The Drosophila AWP1 ortholog Doctor No regulates JAK/STAT signaling for left-right asymmetry in the gut by promoting receptor endocytosis.

Many organs of Drosophila show stereotypical left-right (LR) asymmetry; however, the underlying mechanisms remain elusive. Here, we have identified an evolutionarily conserved ubiquitin-binding protein, AWP1/Doctor No (Drn), as a factor required for LR asymmetry in the embryonic anterior gut. We found that drn is essential in the circular visceral muscle cells of the midgut for JAK/STAT signaling, which contributes to the first known cue for anterior gut lateralization via LR asymmetric nuclear rearrangement. Embryos homozygous for drn and lacking its maternal contribution showed phenotypes similar to those with depleted JAK/STAT signaling, suggesting that Drn is a general component of JAK/STAT signaling. Absence of Drn resulted in specific accumulation of Domeless (Dome), the receptor for ligands in the JAK/STAT signaling pathway, in intracellular compartments, including ubiquitylated cargos. Dome colocalized with Drn in wild-type Drosophila. These results suggest that Drn is required for the endocytic trafficking of Dome, which is a crucial step for activation of JAK/STAT signaling and the subsequent degradation of Dome. The roles of AWP1/Drn in activating JAK/STAT signaling and in LR asymmetric development may be conserved in various organisms.

E and ID proteins regulate cell chirality and left-right asymmetric development in Drosophila.

How left-right (LR) asymmetric forms in the animal body is a fundamental problem in Developmental Biology. Although the mechanisms for LR asymmetry are well studied in some species, they are still poorly understood in invertebrates. We previously showed that the intrinsic LR asymmetry of cells (designated as cell chirality) drives LR asymmetric development in the Drosophila embryonic hindgut, although the machinery of the cell chirality formation remains elusive. Here, we found that the Drosophila homologue of the Id gene, extra macrochaetae (emc), is required for the normal LR asymmetric morphogenesis of this organ. Id proteins, including Emc, are known to interact with and inhibit E-box-binding proteins (E proteins), such as Drosophila Daughterless (Da). We found that the suppression of da by wild-type emc was essential for cell chirality formation and for normal LR asymmetric development of the embryonic hindgut. Myosin ID (MyoID), which encodes the Drosophila Myosin ID protein, is known to regulate cell chirality. We further showed that Emc-Da regulates cell chirality formation, in which Emc functions upstream of or parallel to MyoID. Abnormal Id-E protein regulation is involved in various human diseases. Our results suggest that defects in cell shape may contribute to the pathogenesis of such diseases.

Effect of Daily Multidisciplinary Team Reflection in Ambulatory Care: A Qualitative Analysis.

PURPOSE: Research suggests that daily previsit team huddling leads to improved teamwork, however there are no reports on the effect and mechanism of daily team reflection in primary care practice. To help healthcare professionals to integrate fragmented information and to enhance continuity, we previously developed and implemented a daily multidisciplinary team reflection (DMDTR) approach. The present study aimed to construct a conceptual diagram illustrating how participation in DMDTR influence medical care in an ambulatory clinic. PARTICIPANTS AND METHODS: In this qualitative study, we analyzed data from semi-structured interviews (n = 12) conducted with physicians, nurses, and medical assistants who regularly participated in DMDTR. Modified grounded theory approach (M-GTA) was adopted as the analysis method, and structure-construction qualitative research method (SCQRM) was used as a meta-theory to determine the number of cases correlatively with the research objectives. RESULTS: Our conceptual diagram demonstrated that, through DMDTR, team members shared fragmented information to gain a more holistic view of the patient and discuss diverse points of view, a process that resulted in real-time problem solving through collaboration. This team approach showed benefit to each discipline and improves the care attributes of contextuality, coordination, accessibility, accountability, continuity, and comprehensiveness of care. CONCLUSION: We generated a conceptual diagram showing that DMDTR embodies a team approach that leads to improved care attributes, which results in enhanced quality of primary care.

Thiamethoxam intoxication due to occupational inhalational exposure.

Neonicotinoid is a new class of systemic insecticides that are selectively toxic to insects. However, cases of human toxicity have been reported. A man in his 60s, who worked as a pest control operator (which required the use of thiamethoxam), presented with fever and headache. We investigated the levels of thiamethoxam and clothianidin in the blood and urine. Our results suggested that chronic thiamethoxam intoxication was caused by occupational inhalation exposure and environmental pollution. After cessation of insecticide use, the patient remained asymptomatic but had persistent oral dysesthesia and postural finger tremor, even at undetectable levels of thiamethoxam and clothianidin. This case report is the first to describe human thiamethoxam intoxication after occupational inhalation exposure. When similar symptoms are encountered and a history of insecticide use is confirmed, clinicians should consider the diagnosis of neonicotinoid intoxication.

Transient global amnesia with bilateral hippocampal lesions during the COVID-19 global outbreak.

This manuscript presents a case report of transient global amnesia with bilateral hippocampal lesions which might be triggered by the fear of getting infected by coronavirus disease 2019 (COVID-19). The purpose of this article is to facilitate the clinicians in understanding that an increasing number of patients with transient global amnesia have been reported during the COVID-19 global outbreak.

N-Boc-Indolylbenzothiadiazole Derivatives: Efficient Full-Color Solid-State Fluorescence and Self-Recovering Mechanochromic Luminescence.

Herein, the solid-state emission with good fluorescence quantum yields of N-Boc-indolylbenzothiadiazoles as a new class of fluorophores is described. Their solid-state emission covers the wide range of the visible spectrum and the emission color can be tuned easily by changing the substituents on the two heteroaromatic rings. Among these, 3-methylindolyl derivatives exhibit moreover autonomously self-recovering mechanochromic luminescence, whereby the original solid-state emission could be recovered spontaneously at room temperature after exposure to a mechanical stimulus. The emission color, as well as the recovery time for the color change could be tuned via the introduction of different substituents on the benzothiadiazole ring. We propose that the mechanism of the autonomously self-recovering mechanochromic luminescence of 3-methylindolylbenzothiadiazoles is based on a partial amorphization of the crystals upon exposure to the mechanical stimulus, followed by autonomous recovering in the form of recrystallization.

A new method for alveolar bone repair using extracted teeth for the graft material.

BACKGROUND: In the clinical field of jawbone formation, the use of autogenous bone as the graft material is the gold standard. However, there are some problems with this technique, such as risk of infection on the donor side, the limited amount of available bone mass, and marked resorption of the grafted bone. We investigated the potential for using teeth as a bone graft material for jawbone formation because the dental pulp contains stem cells, including undifferentiated neural crest-derived cells. METHODS: Alveolar bone defects were created in Wistar rats, and the defects were filled with either tooth or iliac bone graft material, or left as controls. The potential for using teeth as a bone graft material for jawbone formation was measured using real-time polymerase chain reaction, microcomputed tomography, and histologic analysis. RESULTS: Polymerase chain reaction revealed that the expressions of P75, P0, nestin, and musashi-1 were significantly higher in teeth than in mandibular bone and iliac bone grafts. Hematoxylin and eosin staining and microcomputed tomography showed that at 8 weeks, tooth graft material produced a similar amount of new bone compared to iliac bone graft material. Osteopontin was expressed in both the tooth and iliac bone graft material at 6 and 8 weeks after surgery. Dentin sialoprotein was expressed in the tooth graft material in the new bone at 6 weeks only. CONCLUSION: These results indicate that teeth may be an alternative material to autogenous bone for treating alveolar bone defects by grafting.

Beta-fructofuranosidase genes of the silkworm, Bombyx mori: insights into enzymatic adaptation of B. mori to toxic alkaloids in mulberry latex.

Mulberry latex contains extremely high concentrations of alkaloidal sugar mimic glycosidase inhibitors, such as 1,4-dideoxy-1,4-imino-D-arabinitol (D-AB1) and 1-deoxynojirimycin (DNJ). Although these compounds do not harm the silkworm, Bombyx mori, a mulberry specialist, they are highly toxic to insects that do not normally feed on mulberry leaves. D-AB1 and DNJ are strong inhibitors of alpha-glucosidases (EC 3.2.1.20); however, they do not affect the activity of beta-fructofuranosidases (EC 3.2.1.26). Although alpha-glucosidase genes are found in a wide range of organisms, beta-fructofuranosidase genes have not been identified in any animals so far. In this study, we report the identification and characterization of beta-fructofuranosidase genes (BmSuc1 and BmSuc2) from B. mori. The BmSuc1 gene was highly expressed in the midgut and silk gland, whereas the expression of BmSuc2 gene was not detected. BmSuc1 encodes a functional beta-fructofuranosidase, whose enzymatic activity was not inhibited by DNJ or D-AB1. We also showed that BmSUC1 protein localized within the midgut goblet cell cavities. Collectively, our data clearly demonstrated that BmSuc1 serves as a sugar-digesting enzyme in the silkworm physiology. This anomalous presence of the beta-fructofuranosidase gene in the B. mori genome may partly explain why the silkworm can circumvent the mulberry's defense system.

Identification of GFAP gene mutation in hereditary adult-onset Alexander's disease.

Alexander's disease, a leukodystrophy characterized by Rosenthal fibers (RFs) in the brain, is categorized into three subtypes: infantile, juvenile, and adult. Although most are sporadic, occasional familial Alexander's disease cases have been reported for each subtype. Hereditary adult-onset Alexander's disease shows progressive spastic paresis, bulbar or pseudobulbar palsy, palatal myoclonus symptomatologically, and prominent atrophy of the medulla oblongata and upper spinal cord on magnetic resonance imaging. Recent identification of GFAP gene mutations in the sporadic infantile- and juvenile-onset Alexander's disease prompted us to examine the GFAP gene in two Japanese hereditary adult-onset Alexander's disease brothers with autopsy in one case. Both had spastic paresis without palatal myoclonus, and magnetic resonance imaging showed marked atrophy of the medulla oblongata and cervicothoracic cord. The autopsy showed severely involved shrunken pyramids, but scarce Rosenthal fibers (RFs). Moderate numbers of Rosenthal fibers (RFs) were observed in the stratum subcallosum and hippocampal fimbria. In both cases, we found a novel missense mutation of a G-to-T transition at nucleotide 841 in the GFAP gene that results in the substitution of arginine for leucine at amino acid residue 276 (R276L). This is the first report of identification of the causative mutation of the GFAP gene for neuropathologically proven hereditary adult-onset Alexander's disease, suggesting a common molecular mechanism underlies the three Alexander's disease subtypes.