Contribution of the LIM Domain and Nebulin-Repeats to the Interaction of Lasp-2 with Actin Filaments and Focal Adhesions

Lasp-2 binds to actin filaments and concentrates in the actin bundles of filopodia and lamellipodia in neural cells and focal adhesions in fibroblastic cells. Lasp-2 has three structural regions: a LIM domain, a nebulin-repeat region, and an SH3 domain; however, the region(s) responsible for its interactions with actin filaments and focal adhesions are still unclear. In this study, we revealed that the N-terminal fragment from the LIM domain to the first nebulin-repeat module (LIM-n1) retained actin-binding activity and showed a similar subcellular localization to full-length lasp-2 in neural cells. The LIM domain fragment did not interact with actin filaments or localize to actin filament bundles. In contrast, LIM-n1 showed a clear subcellular localization to filopodial actin bundles. Although truncation of the LIM domain caused the loss of F-actin binding activity and the accumulation of filopodial actin bundles, these truncated fragments localized to focal adhesions. These results suggest that lasp-2 interactions with actin filaments are mediated through the cooperation of the LIM domain and the first nebulin-repeat module in vitro and in vivo. Actin filament binding activity may be a major contributor to the subcellular localization of lasp-2 to filopodia but is not crucial for lasp-2 recruitment to focal adhesions

The Blimp1–Bcl6 axis is critical to regulate osteoclast differentiation and bone homeostasis

Controlling osteoclastogenesis is critical to maintain physiological bone homeostasis and prevent skeletal disorders. Although signaling activating nuclear factor of activated T cells 1 (NFATc1), a transcription factor essential for osteoclastogenesis, has been intensively investigated, factors antagonistic to NFATc1 in osteoclasts have not been characterized. Here, we describe a novel pathway that maintains bone homeostasis via two transcriptional repressors, B cell lymphoma 6 (Bcl6) and B lymphocyte–induced maturation protein-1 (Blimp1). We show that Bcl6 directly targets ‘osteoclastic’ molecules such as NFATc1, cathepsin K, and dendritic cell-specific transmembrane protein (DC-STAMP), all of which are targets of NFATc1. Bcl6-overexpression inhibited osteoclastogenesis in vitro, whereas Bcl6-deficient mice showed accelerated osteoclast differentiation and severe osteoporosis. We report that Bcl6 is a direct target of Blimp1 and that mice lacking Blimp1 in osteoclasts exhibit osteopetrosis caused by impaired osteoclastogenesis resulting from Bcl6 up-regulation. Indeed, mice doubly mutant in Blimp1 and Bcl6 in osteoclasts exhibited decreased bone mass with increased osteoclastogenesis relative to osteoclast-specific Blimp1-deficient mice. These results reveal a Blimp1–Bcl6–osteoclastic molecule axis, which critically regulates bone homeostasis by controlling osteoclastogenesis and may provide a molecular basis for novel therapeutic strategies

Functional Analyses of a Neural Cell Specific Variant of Microtubule-Associated Protein 4

The present study was conducted to analyze the functions of a recently reported neural cell specific variant of MAP4 (MAP4-SP) that lacks 72 consecutive amino acid residues in a region that is rich in proline and basic residues (pro-rich region). Although our previous study (Matsushima et al., 2005)^, using the microtubule-binding domains of the isoform and wild type MAP4 (MAP4-LP), demonstrated a difference in the microtubule bundling activity of the two proteins, here, using the full-length forms of the MAP4 proteins, we show that the proteins do not differ in their microtubule bundling activity both in vitro and in vivo. Expression of the MAP4 proteins, as C-terminal fusions to green fluorescent protein (GFP), in neuroblastoma cells revealed that MAP4-SP decorated microtubules were more remarkable in appearance than MAP4-LP decorated microtubules in the neuronal growth cones. Moreover, a microtubule destabilizing protein, septin2, which interacts with the pro-rich region of MAP4, was more active in destabilizing MAP4-SP-microtubules than MAP4-LP-microtubules in vitro. The susceptibility of MAP4-SP microtubules to destabilization by septin could be attributed to the weaker binding affinity of MAP4-SP for microtubules, as was reported earlier. Taken together, the current findings suggest the possibility that the neural MAP4, with its short pro-rich region, could be important in maintaining more dynamic microtubules in neural cells, and thus allowing more plasticity in and rapid morphological changes of these cells

S (2010) Derivation of a yearly transition probability matrix for land-use dynamics and its applications. Landscape Ecology 25: 561–572

Abstract Transition matrices have often been used in landscape ecology and GIS studies of land-use to quantitatively estimate the rate of change. When transition matrices for different observation periods are compared, the observation intervals often differ because satellite images or photographs of the research site taken at constant time intervals may not be available. If the observation intervals differ, the transition probabilities cannot be compared without calculating a transition matrix with the normalized observation interval. For such calculation, several previous studies have utilized a linear algebra formula of the power root of matrices. However, three difficulties may arise when applying this formula to a practical dataset from photographs of a research site. We examined the first difficulty, namely that plural solutions could exist for a yearly transition matrix, which implies that there could be multiple scenarios for the same transition in land-use change. Using data for the Abukuma Mountains in Japan and the Selva el Ocote Biosphere Reserve in Mexico, we then looked at the second difficulty, in which we may obtain no positive Markovian matrix and only a matrix partially consisting of negative numbers. We propose a way to calibrate a matrix with some negative transition elements and to estimate the prediction error. Finally, we discuss the third difficulty that arises when a new land-use category appears at the end of the observation period and how to solve it. We developed a computer program to calculate and calibrate the yearly matrices and to estimate the prediction error

A SYNDROME RESEMBLING HOMOLOGOUS DISEASE AFTER SHORT-TERM CROSS-CIRCULATION IN RABBITS

この論文は国立情報学研究所の学術雑誌公開支援事業により電子化されました。1. Cross circulation between pairs of white mature rabbits was performed. Disregarding the time of death, one partner of most pairs died after cross circulation and in all the rabbits that died similar symptoms consisting of sudden onset of diarrhoea, erection of body hair, weight loss etc. were seen and death took place within a few days after onset of these symptoms. 2. This syndrome was clinically similar to homologous disease in some respects, but several points of difference were noted and demand further study

Postintensive care syndrome family: A comprehensive review.

Publication status: PublishedFamilies of critically ill patients are predisposed to tremendous burdens when their relatives are admitted to the intensive care unit (ICU). Postintensive care syndrome family (PICS-F) can be described as a devastated life, encompassing psychological, physical, and socioeconomical burdens that begin with the emotional impact experienced by the family when the patient is admitted to the ICU. PICS-F was primarily proposed as a clinically significant psychological impairment, but it needs to be extended beyond the psychological impairment of the family to include physical and socioeconomical impairments in the future. The prevalence of physiological problems including depression, anxiety and post-traumatic syndrome is 20-40%, and that of non-physiological problems including fatigue is 15% at 6 months after the ICU stay. Assessment of PICS-F was frequently conducted at 3- or 6-month points, although the beginning of the evaluation was based on different assessment points among each of the studies. Families of ICU patients need to be given and understand accurate information, such as the patient's diagnosis, planned care, and prognosis. Prevention of PICS-F requires a continuous bundle of multifaceted and/or multidisciplinary interventions including providing a family information leaflet, ICU diary, communication facilitators, supportive grief care, and follow-up, for the patient and families from during the ICU stay to after discharge from the ICU. This is the first comprehensive review of PICS-F to address the concept, risk factors, assessment tools, prevalence, and management to prevent PICS-F to facilitate acute care physicians' understanding of PICS-F