Laboratory and field assessment of molluscicidal activity of B-2 against Oncomelania hupensis, the vector snail of schistosomiasis in China

Molluscicidal activity of B-2 (sodium 2,5-dichloro-4-bromophenol; called as Phebrol and registered in WHO as OMS 3012) was evaluated in a laboratory and the field trials were performed in two different localities in Yueyang city, China, for control of Oncomelania hupensis. B-2 was effective against O. hupensis both in the laboratory and in the field. A dosage of 50 g/m2 in 10% granular form or 20 ml/m2 in 25% liquid form of B-2 would be recommendable as a standard mollusciciding dose for control of O. hupensis.     

Botanische Notizen aus Griechenland

Ohne Zusammenfassung     

Histidine Residue Mediates Radical-induced Hinge Cleavage of Human IgG1

Hydroxyl radicals induce hinge cleavage in a human IgG1 molecule via initial radical formation at the first hinge Cys²³¹ followed by electron transfer to the upper hinge residues. To enable engineering of a stable monoclonal antibody hinge, we investigated the role of the hinge His²²⁹ residue using structure modeling and site-directed mutagenesis. Direct involvement of His²²⁹ in the reaction mechanism is suggested by a 75–85% reduction of the hinge cleavage for variants in which His²²⁹ was substituted with either Gln, Ser, or Ala. In contrast, mutation of Lys²²⁷ to Gln, Ser, or Ala increased hinge cleavage. However, the H229S/K227S double mutant shows hinge cleavage levels similar to that of the single H229S variant, further revealing the importance of His²²⁹. Examination of the hinge structure shows that His²²⁹ is capable of forming hydrogen bonds with surrounding residues. These observations led us to hypothesize that the imidazole ring of His²²⁹ may function to facilitate the cleavage by forming a transient radical center that is capable of extracting a proton from neighboring residues. The work presented here suggests the feasibility of engineering a new generation of monoclonal antibodies capable of resisting hinge cleavage to improve product stability and efficacy.     

Unrestrained production of proopiomelanocortin (POMC) and its peptide fragments by pituitary corticotroph adenomas in Cushing's disease.

The hallmark of ACTH oversecretion in Cushing's disease is its partial resistance to the normal suppressive effect of glucocorticoids. Because ACTH secretion by the pituitary tumor is not normally restrained ACTH is overproduced with subsequent chronic hypercortisolism. Since peripheral tissues have retained their normal sensitivity to the action of cortisol they appropriately develop the features of Cushing's disease. The question of whether a collection of corticotroph cells, eventually arranged in an adenomatous-like fashion, is a primary pituitary event or is corticotropin-releasing factor driven has had no response so far. Clonal composition of such lesions has been determined by X chromosome inactivation using DNA probes which detect multiallelic polymorphism in females. A monoclonal pattern is found in all macroadenomas. ACTH is co-secreted with other peptide fragments derived from their common polypeptide precursor, proopiomelanocortin (POMC). As a rule POMC processing in pituitary tumors is qualitatively unaltered: plasma values of the N-terminal fragment, the joining peptide, the beta- and gamma-lipotropins, and beta-endorphin all are valid alternate markers of the tumor activity. Tumor POMC peptides including ACTH and its phosphorylated form usually show no peculiar or unexpected molecular forms in contrast with what is often found when POMC expression occurs in a non-pituitary tumor.     

The ω-endotoxin protein family displays a hydrophobic motif that might be implicated in toxicity

A computer-based analysis of hydropathy and surface probability of representative members of each class of the Cry family of proteins was performed. A highly conserved hydrophobic motif within the previously described block, D2, is present not only in lepidopteran toxin genes but also in toxins active against diptera and coleoptera. An interesting feature of this hydrophobic motif is the presence of an aspartic residue (highly hydrophilic) in its middle part. Comparison with the amino acid sequence from diphtheria toxin showed that it also contains a hydrophobic motif similar to the one present in the Bacillus thuringiensis toxins. It also contains an aspartic residue in the middle part and some speculations are presented on the function of this specific region with regard to the toxic mechanism of action.     

Expression patterns and association analysis of the porcine DHX58 gene

RIG-1 signalling is responsible for the detection of cytoplasmic viral RNA molecules. DEXH (Asp-Glu-X-His) box polypeptide 58 (encoded by DHX58) is a negative regulator of the RIG-1 signalling pathway. In human, the DHX58 gene can be upregulated and can inhibit the RIG-1 signalling pathway during viral infection. In this study, porcine DHX58 gene expression patterns were studied. According to our results, the porcine DHX58 gene was upregulated not only by the stimulation of Poly I:C but also by the stimulation of 1ipopolysaccharides (LPS). One polymorphism (g.4919G>C), detected in the ninth intron, was significantly associated with some blood parameters including the red cell distribution width of 1-day-old pigs and white blood cell counts, lymphocyte absolute counts, and platelet distribution width of 17-day-old pigs (P < 0.05). Moreover, the individuals with the genotype GG have a significantly higher mean white blood cell count than individuals with genotype CC or GC (P < 0.05). Our study indicates that DHX58 is an important gene that is associated with the immune response in swine.