Role of juvenile hormone in the synthesis and sequestration of vitellogenins in the red cotton stainer, Dysdercus koenigii (Heteroptera : Pyrrhocoridae)

Investigations were carried out to determine the role of juvenile hormone (JH) and 20-hydroxy ecdysone in the synthesis and uptake of vitellogenins, which were earlier identified, purified and characterised, in Dysdercus koenigii. The concentration(s) of vitellogenin(s) in fat body, haemolymph and that of vitellin(s) in ovary were significantly lower after chemical allatectomy at eclosion. In addition, at 70 h after emergence, chemical allatectomy reduced ovarian vitellin concentration, but vitellogenin levels remained normal in the fat body and haemolymph. The haemolymph vitellogenins were not incorporated into oocytes in such insects. Administration of JH-III at 20 h after allatectomy restored vitellogenin levels in the fat body and haemolymph, but the ovary failed to incorporate the available vitellogenins from haemolymph in such insects. However, when JH-III was administered twice, one at 20 h and then at 70 h after allatectomy, vitellogenin concentrations in fat body and haemolymph and also vitellin concentrations in ovary approached control levels. It is suggested that JH has two separate roles, one in vitellogenin synthesis and the other in uptake. 20-hydroxy ecdysone had no apparent role in either vitellogenin synthesis or uptake in D. koenigii. (C) 2000 Elsevier Science Inc. All rights reserved.

Novel multimeric IL-1 receptor antagonist for the treatment of rheumatoid arthritis

Protein therapeutics targeting inflammatory mediators have shown great promise for the treatment of autoimmunities such as rheumatoid arthritis (RA). However, a significant challenge in this area has been their low in vivo stability and consequently their severely compromised therapeutic efficacy. One such therapeutic molecule IL-1 receptor antagonist (IL-1ra), used in the treatment of rheumatoid arthritis, has displayed only modest efficacy in human clinical trials owing to its short biological half-life. Herein, we report a novel approach to conglomerate individual protein entities into a drug depot by incorporation of an amyloidogenic motif Lys-Phe-Phe-Glu (KFFE) thereby dramatically improving their systemic persistence and in turn their therapeutic efficacy in a mice model of autoimmune arthritis. (C) 2014 Elsevier Ltd. All rights reserved.

WNT-Inflammasome Signaling Mediates NOD2-Induced Development of Acute Arthritis in Mice

In addition to its role in innate immunity, the intracellular pathogen sensor nucleotide-binding oligomerization domain 2 (NOD2) has been implicated in various inflammatory disorders, including the development of acute arthritis. However, the molecular mechanisms involved in the development of NOD2-responsive acute arthritis are not clear. In this study, we demonstrate that NOD2 signals to a cellular protein, Ly6/PLAUR domain-containing protein 6, in a receptor-interacting protein kinase 2-TGF-beta-activated kinase 1-independent manner to activate the WNT signaling cascade. Gain- or loss-of-function of the WNT signaling pathway in an in vivo experimental mouse arthritis model or in vitro systems established the role for WNT-responsive X-linked inhibitor of apoptosis during the development of acute arthritis. Importantly, WNT-stimulated X-linked inhibitor of apoptosis mediates the activation of inflammasomes. The subsequent caspase-1 activation and IL-1 beta secretion together contribute to the phenotypic character of the inflammatory condition of acute arthritis. Thus, identification of a role for WNT-mediated inflammasome activation during NOD2 stimulation serves as a paradigm to understand NOD2-associated inflammatory disorders and develop novel therapeutics.

Regeneration of Juvenile Woody Plants after Fire in a Seasonally Dry Tropical Forest of Southern India

Woody tree species in seasonally dry tropical forests are known to have traits that help them to recover from recurring disturbances such as fire. Two such traits are resprouting and rapid post-fire growth. We compared survival and growth rates of regenerating small-sized individuals (juveniles) of woody tree species after dry season fire (February-March) at eight adjacent pairs of burnt and unburnt transects in a seasonally dry tropical forest in southern India. Juveniles were monitored at 3-mo intervals between August 2009 and August 2010. High juvenile survivorship (>95%) was observed in both burnt and unburnt areas. Growth rates of juveniles, analyzed at the community level as well as for a few species individually (especially fast-growing ones), were distinctly higher in burnt areas compared to unburnt areas after a fire event, particularly during the pre-monsoon season immediately after a fire. Rapid growth by juveniles soon after a fire may be due to lowered competition from other vegetative forms such as grasses, possibly aided by the availability of resources stored belowground. Such an adaptation would allow a juvenile bank to be retained in the understory of a dry forest, from where individuals can grow to a possible fire-tolerant size during favorable conditions.