronic pneumonia with P. aeruginosa or S. aureus in these mice. We also demonstrated that sphingosine is safe to use for inhalation up to high doses, at least in mice. To facilitate development of sphingosine to an anti-bactericidal drug that can be used in humans for inhalation, safety data on non-rodents, larger animals are absolutely required. METHODS: Here, we inhaled mini pigs with increasing doses of sphingosine for 10 days and analyzed the uptake of sphingosine into epithelial cells of bronchi as well as into the trachea and lung and the systemic circulation. Moreover, we measured the generation of ceramide and sphingosine 1-phosphate that potentially mediate inflammation, the influx of leukocytes, epithelial cell death and disruption of the epithelial cell barrier. RESULTS: We demonstrate that inhalation of sphingosine results in increased levels of sphingosine in the luminal membrane of bronchi and the trachea, but not in systemic accumulation. Inhaled sphingosine had no side effects up to very high doses. CONCLUSION: In summary, we demonstrate that inhalation of sphingosine results in an increase of sphingosine concentrations in the luminal plasma membrane of tracheal and bronchial epithelial cells. The inhalation has no systemic or local side effects.

A single intraperitoneal injection of bovine fetuin-A attenuates bone resorption in a murine calvarial model of particle-induced osteolysis.

Particle-induced osteolysis, which by definition is an aseptic inflammatory reaction to implant-derived wear debris eventually leading to local bone destruction, remains the major reason for long-term failure of orthopedic endoprostheses. Fetuin-A, a 66kDa glycoprotein with diverse functions, is found to be enriched in bone. Besides being an important inhibitor of ectopic calcification, it has been described to influence the production of mediators of inflammation. Furthermore, a regulatory role in bone metabolism has been assigned. In the present study, the influence of a single dose of bovine fetuin-A, intraperitoneally injected in mice subjected to particle-induced osteolysis of the calvaria, was analyzed. Twenty-eight male C57BL/6 mice, twelve weeks of age, were randomly divided into four groups. Groups 2 and 4 were subjected to ultra-high molecular weight polyethylene (UHMWPE) particles placed on their calvariae while groups 1 and 3 were sham-operated. Furthermore, groups 3 and 4 received a single intraperitoneal injection of 20mg bovine fetuin-A while groups 1 and 2 were treated with physiologic saline. After 14days calvarial bone was qualitatively and quantitatively assessed using microcomputed tomography (µCT) and histomorphometrical approaches. Application of fetuin-A led to a reduction of particle-induced osteolysis in terms of visible osteolytic lesions and eroded bone surface. The reduction of bone thickness and bone volume, as elicited by UHMWPE, was alleviated by fetuin-A. In conclusion, fetuin-A was found to exert an anti-resorptive effect on particle-induced osteolysis in-vivo. Thus, fetuin-A could play a potentially osteoprotective role in the treatment of bone metabolic disorders.

Interaction of the tracheal tubules of Scutigeracoleoptrata (Chilopoda, Notostigmophora) with glandular structures of the pericardial septum.

Notostigmophora (Scutigeromorpha) exhibit a special tracheal system compared to other Chilopoda. The unpaired spiracles are localized medially on the long tergites and open into a wide atrium from which hundreds of tracheal tubules originate and extend into the pericardial sinus. Previous investigators reported that the tracheal tubules float freely in the hemolymph. However, here we show for the first time that the tracheal tubules are anchored to a part of the pericardial septum. Another novel finding is this part of the pericardial septum is structured as an aggregated gland on the basis of its specialized epithelium being formed by hundreds of oligocellular glands. It remains unclear whether the pericardial septum has a differently structure in areas that lack a connection with tracheal tubules. The tracheal tubules come into direct contact with the canal cells of the glands that presumably secrete mucous substances covering the entire luminal cuticle of the tracheal tubules. Connections between tracheae and glands have not been observed in any other arthropods.

The role of calcitonin receptor signalling in polyethylene particle-induced osteolysis.

The detection of peptides from the calcitonin (CT) family in the periarticular tissue of loosened implants has raised hopes of opening new regenerative therapies in the process of aseptic loosening, which remains the major cause of early implant failure in endoprosthetic surgery. We have previously shown the roles of α-calcitonin gene-related peptide (α-CGRP) and the CALCA gene which encodes α-CGRP/CT in this process. To uncover the role of direct calcitonin receptor (CTR) mediated signalling, we studied particle-induced osteolysis (PIO) in a murine calvaria model with a global deletion of the CTR (CTR-KO) using µCT analysis and histomorphometry. As expected, CTR-KO mice revealed reduced bone volume compared to wild-type (WT) controls (p<0.05). In CTR-KO mice we found significantly higher RANKL (receptor activator of NF-κB ligand) expression in the particle group than in the control group. The increase in osteoclast numbers by the particles was twice as high as the increase of osteoclasts in the WT mice (400 vs. 200%). Changes in the eroded surface and actual osteolysis due to ultrahigh-molecular-weight polyethylene particles were similar in WTs and CTR-KOs. Taken together, our findings strengthen the relevance of the OPG/RANK/RANKL system in the PIO process. CTR seems to have an effect on osteoclast differentiation in this context. As there were no obvious changes of the amount of PIO in CTR deficiency, regenerative strategies in aseptic loosening of endoprosthetic implants based on peptides arising from the CT family should rather focus on the impact of α-CGRP.

Adiponectin attenuates osteolysis in aseptic loosening of total hip replacements.

Joint replacements have a longer durability in patients with high serum levels of adiponectin (APN) than in patients with low levels. We aimed to characterize the unknown pathophysiological effects of APN on wear particle-induced inflammation, apoptosis and osteolysis. Immunohistochemistry was performed to detect APN, its receptors and apoptosis in patients with and without aseptic loosening. Additionally, APN knockout mouse studies and pharmacological intervention of APN were performed in an established calvarial mouse model. Osteolysis and inflammation were quantified by histomorphometry and microcomputed tomography, apoptosis by immunohistochemistry and TUNEL assay. In a cell culture model, human monocyte-derived macrophages were incubated with or without metal wear debris particles and partially treated with APN. Expression of APN, AdipoR1 and calreticulin in specimens from patients with aseptic loosening were significantly higher than in patients without aseptic loosening. Administration of APN in mice significantly reduced wear particle-induced inflammation, osteolysis and the number of caspase-3-positive macrophages. The cell culture model showed that APN leads to significantly lower values of TNF-α. These findings support a prominent role of APN in the development of particle-induced osteolysis and APN may be therapeutically useful in patients with aseptic loosening.

Ultrastructure, functional morphology and evolution of recto-canal epidermal glands in Myriapoda.

In Chilopoda, solitary epidermal glands are composed of a couple of cells only. These glands are highly abundant on the entire body surface and are distributed throughout the single-layered epidermis. Some authors provided more or less comprehensive observations on the structure of epidermal glands of specific chilopod taxa. However, no information is hitherto available on the ultrastructural diversity of these glands. Furthermore, potential homologies of these chilopod epidermal glands and of their characteristic cellular components remain unknown. Based on our results, we are now able to distinguish two types of epidermal glands in Chilopoda that can be clearly distinguished by their structure and the course of their conducting canal: recto-canal epidermal glands (rceg) and flexo-canal epidermal glands (fceg). In the present paper, we focus on the rceg. We examined the ultrastructural organization of these glands in the head region and on the anterior trunk segments of various representatives of the five extant chilopod orders by light- and electron-microscopy. According to our terminology, rceg consist of up to five different cell types including: a) distal canal cells, b) proximal canal cells, c) intermediary cells, and d) two different types of secretory cells. Intermediary and canal cells form a common conducting canal. The rceg may taxon-specifically differ in relative size and subcellular architecture, but all have the following features in common: 1) a wide distribution on various body regions among all five chilopod subtaxa, 2) the straight, broad and locally dilated conducting canal surrounded by closely packed microvilli or microvilliform infoldings around the apex of the canal cell(s), and 3) the tendency to aggregate to form compound glandular organs of massive size and complexity. Tricellular glandular units established by three different cell types are observed in Scutigeromorpha and Geophilomorpha, whereas four cell types constitute rceg in Lithobiomorpha and Craterostigmomorpha. Five different cell types per glandular unit are found only in Scolopendromorpha. The partial cuticularization of the lower part of the conducting canal formed by the intermediary cell, as found in Chilopoda, differs from the pattern described for equivalent euarthropod epidermal glands, as for instance in Hexapoda. Their wide distribution in Chilopoda and Progoneata makes it likely that tricellular rceg were at least present in the last common ancestor of the Myriapoda. Concerning Chilopoda, the evolution of highly diverse rceg is well explained on the basis of the Pleurostigmophora concept. Glands of the recto-canal type are also found in other arthropods. The paper discusses cases where homology of rceg and also fceg may be assumed beyond Myriapoda and briefly evaluates the potentials and the still-to-be-solved issues prior to use them as an additional character system to reconstruct the phylogeny of the Euarthropoda.

RANKL-associated suppression of particle-induced osteolysis in an aged model of Calcitonin and α-CGRP deficiency.

An aging population with higher bone turnover intensifies the need for joint replacement surgery. However, particle-induced osteolysis (PIO) remains a major cause of early implant loosening. Differences in bone remodeling between young and aged Calcitonin (CT)- and α-CGRP (Calcitonin gene-related peptide)-deficient mice (Calca(-/-)) might modify our previous findings regarding CT/α-CGRP in PIO. This may have important implications for PIO in an aging population. Four groups of twelve-month-old wild-type and Calca(-/-) mice underwent either SHAM surgery with and without CT, or polyethylene-particle implantation with related treatment. Morphometric changes were detected using µ-CT, histomorphometric analysis and by counting TRAP(+) cells (osteoclast-staining). Bone remodeling was assessed using serum and urinary markers. There was no osteolysis in aged particle-treated Calca(-/-) animals and the effect of CT on PIO was reduced compared to wild-type mice. However, there were significantly higher numbers of TRAP(+) cells in Calca(-/-) animals, and bone remodeling markers revealed a significant increase in OPG/OCN and a significant reduction in RANKL compared to aged wild-type mice. CT/α-CGRP modulates bone cell activity in PIO in aged mice in a way that is distinct from young animals. This may have implications for the treatment of PIO in the periprosthetic surface of joint replacements in an aging population.

The source of chilopod sensory information: external structure and distribution of antennal sensilla in Scutigera coleoptrata (chilopoda, Scutigeromorpha).

The investigation of the antennae of Scutigera coleoptrata (Linnaeus, 1758) by scanning electron microscopy (SEM) revealed the presence of five types of sensilla: sensilla trichodea, beak-like sensilla, cone-shaped sensilla brachyconica on the terminal article, sensory cones at the antennal nodes, and the shaft organ. Alongside the presence and absence of antennal sensillar types, three unique characters were found in the Scutigeromorpha: the presence of long antennae with nodes bearing sensory cones, the presence of a bipartite shaft including the shaft organ, and the presence of beak-like sensilla. Neuroanatomical data showed that the animals' brains are equipped with well-developed primary olfactory and mechanosensory centers, suggesting that the antennae must be equipped with specialized sensilla to perceive chemosensory and mechanosensory cues. With the evidence provided in this article for the Scutigeromorpha, SEM data are available at last on the antennal sensilla for all five chilopod taxa, allowing a comparative discussion of antennal morphology in Chilopoda.