Development of icterus gravis in a preterm infant with G71R UGT1A1 polymorphism

BACKGROUND: Uridine diphosphate-glucuronosyltransferase (UGT) gene family is involved in the detoxification of biomaterials and drugs in the liver. Among the UGT gene family members, only UGT1A1 is involved in bilirubin conjugation. As a result, deficient UGT1A1 activity causes jaundice. One disease that is characterized by reduced UGT1A1 activity is Gilbert’s syndrome. Two prevalent UGT1A1 polymorphisms responsible for Gilbert’s syndrome have been identified: G71R in exon 1 and A(TA)7TAA in the TATA box of the promoter region. Recently, the G71R polymorphism has been associated with breastfeeding jaundice and neonatal hyperbilirubinemia in term infants. However, its association with jaundice in very low birth weight infants (VLBWIs) has never been reported. CASE PRESENTATION: The patient was a female born at 28 weeks, 4 days gestation with a birth weight of 1172 g. On day 21, intense yellowing of the skin and eyes was noted, and the patient’s total bilirubin level was 23.7 mg/dL (her direct bilirubin level was 2.1 mg/dL). Therefore, an exchange transfusion was conducted. She had neither blood type incompatibility nor a family history of constitutional jaundice. Metabolic screens for amino and organic acids were negative. No elevation of any of the examined antibody titers was noted, and no evidence of an inflammatory reaction was observed. In addition, no hematological abnormalities were detected. The direct/indirect Coombs test, irregular antibody test and red blood cell antibody dissociation test were all negative, and her thyroid function was normal. We performed sequence analysis of the UGT1A1 gene after the patient’s parents provided written informed consent. Exon 1 of the UGT1 gene on chromosome 2 was analyzed by direct sequencing. A heterozygous substitution from G to A (211G→A: G71R) in base 211 was noted. CONCLUSION: We speculated that this preterm infant with carrying the G71R polymorphism reduced UGT1A1 activity and developed severe jaundice that was likely triggered by factors such as breast feeding and medications. The polymorphism appears at some frequency among VLBWIs, which would necessitate adequate care of severe jaundice even after the acute phase

Direct Observation of the Myosin Va Recovery Stroke That Contributes to Unidirectional Stepping along Actin

Myosins are ATP-driven linear molecular motors that work as cellular force generators, transporters, and force sensors. These functions are driven by large-scale nucleotide-dependent conformational changes, termed “strokes”; the “power stroke” is the force-generating swinging of the myosin light chain–binding “neck” domain relative to the motor domain “head” while bound to actin; the “recovery stroke” is the necessary initial motion that primes, or “cocks,” myosin while detached from actin. Myosin Va is a processive dimer that steps unidirectionally along actin following a “hand over hand” mechanism in which the trailing head detaches and steps forward ∼72 nm. Despite large rotational Brownian motion of the detached head about a free joint adjoining the two necks, unidirectional stepping is achieved, in part by the power stroke of the attached head that moves the joint forward. However, the power stroke alone cannot fully account for preferential forward site binding since the orientation and angle stability of the detached head, which is determined by the properties of the recovery stroke, dictate actin binding site accessibility. Here, we directly observe the recovery stroke dynamics and fluctuations of myosin Va using a novel, transient caged ATP-controlling system that maintains constant ATP levels through stepwise UV-pulse sequences of varying intensity. We immobilized the neck of monomeric myosin Va on a surface and observed real time motions of bead(s) attached site-specifically to the head. ATP induces a transient swing of the neck to the post-recovery stroke conformation, where it remains for ∼40 s, until ATP hydrolysis products are released. Angle distributions indicate that the post-recovery stroke conformation is stabilized by ≥5 kBT of energy. The high kinetic and energetic stability of the post-recovery stroke conformation favors preferential binding of the detached head to a forward site 72 nm away. Thus, the recovery stroke contributes to unidirectional stepping of myosin Va

The practice of child and adolescent psychiatry: a survey of early-career psychiatrists in Japan

<p>Abstract</p> <p>Background</p> <p>Child and adolescent psychiatry (CAP), a subspecialty of psychiatry in Japan, is facing a serious workforce shortage. To resolve this situation, the Japanese government has organized a task force and has been working to increase psychiatrists' clinical skills to improve care for children and adolescents with mental health problems. Using an online questionnaire system, the authors have conducted a survey to investigate the perceptions, experiences, and interests of early-career psychiatrists in CAP.</p> <p>Methods</p> <p>The subjects of this study were 182 psychiatrists in Japan whose individual clinical experiences did not exceed 15 years. The authors of this study created an online questionnaire system and e-mailed the URL and login password to all subjects. Respondents anonymously answered the questions. Most questions required an answer indicating a level of agreement scored on a nine-point scale. Responding to the questionnaire was considered to constitute consent, and all respondents' privacy was carefully protected.</p> <p>Results</p> <p>The mean age and clinical psychiatric experience of the subjects were found to be 33.1 ± 4.5 years and 5.43 ± 3.5 years, respectively. On a nine-point scale (with nine being the highest), experience and interest in CAP measured 3.05 ± 1.9 and 5.34 ± 2.5, respectively; further, these two factors showed significant correlation (r = 0.437, p < 0.0001). The mean score for the early-career psychiatrists' confidence in their ability to diagnose and appropriately treat was notably low, at 3.13 ± 1.9.</p> <p>Conclusion</p> <p>Our results demonstrated that early-career psychiatrists self-evaluated their CAP clinical experience as insufficient, and these clinicians' CAP experiences and interests correlated significantly. Therefore, in order to improve child and adolescent medical care, we need to expose young psychiatrists to sufficient CAP cases and explore the factors that could attract them to this field.</p

Evolution of Proliferative Model Protocells Highly Responsive to the Environment

In this review, we discuss various methods of reproducing life dynamics using a constructive approach. An increase in the structural complexity of a model protocell is accompanied by an increase in the stage of reproduction of a compartment (giant vesicle; GV) from simple reproduction to linked reproduction with the replication of information molecules (DNA), and eventually to recursive proliferation of a model protocell. An encounter between a plural protic catalyst (C) and DNA within a GV membrane containing a plural cationic lipid (V) spontaneously forms a supramolecular catalyst (C@DNA) that catalyzes the production of cationic membrane lipid V. The local formation of V causes budding deformation of the GV and equivolume divisions. The length of the DNA strand influences the frequency of proliferation, associated with the emergence of a primitive information flow that induces phenotypic plasticity in response to environmental conditions. A predominant protocell appears from the competitive proliferation of protocells containing DNA with different strand lengths, leading to an evolvable model protocell. Recently, peptides of amino acid thioesters have been used to construct peptide droplets through liquid–liquid phase separation. These droplets grew, owing to the supply of nutrients, and were divided repeatedly under a physical stimulus. This proposed chemical system demonstrates a new perspective of the origins of membraneless protocells, i.e., the “droplet world” hypothesis. Proliferative model protocells can be regarded as autonomous supramolecular machines. This concept of this review may open new horizons of “evolution” for intelligent supramolecular machines and robotics

Physicochemical Cause and Effect Observed in DNA Length-Dependent Division of Protocell as the Primitive Flow of Information

In the prebiotic era, physicochemical cause and effect served as the primitive flow of information for protocells. Our recent study claimed that the manners and frequencies of self-reproduction of giant vesicle (GV) -based model protocells were regulated by the incorporated DNA-length, and not the base-pair sequence due to the presence of a supramolecular catalyst (lipo-deoxyribozyme) composed of DNA and lipophilic catalysts. The DNA-length dependent dynamics of the self-reproducing GVs containing different length of DNA were examined by three independent experiments; Population analysis by flow cytometric measurements, counting of　increased numbers of protocells and direct morphological observation of a single GV by confocal microscopy. These results may shed light on the information system in the prebiotic stage, when the central dogma was not established. Notably, recent reports have revealed the possible influence of DNA length on the activation of living cells through the complexation of DNA to an enzyme in non-sequential aggregation manner.This work was supported by JSPS KAKENHI (Grant Numbers JP25103009, JP16K05759 and JP17H04876), ‘Platform for Dynamic Approaches to Living System’ at the University of Tokyo, Kanagawa University Grant for Joint Research, and the Yoshida Scholarship Foundation

Parallel Computation of Rough Set Approximations in Information Systems with Missing Decision Data

The paper discusses the use of parallel computation to obtain rough set approximations from large-scale information systems where missing data exist in both condition and decision attributes. To date, many studies have focused on missing condition data, but very few have accounted for missing decision data, especially in enlarging datasets. One of the approaches for dealing with missing data in condition attributes is named twofold rough approximations. The paper aims to extend the approach to deal with missing data in the decision attribute. In addition, computing twofold rough approximations is very intensive, thus the approach is not suitable when input datasets are large. We propose parallel algorithms to compute twofold rough approximations in large-scale datasets. Our method is based on MapReduce, a distributed programming model for processing large-scale data. We introduce the original sequential algorithm first and then the parallel version is introduced. Comparison between the two approaches through experiments shows that our proposed parallel algorithms are suitable for and perform efficiently on large-scale datasets that have missing data in condition and decision attributes

Colocalization Analysis of Lipo-Deoxyribozyme Consisting of DNA and Protic Catalysts in a Vesicle-Based Protocellular Membrane Investigated by Confocal Microscopy

The linkage between the self-reproduction of compartments and the replication of DNA in a compartment is a crucial requirement for cellular life. In our giant vesicle (GV)-based model protocell, this linkage is achieved through the action of a supramolecular catalyst composed of membrane-intruded DNA and amphiphilic acid catalysts (C@DNA) in a GV membrane. In this study, we examined colocalization analysis for the formation of the supramolecular catalyst using a confocal laser scanning fluorescence microscope with high sensitivity and resolution. Red fluorescence spots emitted from DNA tagged with Texas Red (Texas Red-DNA) were observed in a GV membrane stained with phospholipid tagged with BODIPY (BODIPY-HPC). To our knowledge, this is the first direct observation of DNA embedded in a GV-based model protocellular membrane containing cationic lipids. Colocalization analysis based on a histogram of frequencies of &ldquo;normalized mean deviation product&rdquo; revealed that the frequencies of positively correlated [lipophilic catalyst tagged with BODIPY (BODIPY-C) and Texas Red-DNA] were significantly higher than those of [BODIPY-HPC and Texas Red-DNA]. This result demonstrates the spontaneous formation of C@DNA in the GV membrane, which serves as a lipo-deoxyribozyme for producing membrane lipids from its precursor