A Synthetic Multidomain Peptide That Drives a Macropinocytosis-Like Mechanism for Cytosolic Transport of Exogenous Proteins into Plants

Direct delivery of proteins into plants represents a promising alternative to conventional gene delivery for probing and modulating cellular functions without the risk of random integration of transgenes into the host genome. This remains challenging, however, because of the lack of a protein delivery tool applicable to diverse plant species and the limited information about the entry mechanisms of exogenous proteins in plant cells. Here, we present the synthetic multidomain peptide (named dTat-Sar-EED4) for cytosolic protein delivery in various plant species via simple peptide-protein coincubation. dTat-Sar-EED4 enabled the cytosolic delivery of an active enzyme with up to ∼20-fold greater efficiency than previously described cell-penetrating peptides in several model plant systems. Our analyses using pharmacological inhibitors and transmission electron microscopy revealed that dTat-Sar-EED4 triggered a unique endocytic mechanism for cargo protein internalization. This endocytic mechanism shares several features with macropinocytosis, including the dependency of actin polymerization, sensitivity to phosphatidylinositol-3 kinase activity, and formation of membrane protrusions and large intracellular vesicles (>200 nm in diameter), even though macropinocytosis has not been identified to date in plants. Our study thus presents a robust molecular tool that can induce a unique cellular uptake mechanism for the efficient transport of bioactive proteins into plants

Clinical relevance of impaired consciousness in accidental hypothermia: a Japanese multicenter retrospective study

[Aim] This study aimed to investigate the association between level of impaired consciousness and severe hypothermia (<28°C) and to evaluate the association between level of impaired consciousness and inhospital mortality among accidental hypothermia patients. [Methods] This was a multicenter retrospective study using the J-Point registry database, which includes data regarding patients whose core body temperature was 35.0°C or less and who were treated as accidental hypothermia in emergency departments between April 1, 2011 and March 31, 2016. We estimated adjusted odds ratios of the level of impaired consciousness for severe hypothermia less than 28°C and inhospital mortality using a logistic regression model. [Results] The study included 505 of 572 patients in the J-Point registry. Relative to mildly impaired consciousness (Glasgow Coma Scale [GCS] 13–15), the adjusted odds ratios for severe hypothermia less than 28°C were: moderate (GCS 9–12), 3.26 (95% confidence interval [CI], 1.69–6.25); and severe (GCS < 9), 4.68 (95% CI, 2.40–9.14). Relative to mildly impaired consciousness (GCS 13–15), the adjusted odds ratios for inhospital mortality were: moderate (GCS9–12), 1.65 (95% CI, 0.95–2.88); and severe (GCS < 9), 2.10 (95% CI, 1.17–3.78). [Conclusion] The level of impaired consciousness in patients with accidental hypothermia was associated with severe hypothermia and inhospital mortality

Effects of low-temperature capping on the optical properties of GaAs/AlGaAs quantum wells

We study the effects of low-temperature capping (200-450°C) on the optical properties of GaAs/AlGaAs quantum wells. Photoluminescence measurements clearly show the formation of abundant nonradiative recombination centers in an AlGaAs capping layer grown at 200°C, while there is a slight degradation of the optical quality in AlGaAs capping layers grown at temperatures above 350°C compared to that of a high-temperature capping layer. In addition, the optical quality can be restored by post-growth annealing without any structural change, except for the 200°C-capped sample

ANALISIS PUTUSAN HAKIM NOMOR 41/PID.SUS/2018/PN BATU LICIN, TENTANG PERKARA SEDIAAN FARMASI OBAT DAFTAR G JENIS CARNOPEN YANG TIDAK MEMILIKI IJIN DITINJAU DARI ASPEK KEADILAN

The main task of the judge is to accept, examine and try and settle every case submitted to him. It seems very simple for the judge's duties as referred to in Article 2 paragraph 1 of Law Number 48 of 2009, but in reality it is not easy and that simple. The formulation of the problem in this study is 1) What is the Basic Consideration of Judge Judge Number 41 / Pid.Sus / 2018 / PN Batu Licin about the case of circulating pharmaceutical preparations for the list of G types of carnopen that do not have permission? 2) How is the Decision Number 41 / Pid.Sus / 2018 / PN Batu Licin concerning the case of circulating pharmaceutical preparations of the list of drugs G type carnopen that do not have permission in terms of aspects of justice? The approach used in this writing is normative juridical. The data used in this study are primary and secondary data. Analysis of legal materials used in this study is descriptive quality. The results of the analysis show that the basis for the Judgment of Judge Number 41 / Pid.Sus / 2018 / PN Batu Licin about the case of circulating pharmaceutical drug preparations list G types of carnopen which do not have permission, namely subjectively in this case, which is concerning a priori behavioral attitudes, behavioral attitudes emotional, arrogant and moral attitude. Objectively, that is regarding social, cultural and economic backgrounds, professionally. Decision Number 41 / Pid.Sus / 2018 / PN Batu Licin concerning cases circulating pharmaceutical preparations of the list of G types of carnopen which do not have permission in terms of justice, namely 1) declaring the aforementioned Defendant Candra Bin Rahmadi legally and convincingly guilty committing a criminal offense "intentionally circulating Pharmaceutical preparations that do not have marketing authorization" as in the primary indictment 2) Imposing a sentence to the Defendant because of that with imprisonment for 1 (one) year and 2 (two) months and a fine of Rp.2,000,000 00 (two million rupiahs) with the provision that if the fine is not paid is replaced by a confinement for 1 (one) month; and 3) Determine the period of arrest and detention that has been carried out by the Defendant entirely deducted from the sentence imposed

Early development of human hematopoietic and acquired immune systems in new born NOD/Scid/Jak3null mice intrahepatic engrafted with cord blood-derived CD34+ cells

An animal model in which the human immune system can be reconstituted is necessary to study acquired immunity in vivo. We report here a novel model, the NOD/SCID/JAK3null mouse, for the human immune system\u27s development. Newborn mice transplanted with human cord blood CD34+ cells intrahepatically, developed human T and B cells, and myeloid and plasmacytoid dendritic cells. The T and B cells had a naïve to memory phenotype, and included plasma cells. The human acquired immune system can be reconstituted from CD34+ cells in NOD/SCID/JAK3null mice. This model is a powerful tool for the study of human immunity

Osborn Wave Is Related to Ventricular Fibrillation and Tachycardia in Hypothermic Patients

Nobunaga Okada, Tasuku Matsuyama, Sachiko Morita, Naoki Ehara, Nobuhiro Miyamae, Yohei Okada, Takaaki Jo, Yasuyuki Sumida, Makoto Watanabe, Masahiro Nozawa, Ayumu Tsuruoka, Yoshihiro Fujimoto, Yoshiki Okumura, Kunio Hamanaka, Tetsuhisa Kitamura, Kei Nishiyama, Bon Ohta, Osborn Wave Is Related to Ventricular Fibrillation and Tachycardia in Hypothermic Patients, Circulation Journal, 2020, Volume 84, Issue 3, Pages 445-455, Released February 25, 2020, [Advance publication] Released January 30, 2020, Online ISSN 1347-4820, Print ISSN 1346-9843, https://doi.org/10.1253/circj.CJ-19-0856, https://www.jstage.jst.go.jp/article/circj/84/3/84_CJ-19-0856/_article/-char/e

RHO Mutations (p.W126L and p.A346P) in Two Japanese Families with Autosomal Dominant Retinitis Pigmentosa

Purpose. To investigate genetic and clinical features of patients with rhodopsin (RHO) mutations in two Japanese families with autosomal dominant retinitis pigmentosa (adRP). Methods. Whole-exome sequence analysis was performed in ten adRP families. Identified RHO mutations for the cosegregation analysis were confirmed by Sanger sequencing. Ophthalmic examinations were performed to evaluate the RP phenotypes. The impact of the RHO mutation on the rhodopsin conformation was examined by molecular modeling analysis. Results. In two adRP families, we identified two RHO mutations (c.377G>T (p.W126L) and c.1036G>C (p.A346P)), one of which was novel. Complete cosegregation was confirmed for each mutation exhibiting the RP phenotype in both families. Molecular modeling predicted that the novel mutation (p.W126L) might impair rhodopsin function by affecting its conformational transition in the light-adapted form. Clinical phenotypes showed that patients with p.W126L exhibited sector RP, whereas patients with p.A346P exhibited classic RP. Conclusions. Our findings demonstrated that the novel mutation (p.W126L) may be associated with the phenotype of sector RP. Identification of RHO mutations is a very useful tool for predicting disease severity and providing precise genetic counseling