Systems analysis of primary Sjögren's syndrome pathogenesis in salivary glands identifies shared pathways in human and a mouse model

Bone tissue has an exceptional quality to regenerate to native tissue in response to injury. However, the fracture repair process requires mechanical stability or a viable biological microenvironment or both to ensure successful healing to native tissue. An improved understanding of the molecular and cellular events that occur during bone repair and remodeling has led to the development of biologic agents that can augment the biological microenvironment and enhance bone repair. Orthobiologics, including stem cells, osteoinductive growth factors, osteoconductive matrices, and anabolic agents, are available clinically for accelerating fracture repair and treatment of compromised bone repair situations like delayed unions and nonunions. Preclinical and clinical studies using biologic agents like recombinant bone morphogenetic proteins have demonstrated an efficacy similar or better than that of autologous bone graft in acute fracture healing. A lack of standardized outcome measures for comparison of biologic agents in clinical fracture repair trials, frequent off-label use, and a limited understanding of the biological activity of these agents at the bone repair site have limited their efficacy in clinical applications.     

Effect of Bacillus thuringiensis Cry1 Toxins in Insect Hemolymph and Their Neurotoxicity in Brain Cells of Lymantria dispar

Little information is available on the systemic effects of Bacillus thuringiensis toxins in the hemocoel of insects. In order to test whether B. thuringiensis-activated toxins elicit a toxic response in the hemocoel, we measured the effect of intrahemocoelic injections of several Cry1 toxins on the food intake, growth, and survival of Lymantria dispar (Lepidoptera) and Neobellieria bullata (Diptera) larvae. Injection of Cry1C was highly toxic to the Lymantria larvae and resulted in the complete inhibition of food intake, growth arrest, and death in a dose-dependent manner. Cry1Aa and Cry1Ab (5 μg/0.2 g [fresh weight] [g fresh wt]) also affected growth and food intake but were less toxic than Cry1C (0.5 μg/0.2 g fresh wt). Cry1E and Cry1Ac (5 μg/0.2 g fresh wt) had no toxic effect upon injection. Cry1C was also highly toxic to N. bullata larvae upon injection. Injection of 5 μg/0.2 g fresh wt resulted in rapid paralysis, followed by hemocytic melanization and death. Lower concentrations delayed pupariation or gave rise to malformation of the puparium. Finally, Cry1C was toxic to brain cells of Lymantria in vitro. The addition of Cry1C (20 μg/ml) to primary cultures of Lymantria brain cells resulted in rapid lysis of the cultured neurons.     

Behavioural differences in Locusta migratoria associated with albinism and their relation to [His7]-corazonin

Abstract. The neuropeptide [His⁷]-corazonin induces black colouration in locusts, a feature typically occurring in gregarious animals. To date, the function of this neuropeptide in relation to phase transition has not been fully clarified. Unanswered questions on its involvement in behavioural and morphometrical phaseshifting and possible temperature-induced regulation still remain. In the African locust, Locusta migratoria migratorioides (Reiche and Fairmaire) (Orthoptera: Acrididae), the gregarious form possesses mainly a brown colouration with typical intense black pigmentation. To find a possible behavioural function, an albino L. migratoria mutant, deficient in [His⁷]-corazonin and thus lacking the typical gregarious colour, was used. Between these two phenotypes, nonphase specific behavioural differences in a phase-dependent behavioural set-up were found. Additionally, a wild-type of the Okinawa strain was screened behaviourally and located in comparison to the other groups. Treatment of albinos with corazonin induced normal phenotype behaviour. The degree of interference of corazonin in relation to these findings and a possible effect at the level of visual perception is discussed.     

The endocrine control of phase transition: some new aspects

Abstract. The present article summarizes some recent findings relating to the underlying mechanism of phase transition in locusts, from the nonswarming solitarious phase to the swarming gregarious phase. These phases differ in many traits, such as colouration, morphometrics and behaviour. The most comprehensive theory at present to explain the switch from the nonswarming to the swarming form is that the locusts are brought together by the heterogeneity of the environment. They gather at preferential structures and food plants and physical contact then stimulates individuals to gregarize. Phase change can also be transferred across generations by maternal pheromones. The endocrine regulation of phase polymorphism is still not fully understood. The role of ecdysteroids has been studied, so far with no final conclusion. It is remarkable that the prothoracic glands persist longer in isolated-reared adults, which implies that these glands continue to play a role, although they no longer release important amounts of ecdysteroids. Juvenile Hormone, without any doubt, induces certain solitarious characteristics, such as green colouration, but is not the primary causal factor. A real breakthrough was the discovery of [His⁷]-corazonin, made possible by using a novel assay system, the Okinawa albino mutant of Locusta migratoria , which was known to be deficient in this hormone. This peptide, which is produced in the brain and is most likely released via the corpora cardiaca, promotes the gregarious black pigmentation. It also plays a role in morphometrical phase change as well as in behavioural alterations. Corazonin is apparently quite an important peptide not only in locusts, but also in insects in general.     

Purification, isolation and search for possible functions of a phase-related 6080-Da peptide from the haemolymph of the desert locust, Schistocerca gregaria

Abstract. A novel 6-kDa peptide has been isolated from the haemolymph of the desert locust, Schistocerca gregaria (Forskal) (Orthoptera: Acrididae) , and fully identified. Its concentration is higher in crowd-reared (gregarious) animals than in isolated-reared (solitarious) ones. Its concentration decreases progressively from generation to generation with solitarization of gregarious locusts. The peptide is also present in freshly laid eggs. The concentration in eggs is higher in those from crowd-reared locusts. It is likely that the peptide is transferred from the female's haemolymph into the eggs because injection of the peptide into females before oviposition increases the amount of the 6-kDa peptide in the eggs. A two-step HPLC purification procedure for this peptide is described. It allowed several bioassays to test for a possible function. Although the peptide's concentration in the haemolymph is high (0.1 m m ), which suggests some physiological function, we have as yet not been able to identify a function. We hypothesize that the 6-kDa peptide may somehow play a role as a maternal factor in the determination of the phase-state of the offspring.     

Localization of CRF immunoreactivity in the central nervous system of three vertebrate and one insect species

Summary By use of a specific antiserum against synthetic ovine corticotropin-releasing factor (CRF) in the peroxidase-antiperoxidase (PAP) immunocytochemical procedure (Vandesande and Dierickx 1976), CRF-like antigenic determinants were demonstrated in the central nervous system of a human fetus, the Wistar rat, the frog Rana ridibunda, and the American cockroach Periplaneta americana. The immunoreactive CRF-producing cells occur mainly in the nucleus paraventricularis of the rat, while in Rana ridibunda these cells occur in the nucleus praeopticus. Immunoreactive CRF-containing fibres were also visualized. Very clear CRF-immunoreactive products were observed in the brain as well as the corpora cardiaca (CC) and corpora allata (CA) of the cockroach Periplaneta americana. ACTH-immunoreactivity was also demonstrated in the brain-CC-CA complex of this insect. Double immunohistochemical staining (Vandesande 1983) also revealed that both the CRFand ACTH-like substances occur in different neurosecretory neurons and nerve fibres. These results suggest that the antigenic determinants of CRF are very similar in vertebrates and insects bespeaking their very long evolutionary history.     

Substance P-like immunoreactivity in the central nervous system of the blattarian insect Periplaneta americana L. revealed by a monoclonal antibody

Summary Brains, retrocerebral complexes and frontal and suboesophageal ganglia of adult American cockroaches, Periplameta americana, were immunohistochemically investigated with a specific monoclonal antibody (McAb) directed against a well characterized antigenic determinant, namely the COOH terminus of the endecapeptide substance P (SP). This resulted in the detection of several neurons and nerve fibres containing a substance antigenically closely related to this typically vertebrate neuropeptide.No difference in staining pattern could be observed between male and female insects. Related to the age of the adult specimens, however, a slight quantitative difference in SP immunoreactivity seems to occur, which probably might have functional implications. The SP-like peptide demonstrated in this study appears to be located in different neuronal structures than the ones that we earlier described as containing ACTH-, CRF-, OT-, AVP-, NP I-, NP II-, BPP-, FMRFamide-, AKH-, met-ENK-, FSH-, LH- and LHRF-like material (Verhaert et al. 1984a, b, 1985; Verhaert and De Loof 1985a, b).     

All animals develop from a blastula: consequences of an undervalued definition for thinking on development.

An early embryo becomes a blastula at the moment that its constituent cells become organised into a simple epithelium. Epithelial folding and compartmentation are essential elements of animal development. All the different cell types--epithelial and other ones--of which a differentiated organism consists differ in their plasmamembrane-cytoskeletal complex but they are assumed to have an identical genome. The hypothesis is put forward that, perhaps, the basic mechanism underlying differentiation can be defined as the generation of cells which have an identical genome but which differ in their plasmamembrane-cytoskeletal complex and which, because of these differences, can engage in differential protein synthesis-physiology.     

Diapause phenomena in non-diapausing last instar larvae,pupae, and pharate adults of the Colorado beetle

From the first day of the last (fourth) larval instar no trace of juvenile hormone (JH) can be detected in the haemolymph by Galleria bioassay. Three specific diapause proteins, which are also found in diapausing adults, appear in the haemolymph. These proteins disappear towards the end of the pupal stage. Study of the ultrastructure of the fat body revealed the formation from lysosomes of proteinaceous bodies which are also characteristic for adult diapause. The behaviour of last instar larvae and pupae resembles that of prediapausing and diapausing adults respectively. Injection of synthetic JH delays the appearance of the diapause proteins in the haemolymph and of proteinaceous bodies in the fat body for 2 to 3 days. The absence of JH seems to trigger off these diapause phenomena.