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

RETRACTED: The Chromatin-Remodeling Complex WINAC Targets a Nuclear Receptor to Promoters and Is Impaired in Williams Syndrome

This article has been retracted: please see Elsevier Policy on Article Withdrawal (http://www.elsevier.com/locate/withdrawalpolicy).This article has been retracted at the request of the Authors.Our paper reported that a chromatin-remodeling complex, WINAC, recruited the unliganded vitamin D receptor to promoters in cooperation with the transcription factor implicated in Williams syndrome, WSTF. The findings provided insights into the coordination between chromatin remodelers and sequence-specific transcription factors and pointed to a role of chromatin remodeling defects in Williams syndrome. We recently identified errors affecting several figure panels where original data were processed inappropriately such that the figure panels do not accurately report the original data. We believe that the most responsible course of action is to retract the paper. We sincerely apologize to the scientific community for any inconvenience that this might cause. The first author, H.K., declined to sign the retraction notice

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

The Japanese Clinical Practice Guidelines for Management of Sepsis and Septic Shock 2016 (J-SSCG 2016)

Background and purposeThe Japanese Clinical Practice Guidelines for Management of Sepsis and Septic Shock 2016 (J-SSCG 2016), a Japanese-specific set of clinical practice guidelines for sepsis and septic shock created jointly by the Japanese Society of Intensive Care Medicine and the Japanese Association for Acute Medicine, was first released in February 2017 and published in the Journal of JSICM, [2017; Volume 24 (supplement 2)] https://doi.org/10.3918/jsicm.24S0001 and Journal of Japanese Association for Acute Medicine [2017; Volume 28, (supplement 1)] http://onlinelibrary.wiley.com/doi/10.1002/jja2.2017.28.issue-S1/issuetoc.This abridged English edition of the J-SSCG 2016 was produced with permission from the Japanese Association of Acute Medicine and the Japanese Society for Intensive Care Medicine.MethodsMembers of the Japanese Society of Intensive Care Medicine and the Japanese Association for Acute Medicine were selected and organized into 19 committee members and 52 working group members. The guidelines were prepared in accordance with the Medical Information Network Distribution Service (Minds) creation procedures. The Academic Guidelines Promotion Team was organized to oversee and provide academic support to the respective activities allocated to each Guideline Creation Team. To improve quality assurance and workflow transparency, a mutual peer review system was established, and discussions within each team were open to the public. Public comments were collected once after the initial formulation of a clinical question (CQ) and twice during the review of the final draft. Recommendations were determined to have been adopted after obtaining support from a two-thirds (> 66.6%) majority vote of each of the 19 committee members.ResultsA total of 87 CQs were selected among 19 clinical areas, including pediatric topics and several other important areas not covered in the first edition of the Japanese guidelines (J-SSCG 2012). The approval rate obtained through committee voting, in addition to ratings of the strengths of the recommendation, and its supporting evidence were also added to each recommendation statement. We conducted meta-analyses for 29 CQs. Thirty-seven CQs contained recommendations in the form of an expert consensus due to insufficient evidence. No recommendations were provided for five CQs.ConclusionsBased on the evidence gathered, we were able to formulate Japanese-specific clinical practice guidelines that are tailored to the Japanese context in a highly transparent manner. These guidelines can easily be used not only by specialists, but also by non-specialists, general clinicians, nurses, pharmacists, clinical engineers, and other healthcare professionals

Remarks on the Phragmen-Lindelof theorem for Lp-viscosity solutions of fully nonlinear PDEs with unbounded ingredients

The Phragmen-Lindelof theorem for Lp-viscosity solutions of fully nonlinear second order elliptic partial differential equations with unbounded coefficients and inhomogeneous terms is established