Pharmacological Evaluation of SKL-18287, a New Long-Acting Glucagon-Like Peptide-1 Receptor Agonist with Enhanced Aggregation Propensity,in Rodent Models

International Journal of Peptide Research and Therapeutics - Very recently, we have reported a new glucagon-like peptide-1 (GLP-1) receptor agonist, SKL-18287, (EC50: 1.2 and 0.13 nM for...     

Fine needle aspiration of toxoplasmic lymphadenitis in an intramammary lymph node. A case report

BACKGROUND: Cytologic findings of toxoplasmic lymphadenitis (TL) have been only sporadically reported. Intramammary lymph node is an extremely rare site for TL. CASE: A 47-year-old, healthy, female presented with a breast tumor, which was aspirated. The cytomorphologic features were interpreted as suggestive of TL. Histopathology of the excisional biopsy specimen and subsequent serologic examination confirmed the diagnosis. CONCLUSION: We obtained several characteristic findings in aspiration of TL. Of these, epithelioid cell clusters and monocytoid cells were the most diagnostic.     

Direct interaction of Ski with either Smad3 or Smad4 is necessary and sufficient for Ski-mediated repression of transforming growth factor-beta signaling

The oncoprotein Ski represses transforming growth factor (TGF)-beta signaling in an N-CoR-independent manner. However, the molecular mechanism(s) underlying this event has not been elucidated. Here, we identify an additional domain in Ski that mediates interaction with Smad3 which is important for this repression. This domain is distinct from the previously reported N-terminal Smad3 binding domain in Ski. Individual alanine substitution of several residues in the domain significantly affected Ski-Smad3 interaction. Furthermore, combined mutations within this domain, together with those in the previously identified Smad3 binding domain, can completely abolish the interaction of Ski with Smad3, while mutation in each domain alone retained partial interaction. By introducing those mutations that abolish direct interaction with Smad3 or Smad4 individually, or in combination, we show that interaction of Ski with either Smad3 or Smad4 is sufficient for Ski-mediated repression of TGF-beta signaling. Furthermore our results clearly demonstrate that Ski does not disrupt Smad3-Smad4 heteromer formation, and recruitment of Ski to the Smad3/4 complex through binding to either Smad3 or Smad4 is both necessary and sufficient for repression.     

Origins of globular structure in proteins

Since natural proteins are the products of a long evolutionary process, the structural properties of present-day proteins should depend not only on physico-chemical constraints, but also on evolutionary constraints. Here we propose a model for protein evolution, in which membranes play a key role as a scaffold for supporting the gradual evolution from flexible polypeptides to well-folded proteins. We suggest that the folding process of present-day globular proteins is a relic of this putative evolutionary process. To test the hypothesis that membranes once acted as a cradle for the folding of globular proteins, extensive research on membrane proteins and the interactions of globular proteins with membranes will be required.     

Hematology and serum biochemistry in debilitated, free-ranging raccoon dogs (Nyctereutes procyonoides) infested with sarcoptic mange

Frequent outbreaks of Sarcoptes scabiei infestation in raccoon dogs (Nyctereutes procyonoides) have been reported in Japan. Although many raccoon dogs are brought to Kanazawa Zoological Garden (Yokohama, Kanagawa, Japan) because of S. scabiei infestation and debilitation, some of them die of asthenia. The clinical status of severely debilitated raccoon dogs must be determined to save their lives. In this study, we compared hematological and serum biochemical values between severely debilitated and nondebilitated raccoon dogs infested with S. scabiei. The total protein, albumin, glucose, and calcium values of debilitated raccoon dogs were significantly lower than those of nondebilitated raccoon dogs. On the other hand, debilitated raccoon dogs had significantly higher aspartate aminotransferase, total bilirubin, blood urea nitrogen, sodium, chloride, and phosphorus values than did nondebilitated raccoon dogs. The increase in the blood urea nitrogen value was particularly dramatic. The present study revealed that debilitated raccoon dogs infested with S. scabiei exhibited abnormal hematological values compared with nondebilitated raccoon dogs infested with S. scabiei. Clinically, the raccoon dogs developed malnutrition and sepsis if the mange infestation was untreated. Moreover, dehydration associated with appetite loss may have resulted in insufficient renal perfusion. These findings suggest that chronic S. scabiei infestations debilitated the raccoon dogs and resulted in physiological changes that were detected with hematological and serum biochemical tests.