Relation between dynamic heterogeneities observed in scattering experiments and four-body correlations

Dynamic heterogeneity is expected to be a key concept for understanding the origin of slow dynamics near the glass transition. In previous studies, quantitative evaluations of dynamic heterogeneity have been attempted using two different routes, i.e., the speckle patterns in scattering experiments or the four-body correlation functions of microscopic configuration data obtained from molecular dynamics simulations or real-space observations using confocal microscopy. However, the physical relationship between these dynamic heterogeneities obtained using different methods has not been clarified. This study proposes a connection between dynamic heterogeneities characterized based on speckle patterns and those obtained from four-body correlations. The validity of the relationship is also clarified.Comment: 6 pages, 5 figure

Pediatric airway compromise due to thyroid storm associated with influenza A infection: A case report

Thyroid storm is a potentially fatal intensification of thyrotoxicosis normally marked by tachycardia, hyperthermia, impaired mental status, and severe agitation. It can be initiated by numerous causes. Failure to promptly diagnose the condition may lead to high mortality. Early diagnosis and treatment of thyroid storm are essential to prevent further life-threatening complications. A 10-year-old girl was admitted to our emergency center for intensive care. The patient presented tachypnea with stridor, paradoxical abdominal breathing, and “barking” cough. The patient was diagnosed as upper airway obstruction complicated by thyroid storm associated with influenza infection. Following immediate airway management, the patient was administered a short-acting beta-blocker, hydrocortisone, thiamazole, and saturated solution of potassium iodide was initiated. The patient was extubated on day 8 and transferred to a local hospital on day 11 without adverse complications. When examining patients with influenza infection, emergency doctors should be more attentive not to miss other critical diagnoses. The present case was initially diagnosed as croup due to influenza infection. Sharing our experience may help emergency physicians treat similar cases of pediatric airway compromise due to thyroid storm

Invention of stimulus‐responsive peptide‐bond‐cleaving residue (Spr) and its application to chemical biology tools

Elucidation of biological functions of peptides and proteins is essential for understanding peptide/protein-related biological events and developing drugs. Caged peptides and proteins that release a parent active peptide/protein by photo-irradiation have successfully been employed to elucidate the functions. Whereas the usual caged peptide/protein enables conversion of an inactive form to an active form (OFF-to-ON conversion) by photo-induced deprotection, photo-triggered main chain cleavage is reported to be applicable to ON-to-OFF conversion. These peptides and proteins are photo-responsive; however, if peptides and proteins could respond to other stimuli such as disease-related environment or enzymes, their range of application should be widened. To convert the photo-responsive peptide/protein into other stimulus-responsive peptide/protein, quite laborious de novo design and synthesis of the stimulus-responsive unit are required. In this context, we designed a stimulus-responsive peptide-bond-cleaving residue (Spr) in which the stimuli available for the main chain cleavage vary according to the choice of protecting groups on the residue. In this review, design and synthesis of Spr are introduced, and challenges to apply Spr to other fields to enable, for example, functional control, localization control, delivery of cargos, labeling of a protein of interest in living cells, and identification of target proteins of bioactive ligands are discussed

Invention of stimulus‐responsive peptide‐bond‐cleaving residue (Spr) and its application to chemical biology tools

Elucidation of biological functions of peptides and proteins is essential for understanding peptide/protein-related biological events and developing drugs. Caged peptides and proteins that release a parent active peptide/protein by photo-irradiation have successfully been employed to elucidate the functions. Whereas the usual caged peptide/protein enables conversion of an inactive form to an active form (OFF-to-ON conversion) by photo-induced deprotection, photo-triggered main chain cleavage is reported to be applicable to ON-to-OFF conversion. These peptides and proteins are photo-responsive; however, if peptides and proteins could respond to other stimuli such as disease-related environment or enzymes, their range of application should be widened. To convert the photo-responsive peptide/protein into other stimulus-responsive peptide/protein, quite laborious de novo design and synthesis of the stimulus-responsive unit are required. In this context, we designed a stimulus-responsive peptide-bond-cleaving residue (Spr) in which the stimuli available for the main chain cleavage vary according to the choice of protecting groups on the residue. In this review, design and synthesis of Spr are introduced, and challenges to apply Spr to other fields to enable, for example, functional control, localization control, delivery of cargos, labeling of a protein of interest in living cells, and identification of target proteins of bioactive ligands are discussed

Efficacy of carotid thrombus penetration with a balloon guiding catheter to fast recanalization of acute extra- and intra-cranial carotid artery tandem occlusion

Acute ischemic stroke with ipsilateral Internal carotid artery (ICA) stenosis presents a great management dilemma. We present our preliminary report of retrograde retrieval of clot from middle cerebral artery (MCA) followed by delayed carotid artery stenting (CAS) with dual anti platelet therapy (DAPT)

Intravenous Administration of Bone Marrow-Derived Mesenchymal Stem Cell, but not Adipose Tissue-Derived Stem Cell, Ameliorated the Neonatal Hypoxic-Ischemic Brain Injury by Changing Cerebral Inflammatory State in Rat

Perinatal hypoxic-ischemic (HI) brain injury occurs in 1 in 1,000 live births and remains the main cause of neurological disability and death in term infants. Cytotherapy has recently emerged as a novel treatment for tissue injury. In particular, mesenchymal stem cells (MSCs) are thought to have therapeutic potential, but little is known about the differences according to their origin. In the current study, we investigated the therapeutic effects and safety of intravenous injection of allogeneic bone marrow-derived MSCs (BM-MSCs) and adipose-derived stem cells (ADSCs) in a rat model of HI brain injury. HI models were generated by ligating the left carotid artery of postnatal day 7 Wistar/ST rats and exposing them to 8% hypoxia for 60 min. Bone marrow and adipose tissue were harvested from adult green fluorescent protein transgenic Wistar rats, and cells were isolated and cultured to develop BM-MSCs and ADSCs. At passaging stages 2–3, 1 × 105 cells were intravenously injected into the external right jugular vein of the HI rats at 4 or 24 h after hypoxia. Brain damage was evaluated by counting the number of cells positive for active caspase-3 in the entire dentate gyrus. Microglial isotypes and serum cytokines/chemokines were also evaluated. Distribution of each cell type after intravenous injection was investigated pathologically and bio-optically by ex vivo imaging (IVIS®) with a fluorescent lipophilic tracer DiR. The mortality rate was higher in the ADSC group compared to the BM-MSC group, in pups injected with cells 4 h after hypoxia. The number of active caspase-3-positive cells significantly decreased in the BM-MSC group, and the percentage of M1 microglia (a proinflammatory isotype) was also lower in the BM-MSC vs control group in the penumbra of the cortex. Moreover, BM-MSC administration increased anti-inflammatory cytokine and growth factor levels, while ADSCs did not. Each injected cell type was mainly distributed in the lungs and liver, but ADSCs remained in the lungs longer. Pathologically, pulmonary embolisms and diffuse alveolar hemorrhages were seen in the ADSC group. These results indicated that injection of allogeneic BM-MSCs ameliorated neonatal HI brain injury, whereas ADSCs induced severe lung hemorrhage and higher mortality

Anemia Associated with Worse Outcome in Diffuse Large B-Cell Lymphoma Patients: A Single-Center Retrospective Study

Objective: Useful prognostic biomarkers for diffuse large B-cell lymphoma (DLBCL) patients have been reported. To determine the prognostic value of hemoglobin (Hb) level in DLBCL patients, we performed a retrospective study. Materials and Methods: We evaluated disease outcome, progressionfree survival (PFS), overall survival as the endpoint, and clinical and laboratory factors affecting the outcome of 185 DLBCL patients who had received rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone therapy during 2004-2014. Results: The study group included 121 men and 64 women with a median age of 66 years minimum-maximum: 21-83 years. In univariate analysis, factors independently associated with worse PFS were Eastern Cooperative Oncology Group performance status ≥2, Ann Arbor stage III or IV, anemia with Hb levels of <10 g/dL, and serum albumin of <3.5 g/ dL. In multivariate analysis, anemia with Hb levels of <10 g/dL and Ann Arbor stage III or IV were found to be international index-independent prognostic factors (hazard ratio: 2.4; p=0.04). Conclusion: Anemia is an independent prognostic marker of poor outcome in DLBCL patients. Hb can be an easily available prognostic marker for risk stratification in these patients

Labelling of Endogenous Target Protein via N–S Acyl Transfer-Mediated Activation of N-Sulfanylethylanilide

The ligand-dependent incorporation of a reporter molecule (e.g., fluorescence dye or biotin) onto a endogenous target protein has emerged as an important strategy for elucidating protein function using various affinity-based labelling reagents consisting of reporter, ligand and reactive units. Conventional labelling reagents generally use a weakly activated reactive unit, which can result in the non-specific labelling of proteins in a ligand-independent manner. In this context, the activation of a labelling reagent through a targeted protein-ligand interaction could potentially overcome the problems associated with conventional affinity-based labelling reagents. We hypothesized that this type of protein-ligand-interaction-mediated activation could be accomplished using N-sulfanylethylanilide (SEAlide) as the reactive unit in the labelling reagent. Electrophilically unreactive amide-type SEAlide can be activated by its conversion to the corresponding active thioester in the presence of a phosphate salt, which can act as an acid-base catalyst. It has been suggested that protein surfaces consisting of hydrophilic residues such as amino, carboxyl and imidazole groups could function as acid-base catalysts. We therefore envisioned that a SEAlide-based labelling reagent (SEAL) bearing SEAlide as a reactive unit could be activated through the binding of the SEAL with a target protein. Several SEALs were readily prepared in this study using standard 9-fluorenylmethyloxycarbonyl (Fmoc)-based solid-phase protocols. These SEAL systems were subsequently applied to the ligand-dependent labelling of human carbonic anhydrase (hCA) and cyclooxyganese 1. Although we have not yet obtained any direct evidence for the target protein-mediated activation of the SEAlide unit, our results for the reaction of these SEALs with hCA1 or butylamine indirectly support our hypothesis. The SEALs reported in this study represent valuable new entries to the field of affinity-based labelling reagents and are expected to show great utility in protein labelling