Brünnich's guillemots (Uria lomvia) maintain high temperature in the body core during dives

A major challenge for diving birds, reptiles, and mammals is regulating body temperature while conserving oxygen through a reduction in metabolic processes. To gain insight into how these needs are met, we measured dive depth and body temperatures at the core or periphery between the skin and abdominal muscles simultaneously in freely diving Brünnich's guillemots (Uria lomvia), an arctic seabird, using an implantable data logger (16-mm diameter, 50-mm length, 14-g mass, Little Leonardo Ltd., Tokyo). Guillemots exhibited increased body core temperatures, but decreased peripheral temperatures, during diving. Heat conservation within the body core appeared to result from the combined effect of peripheral vasoconstriction and a high wing beat frequency that generates heat. Conversely, the observed tissue hypothermia in the periphery should reduce metabolic processes as well as heat loss to the water. These physiological effects are likely one of the key physiological adaptations that makes guillemots to perform as an efficient predator in arctic waters.     

Isolation and characterization of the gene encoding a chitin synthase with a myosin motor-like domain from the edible basidiomycetous mushroom, <Emphasis Type="Italic">Lentinula edodes</Emphasis>, and its expression in the course of fruit-body formation

We isolated and characterized the genomic and complementary DNAs encoding a chitin synthase from an edible basidiomycetous mushroom, Lentinula edodes. The gene (which we designated Lechs1) contains a large open reading frame encoding a polypeptide of 1937 amino acid residues. The open reading frame is interrupted by 14 small introns (49–116 bp). The gene product (LeChs1) consists of a myosin motor-like domain in its N-terminal half and a chitin synthase domain in its C-terminal half, analogous to the class V and VI chitin synthases of other filamentous fungi. Phylogenetic analysis demonstrated that LeChs1 is classified into class VI chitin synthases. Southern blot analysis indicated that Lechs1 is a single-copy gene per haploid genome and that L. edodes has no other highly homologous chitin synthase genes. Northern blot analysis revealed that Lechs1 is expressed throughout the whole stages of fruit-body formation of L. edodes, but its expression level gradually declines in a fruit body-maturation-dependent manner with highest expression in vegetative mycelia and fruit body at the early stage of maturation (immature fruit body). This is the first report on the isolation and characterization of the gene encoding a chitin synthase with a myosin motor-like domain from basidiomycetes.     

Extra-embryonic endoderm cells derived from ES cells induced by GATA Factors acquire the character of XEN cells

Background  

Three types of cell lines have been established from mouse blastocysts: embryonic stem (ES) cells, trophoblast stem (TS) cells, and extra-embryonic endoderm (XEN) cells, which have the potential to differentiate into their respective cognate lineages. ES cells can differentiate in vitro not only into somatic cell lineages but into extra-embryonic lineages, including trophectoderm and extra-embryonic endoderm (ExEn) as well. TS cells can be established from ES cells by the artificial repression of Oct3/4 or the upregulation of Cdx2 in the presence of FGF4 on feeder cells. The relationship between these embryo-derived XEN cells and ES cell-derived ExEn cell lines remains unclear, although we have previously reported that overexpression of Gata4 or Gata6 induces differentiation of mouse ES cells into extra-embryonic endoderm in vitro.     

Relationship between sleep duration and cause-specific mortality in diabetic men and women based on self-reports

Sleep and Biological Rhythms - Sleep duration could affect glucose tolerance and mortality. However, the impact that sleep duration has on prognosis of people with diabetes is unclear. A cohort of...     

Lead generation of heat shock protein 90 inhibitors by a combination of fragment-based approach, virtual screening, and structure-based drug design

Heat shock protein 90 (Hsp90) is a molecular chaperone which regulates maturation and stabilization of its substrate proteins, known as client proteins. Many client proteins of Hsp90 are involved in tumor progression and survival and therefore Hsp90 can be a good target for developing anticancer drugs. With the aim of efficiently identifying a new class of orally available inhibitors of the ATP binding site of this protein, we conducted fragment screening and virtual screening in parallel against Hsp90. This approach quickly identified 2-aminotriazine and 2-aminopyrimidine derivatives as specific ligands to Hsp90 with high ligand efficiency. In silico evaluation of the 3D X-ray Hsp90 complex structures of the identified hits allowed us to promptly design CH5015765, which showed high affinity for Hsp90 and antitumor activity in human cancer xenograft mouse models.     

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.     

Receptor for advanced glycation end products binds to phosphatidylserine and assists in the clearance of apoptotic cells

Clearance of apoptotic cells is necessary for tissue development, homeostasis and resolution of inflammation. The uptake of apoptotic cells is initiated by an 'eat-me' signal, such as phosphatidylserine, on the cell surface and phagocytes recognize the signal by using specific receptors. In this study, we show that the soluble form of the receptor for advanced glycation end products (RAGE) binds to phosphatidylserine as well as to the apoptotic thymocytes. RAGE-deficient (Rage(-/-)) alveolar macrophages showed impaired phagocytosis of apoptotic thymocytes and defective clearance of apoptotic neutrophils in Rage(-/-) mice. Our results indicate that RAGE functions as a phosphatidylserine receptor and assists in the clearance of apoptotic cells.     

Designer TGFβ superfamily ligands with diversified functionality

Transforming Growth Factor--beta (TGFβ) superfamily ligands, including Activins, Growth and Differentiation Factors (GDFs), and Bone Morphogenetic Proteins (BMPs), are excellent targets for protein-based therapeutics because of their pervasiveness in numerous developmental and cellular processes. We developed a strategy termed RASCH (Random Assembly of Segmental Chimera and Heteromer), to engineer chemically-refoldable TGFβ superfamily ligands with unique signaling properties. One of these engineered ligands, AB208, created from Activin-βA and BMP-2 sequences, exhibits the refolding characteristics of BMP-2 while possessing Activin-like signaling attributes. Further, we find several additional ligands, AB204, AB211, and AB215, which initiate the intracellular Smad1-mediated signaling pathways more strongly than BMP-2 but show no sensitivity to the natural BMP antagonist Noggin unlike natural BMP-2. In another design, incorporation of a short N-terminal segment from BMP-2 was sufficient to enable chemical refolding of BMP-9, without which was never produced nor refolded. Our studies show that the RASCH strategy enables us to expand the functional repertoire of TGFβ superfamily ligands through development of novel chimeric TGFβ ligands with diverse biological and clinical values.