Categorization of Escherichia coli outer membrane proteins by dependence on accessory proteins of the ß-barrel assembly machinery complex.

The outer membrane (OM) of gram-negative bacteria is populated by various outer membrane proteins (OMPs) that fold into a unique ß-barrel transmembrane domain. Most OMPs are assembled into the OM by the ß-barrel assembly machinery (BAM) complex. In Escherichia coli, the BAM complex is composed of two essential proteins (BamA and BamD) and three nonessential accessory proteins (BamB, BamC, and BamE). The currently proposed molecular mechanisms of the BAM complex involve only essential subunits, with the function of the accessory proteins remaining largely unknown. Here, we compared the accessory protein requirements for the assembly of seven different OMPs, 8- to 22-stranded, by our in vitro reconstitution assay using an E. coli mid-density membrane. BamE was responsible for the full efficiency of the assembly of all tested OMPs, as it enhanced the stability of essential subunit binding. BamB increased the assembly efficiency of more than 16-stranded OMPs, whereas BamC was not required for the assembly of any tested OMPs. Our categorization of the requirements of BAM complex accessory proteins in the assembly of substrate OMPs enables us to identify potential targets for the development of new antibiotics.

Research trends on maxillary sinus septa in 2019-2021: a scoping review with scientometric analysis.

PURPOSE: This study aimed to conduct a bibliometric analysis of trends in the description items within the literature published from 2019 to 2021 with "maxillary sinus septum" in the title or subtitle. METHODS: Electronic data from PubMed (MEDLINE), Google Scholar, and ScienceDirect were searched from 2019 to 2021. We used the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) to select 21 of 243 articles and examined their studies. Statistical calculations from data recorded by the authors were performed using the Chi-square, Mann-Whitney, and independent tests. Significance was set at P < 0.05. RESULTS: The number of articles decreased annually. The highest number of publications was from Asia (64.3%), accounting for 71.4% of publications. The features of the septum were described for eight items, with one septum (70.14%) mentioned significantly more frequently, followed by on one side (65.89%) or the right side (62.22%). Location was mentioned significantly more frequently in the middle (55.22%) and for those aged 45 years and older (50.38%). No significant differences were observed in prevalence, age, height, or width between sexes; the patients' ages ranged from 18 to 90 years. Septa were significantly more prevalent in dentulous (45.38%) and partially edentulous (48.58%) patients, with significantly more patients exhibiting buccopalatal orientation (82.39%). CONCLUSIONS: This study focused primarily on anatomical features using CBCT examination, and analyses of male-female differences and the origin of the sinus septum are necessary for the future.

In Vivo Label-Free Observation of Tumor-Related Blood Vessels in Small Animals Using a Newly Designed Photoacoustic 3D Imaging System.

Photoacoustic (PA) technology can be used for non-invasive imaging of blood vessels. In this paper, we report on our prototype PA imaging system with a newly designed ultrasound sensor and its visualization performance of microvascular in animal. We fabricated an experimental system for animals using a high-frequency sensor. The system has two modes: still image mode by wide scanning and moving image mode by small rotation of sensor array. Optical test target, euthanized mice and rats, and live mice were used as objects. The results of optical test target showed that the spatial resolution was about two times higher than that of our conventional prototype. The image performance in vivo was evaluated in euthanized healthy mice and rats, allowing visualization of detailed blood vessels in the liver and kidneys. In tumor-bearing mice, different results of vascular induction were shown depending on the type of tumor and the method of transplantation. By utilizing the video imaging function, we were able to observe the movement of blood vessels around the tumor. We have demonstrated the feasibility of the system as a less invasive animal experimental device, as it can acquire vascular images in animals in a non-contrast and non-invasive manner.

Mast Cells Are Activated in the Giant Earlobe Keloids: A Case Series.

Mast cells and inflammatory cells are abundant in keloid and hypertrophic scar tissues. Even if the cause of physical injury is similar, such as piercing or scratching with hands, clinical findings show differences in the size of keloids in the same area. Hence, we performed histological studies on giant keloids larger than the earlobe, and other smaller keloids. We also examined the risk factors associated with the formation of giant lesions. No statistically significant differences in the association of the risk factors were observed. However, histological observations clearly showed a high number of degranulated or active mast cells with a trend towards a greater number of degranulated mast cells in the giant keloid tissues. Collagen production also tended to increase. Two patients with giant keloids were severely obese, suggesting that the persistent inflammatory state of obesity may also be involved in the growth of keloid lesions.

De Novo Mutations Activating Germline TP53 in an Inherited Bone-Marrow-Failure Syndrome.

Inherited bone-marrow-failure syndromes (IBMFSs) include heterogeneous genetic disorders characterized by bone-marrow failure, congenital anomalies, and an increased risk of malignancy. Many lines of evidence have suggested that p53 activation might be central to the pathogenesis of IBMFSs, including Diamond-Blackfan anemia (DBA) and dyskeratosis congenita (DC). However, the exact role of p53 activation in each clinical feature remains unknown. Here, we report unique de novo TP53 germline variants found in two individuals with an IBMFS accompanied by hypogammaglobulinemia, growth retardation, and microcephaly mimicking DBA and DC. TP53 is a tumor-suppressor gene most frequently mutated in human cancers, and occasional germline variants occur in Li-Fraumeni cancer-predisposition syndrome. Most of these mutations affect the core DNA-binding domain, leading to compromised transcriptional activities. In contrast, the variants found in the two individuals studied here caused the same truncation of the protein, resulting in the loss of 32 residues from the C-terminal domain (CTD). Unexpectedly, the p53 mutant had augmented transcriptional activities, an observation not previously described in humans. When we expressed this mutant in zebrafish and human-induced pluripotent stem cells, we observed impaired erythrocyte production. These findings together with close similarities to published knock-in mouse models of TP53 lacking the CTD demonstrate that the CTD-truncation mutations of TP53 cause IBMFS, providing important insights into the previously postulated connection between p53 and IBMFSs.

The Incidence of Sleep Disordered Breathing One Week After Primary Palatoplasty: Evaluation With Overnight Pulse Oximetry.

BACKGROUND: Sleep disordered breathing (SDB) is defined as a series of disorders including snoring, obstructive sleep apnea, and hypopnea. Few studies investigated the incidence of SDB following primary palatoplasty with objective testing. The aims of this study were to elucidate the prevalence and degree of SDB approximately 1 week following primary palatoplasty with objective testing and to clarify the risk factors. METHOD: A retrospective review was performed on children who underwent primary palatoplasty between April 2013 and July 2017 at National Center for Child Health and Development, Tokyo, Japan. As a national center, the authors accept many syndromic patients. The authors keep all patients after palatoplasty intubated and observe them overnight in intensive care unit to reduce the risks of respiratory events. Patients were evaluated with overnight pulse oximetry on 5 to 7 days postoperatively. RESULTS: Forty-four patients were included, and 30% of the patients were associated with congenital anomaly. Thirteen patients (30%) were diagnosed with SDB. None of the patients required additional treatment after the evaluation. Laryngomalacia and postoperative oxygen requirement significantly correlated with postoperative SDB. CONCLUSION: Approximately one-third of the patients may be at the risk of SDB 1 week after primary palatoplasty. Patients with history of laryngomalacia or those who required oxygen support for prolonged time after primary palatoplasty should be cared for significantly high risk of postoperative SDB.

Analysis of Cranial Morphology of Healthy Infants Using Homologous Modeling.

OBJECTIVE: Data on cranial morphology of healthy individuals can be used as the guide in the treatment of cranial deformity. There are many reports analyzing the cranial morphology of healthy children in the past. But most of them focus on 2-dimensional values, and there are only a few reports, which analyzed the cranial morphology of Japanese healthy infants. We report a novel method that enables the comprehensive analysis of cranial morphology of Japanese healthy infants in 3D. METHODS: Craniofacial CT data of 20 healthy infants (9 males, 11 females) ranging in age from 1 to 11 months were collected. Based on the CT data, we created 20 homologous models of cranium using software specifically designed to support homologous modeling. We averaged vertex coordinates of the homologous models to create average model. We further performed principal component analysis, and created virtual models based on each principal component. The contribution rate was calculated, and the features described by each principal component were interpreted. RESULTS: We created the average cranial model of Japanese healthy infants. Seven principal components (cumulative contribution rate: 89.218%) were interpreted as to which part of the cranial shape each component was related to. The elements were extracted that may characterize the cranial morphology of some of the clinical conditions such as dolico/brachycephaly and deformational plagiocephaly. Some of these elements have not been mentioned in the past literature. CONCLUSION: Homologous modeling was considered to be valid and strong tool for comprehensive analysis of cranial morphology.

Cross talk between TP53 and c-Myc in the pathophysiology of Diamond-Blackfan anemia: Evidence from RPL11-deficient in vivo and in vitro models.

Mutations in genes encoding ribosomal proteins have been identified in Diamond-Blackfan anemia (DBA), a rare genetic disorder that presents with a prominent erythroid phenotype. TP53 has been implicated in the pathophysiology of DBA with ribosomal protein (RP) L11 playing a crucial role in the TP53 response. Interestingly, RPL11 also controls the transcriptional activity of c-Myc, an oncoprotein that positively regulates ribosome biogenesis. In the present study, we analyzed the consequences of rpl11 depletion on erythropoiesis and ribosome biogenesis in zebrafish. As expected, Rpl11-deficient zebrafish exhibited defects in ribosome biogenesis and an anemia phenotype. However, co-inhibition of Tp53 did not alleviate the erythroid aplasia in these fish. Next, we explored the role of c-Myc in RPL11-deficient cellular and animal models. c-Myc and its target nucleolar proteins showed upregulation and increased localization in the head region of Rpl11-deficient zebrafish, where the morphological abnormalities and tp53 expression were more pronounced. Interestingly, in blood cells derived from DBA patients with mutations in RPL11, the biogenesis of ribosomes was defective, but the expression level of c-Myc and its target nucleolar proteins was unchanged. The results suggest a model whereby RPL11 deficiency activates the synthesis of c-Myc target nucleolar proteins, which subsequently triggers a p53 response. These results further demonstrate that the induction of Tp53 mediates the morphological, but not erythroid, defects associated with RPL11 deficiency.

Child restraint orientation: Accuracy of information on Japanese websites.

BACKGROUND: Child restraints provide maximum protection when used appropriately, but seat orientation (rear- or forward-facing) according to child development is often misunderstood, and the information provided can be inaccurate. This study examined the accuracy of information in Japanese on seat orientation found on the Internet. METHODS: We searched websites in Japanese on Google regarding information on recommended seat orientation for young children and examined the first 50 sites based on the search rankings for the criteria on when to allow children to ride in forward-facing seats. RESULTS: None of the examined websites included information that was consistent with the recommendation of the Japan Pediatric Society (i.e. age must be at least 1 year old and weight, at least 10 kg). The most common mistake was that weight alone could determine timing. CONCLUSIONS: More vigorous efforts are needed to disseminate evidence-based information about seat orientation to protect child passengers.

Effects of a Skin Barrier Cream on Management of Incontinence-Associated Dermatitis in Older Women: A Cluster Randomized Controlled Trial.

PURPOSE: The purpose of this study was to examine the effects of a skin barrier cream with moisturization and skin-protectant characteristics for improving the severity of incontinence-associated dermatitis (IAD) pertaining to the skin physiology and appearance. We measured the following outcomes: (1) skin physiological characteristics indicating skin protection and enhancement of the skin's moisture barrier (stratum corneum hydration, dermis hydration level, transepidermal water loss, and skin pH); and (2) changes in skin appearance (the degree of erythema and pigmentation, and the sulcus cutis condition). DESIGN: Single-blind, cluster randomized controlled trial. SUBJECTS AND SETTING: The study was conducted in a long-term care facility in Japan between November 7, 2011, and May 6, 2012. We used block randomization to obtain a random sample of 6 (4 experimental and 2 control) out of 10 available wards. All subjects were elderly women with IAD of the buttock or inner thigh. We assessed 295 patients, but only 33 met inclusion criteria; 18 were allocated to the experimental group and 15 were allocated to the control group. METHODS: All participants were managed with cleansing with a skin cleanser and application of a moisturizer daily. In addition, a skin barrier cream designed to enhance the skin's moisture barrier and act as a protective barrier was applied to the skin of patients in the experimental group 3 times a day when absorptive briefs were changed. Skin physiological and appearance characteristics were scored only at the buttock or thigh area. All data were collected on days 1 and 14 of the study. RESULTS: Univariate analysis found that the erythema index was lower in the intervention group than in the control group at day 14 (P = .004). Multivariate analysis found significant associations between use of the skin barrier cream and increased stratum corneum hydration (ß= .443, P = .031), decreased skin pH (ß=-.439, P = .020), and magnitude of erythema (ß=-.451, P = .018). CONCLUSIONS: Study findings suggest that a barrier cream designed to enhance the skin's moisture barrier and act as a skin protectant increased stratum corneum hydration, reduced cutaneous pH, and reduced erythema.

17ß-Estradiol administration promotes delayed cutaneous wound healing in 40-week ovariectomised female mice.

This study investigated the effect of 17ß-estradiol on wound healing in 40-week ovariectomised female mice. Thirty-six-week-old female mice were divided into three groups: medication with 17ß-estradiol after ovariectomy (OVX + 17ß-estradiol), ovariectomy (OVX) and sham (SHAM). The mice received two full-thickness wounds, and the OVX + 17ß-estradiol group was administered 17ß-estradiol at 0·01 g/day until healing. In the OVX + 17ß-estradiol group, the ratio of wound area was significantly smaller than those of the OVX and SHAM groups on days 1-3, 5, 6, 8-12 and 9-12, respectively, the numbers of neutrophils and macrophages were significantly smaller than those on days 3 and 7, the ratio of re-epithelialisation was significantly higher than those on days 3 and 11, the ratio of myofibroblasts was significantly higher than those on day 11 and smaller on day 14, and the ratio of collagen fibres was significantly larger than that of the OVX group on days 7-14. We found that 17ß-estradiol administration promotes cutaneous wound healing in 40-week female mice by reducing wound area, shortening inflammatory response, and promoting re-epithelialisation, collagen deposition and wound contraction. Our results suggest that cutaneous wound healing that is delayed because of ageing is promoted by exogenous and continuous 17ß-estradiol administration.

Plant Genome DataBase Japan (PGDBj): a portal website for the integration of plant genome-related databases.

The Plant Genome DataBase Japan (PGDBj, http://pgdbj.jp/?ln=en) is a portal website that aims to integrate plant genome-related information from databases (DBs) and the literature. The PGDBj is comprised of three component DBs and a cross-search engine, which provides a seamless search over the contents of the DBs. The three DBs are as follows. (i) The Ortholog DB, providing gene cluster information based on the amino acid sequence similarity. Over 500,000 amino acid sequences of 20 Viridiplantae species were subjected to reciprocal BLAST searches and clustered. Sequences from plant genome DBs (e.g. TAIR10 and RAP-DB) were also included in the cluster with a direct link to the original DB. (ii) The Plant Resource DB, integrating the SABRE DB, which provides cDNA and genome sequence resources accumulated and maintained in the RIKEN BioResource Center and National BioResource Projects. (iii) The DNA Marker DB, providing manually or automatically curated information of DNA markers, quantitative trait loci and related linkage maps, from the literature and external DBs. As the PGDBj targets various plant species, including model plants, algae, and crops important as food, fodder and biofuel, researchers in the field of basic biology as well as a wide range of agronomic fields are encouraged to perform searches using DNA sequences, gene names, traits and phenotypes of interest. The PGDBj will return the search results from the component DBs and various types of linked external DBs.

Loss of ribosomal RNA modification causes developmental defects in zebrafish.

Non-coding RNAs (ncRNAs) play key roles in diverse cellular activities, and efficient ncRNA function requires extensive posttranscriptional nucleotide modifications. Small nucleolar RNAs (snoRNAs) are a group of ncRNAs that guide the modification of specific nucleotides in ribosomal RNAs (rRNAs) and small nuclear RNAs. To investigate the physiological relevance of rRNA modification in vertebrates, we suppressed the expression of three snoRNAs (U26, U44 and U78), either by disrupting the host gene splicing or by inhibiting the snoRNA precursor processing, and analyzed the consequences of snoRNA loss-of-function in zebrafish. Using a highly sensitive mass spectrometric analysis, we found that decreased snoRNA expression reduces the snoRNA-guided methylation of the target nucleotides. Impaired rRNA modification, even at a single site, led to severe morphological defects and embryonic lethality in zebrafish, which suggests that rRNA modifications play an essential role in vertebrate development. This study highlights the importance of posttranscriptional modifications and their role in ncRNA function in higher eukaryotes.

Using an extreme bony prominence anatomical model to examine the influence of bed sheet materials and bed making methods on the distribution of pressure on the support surface.

Bed sheets generate high surface tension across the support surface and increase pressure to the body through a process known as the hammock effect. Using an anatomical model and a loading device characterized by extreme bony prominences, the present study compared pressure distributions on support surfaces across different bed making methods and bed sheet materials to determine the factors that influence pressure distribution. The model was placed on a pressure mapping system (CONFORMat; NITTA Corp., Osaka, Japan), and interface pressure was measured. Bed sheet elasticity and friction between the support surface and the bed sheets were also measured. For maximum interface pressure, the relative values of the following methods were higher than those of the control method, which did not use any bed sheets: cotton sheets with hospital corners (1.28, p = 0.02), polyester with no corners (1.29, p = 0.01), cotton with no corners (1.31, p = 0.003), and fitted polyester sheets (1.35, p = 0.002). Stepwise multiple regression analysis indicated that maximum interface pressure was negatively correlated with bed sheet elasticity (R(2) = 0.74). A statistically significant negative correlation was observed between maximum interface pressure and immersion depth, which was measured using the loading device (r = -0.40 and p = 0.04). We found that several combinations of bed making methods and bed sheet materials induced maximum interface pressures greater than those observed for the control method. Bed sheet materials influenced maximum interface pressure, and bed sheet elasticity was particularly important in reducing maximum interface pressure.

Factors Related to Satisfaction with Decision-making Regarding Human Papillomavirus Vaccination Behavior among Female University Students in Japan.

Introduction: Cervical cancer is the fourth most common cancer among women worldwide. Most cervical cancers are caused by persistent infection with human papillomavirus (HPV) acquired through sexual contact. Decision-making is the process of choosing among several options, and a better decision is one that the people engaged in the decision-making process express satisfaction with. Despite that HPV infection is associated with sexual behavior, no studies in Japan on HPV vaccination decision-making that include perspectives on sexuality exist. This study aimed to determine the factors that influence satisfaction with decision-making concerning HPV vaccination among female university students in Japan. Methods: The cross-sectional study was carried out by an anonymous self-administered questionnaire mail survey of 1988 female university students in Japan between April and July 2021. Of them, 301 agreed to participate in the survey. After the exclusion of those with missing data, the analysis included 252 (12.7%) students. We summarized descriptive statistics in terms of characteristics, satisfaction with decision-making regarding HPV vaccination, HPV vaccination behavior, knowledge, attitude about HPV vaccination, influencing factors, and perceptions and behaviors related to sexuality. Furthermore, we conducted multivariate analyses to investigate factors that influence satisfaction with decision-making regarding HPV vaccination. Results: Of the 252 participants, 102 (40.5%) were satisfied with their decisions regarding HPV vaccination. After adjustment for confounding factors, the multivariable-adjusted odds ratios (95% confidence intervals) for factors associated with satisfaction in decision-making regarding HPV vaccination were as follows: being vaccinated (vs. non-vaccinated) 5.46 (2.51-11.89), having high knowledge scores (vs. per 1 point) 1.09 (1.01-1.17), and having awareness about the risk of contracting sexually transmitted infections (STIs) via sexual intercourse (vs. per 1 point) 0.83 (0.72-0.96). Conclusions: Being vaccinated, having higher knowledge scores, and having lower awareness regarding the risk of STIs were associated with satisfied decision-making concerning HPV vaccination. Providing younger people with correct information about cervical cancer, HPV vaccines, and STI prevention contributes to increased satisfaction with their HPV vaccination decisions.

Dual recognition of multiple signals in bacterial outer membrane proteins enhances assembly and maintains membrane integrity.

Outer membrane proteins (OMPs) are essential components of the outer membrane of Gram-negative bacteria. In terms of protein targeting and assembly, the current dogma holds that a 'ß-signal' imprinted in the final ß-strand of the OMP engages the ß-barrel assembly machinery (BAM) complex to initiate membrane insertion and assembly of the OMP into the outer membrane. Here, we revealed an additional rule that signals equivalent to the ß-signal are repeated in other, internal ß-strands within bacterial OMPs, by peptidomimetic and mutational analysis. The internal signal is needed to promote the efficiency of the assembly reaction of these OMPs. BamD, an essential subunit of the BAM complex, recognizes the internal signal and the ß-signal, arranging several ß-strands and partial folding for rapid OMP assembly. The internal signal-BamD ordering system is not essential for bacterial viability but is necessary to retain the integrity of the outer membrane against antibiotics and other environmental insults.

Regeneration of Panniculus Carnosus Muscle in Fetal Mice Is Characterized by the Presence of Actin Cables.

Mammalian skin, including human and mouse skin, does not regenerate completely after injury; it is repaired, leaving a scar. However, it is known that skin wounds up to a certain stage of embryonic development can regenerate. The mechanism behind the transition from regeneration to scar formation is not fully understood. Panniculus carnosus muscle (PCM) is present beneath the dermal fat layer and is a very important tissue for wound contraction. In rodents, PCM is present throughout the body. In humans, on the other hand, it disappears and becomes a shallow fascia on the trunk. Fetal cutaneous wounds, including PCM made until embryonic day 13 (E13), regenerate completely, but not beyond E14. We visualized the previously uncharacterized development of PCM in the fetus and investigated the temporal and spatial changes in PCM at different developmental stages, ranging from full regeneration to non-regeneration. Furthermore, we report that E13 epidermal closure occurs through actin cables, which are bundles of actomyosin formed at wound margins. The wound healing process of PCM suggests that actin cables may also be associated with PCM. Our findings reveal that PCM regenerates through a similar mechanism.

Topical estrogen application promotes cutaneous wound healing in db/db female mice with type 2 diabetes.

Female sex hormones are beneficial effects for wound healing. However, till date, whether topical estrogen application can promote cutaneous wound healing in diabetes remains unclear. Therefore, the present study aimed to validate the effect of topical estrogen application on cutaneous wound healing in a type 2 diabetes db/db mice model. In total, 22 db/db female mice with type 2 diabetes and eight C57BL/6J female mice were subjected to two full-thickness wound injuries. The mice were divided into the db/db, db/db + estrogen, db/db + vehicle, and wild type (WT) groups. Wound healing was assessed until day 14. The db/db group had a significantly high wound area ratio (wound area/initial wound area) on days 3-14 and a significantly low re-epithelialization ratio on days 7 and 14. Moreover, their angiogenesis ratio was significantly low on day 7 and high on day 14. In contrast, compared with the db/db group, the db/db + estrogen group had a significantly lower wound area ratio on days 1-14 and angiogenesis ratio on day 14, thereby indicating early withdrawal of new blood vessels, as well as a significantly higher re-epithelialization ratio on days 7 and 14 and Ym1+ M2 macrophage/macrophage ratio on day 7. Moreover, microarray analysis showed that the top 10 upregulated or downregulated genes in the db/db group were reversed by estrogen treatment, particularly on day 14, in comparison with the WT group. Thus, topical estrogen application reduced the wound area, promoted re-epithelialization and angiogenesis, and increased the number of M2 macrophages in mice with type 2 diabetes. Furthermore, it improved the differential regulation of genes in db/db mice. Therefore, such treatment can enhance cutaneous wound healing in female mice with type 2 diabetes.

Secondary arteriovenous malformation due to subclavian vein occlusion.

An 80-year-old man underwent rectal resection and insertion of a central venous catheter through the left subclavian vein 16 years earlier. Following surgery, he developed edema of his left upper limb that became exacerbated and infected. Computed tomography showed occlusion of the subclavian vein and multiple arteriovenous shunts from the branches of the axillary artery to the venous sac of the axillary vein. Angiography confirmed numerous shunts between the branches of the axillary artery and vein and dilated collateral veins. Embolization of the venous sac was performed using coils, alcohol, and glue. Postprocedural angiography showed complete eradication of the nidus.