Intracellular processes of the white-rot basidiomycete Phanerochaete chrysosporium involved in the metabolism of benzoic acid (BA) were investigated at the proteome and metabolome level. ...Up-regulation of aryl-alcohol dehydrogenase, arylaldehyde dehydrogenase, and cytochrome P450s was observed upon addition of exogenous BA, suggesting that these enzymes play key roles in its metabolism. Intracellular metabolic shifts from the short-cut TCA/glyoxylate bicycle system to the TCA cycle and an increased flux in the TCA cycle indicated activation of the heme biosynthetic pathway and the production of NAD(P)H. In addition, combined analyses of proteome and metabolome clearly indicated the role of trehalose as a storage disaccharide and that the mannitol cycle plays a role in an alternative energy-producing pathway.
Neurons are highly polarized cells with long neurites. Vesicular transport is required for neurite extension. We recently identified protrudin as a key regulator of vesicular transport during neurite ...extension. Expression of protrudin in nonneuronal cells thus induces formation of neurite-like membrane protrusions. We adopted a proteomics approach to identify proteins that associate with protrudin. Among the protrudin-associated proteins, including many with a function related to intracellular trafficking, we focused on KIF5, a motor protein that mediates anterograde vesicular transport in neurons. A coimmunoprecipitation assay confirmed that endogenous protrudin and KIF5 interact in mouse brain. Overexpression of KIF5 induced the formation of membrane protrusions in HeLa cells, reminiscent of the effect of protrudin overexpression. Forced expression of both protrudin and KIF5 promoted protrusion extension in a synergistic manner, whereas depletion of either protein attenuated protrusion formation. Protrudin facilitated the interaction of KIF5 with Rab11, VAP-A and -B, Surf4, and RTN3, suggesting that protrudin serves as an adaptor protein and that the protrudin-KIF5 complex contributes to the transport of these proteins in neurons. Given that mutation of protrudin or KIF5 is a cause of human hereditary spastic paraplegia, the protrudin-KIF5 axis appears to be integral to neuronal function.
Protrudin is a membrane protein that regulates polarized vesicular trafficking in neurons. The protrudin gene (ZFYVE27) is mutated in a subset of individuals with hereditary spastic paraplegia (HSP), ...and protrudin is therefore also referred to as spastic paraplegia (SPG) 33. We have now generated mice that express a transgene for dual epitope-tagged protrudin under control of a neuron-specific promoter, and we have subjected highly purified protrudin-containing complexes isolated from the brain of these mice to proteomics analysis to identify proteins that associate with protrudin. Protrudin was found to interact with other HSP-related proteins including myelin proteolipid protein 1 (SPG2), atlastin-1 (SPG3A), REEP1 (SPG31), REEP5 (similar to REEP1), Kif5A (SPG10), Kif5B, Kif5C, and reticulon 1, 3, and 4 (similar to reticulon 2, SPG12). Membrane topology analysis indicated that one of three hydrophobic segments of protrudin forms a hydrophobic hairpin domain similar to those of other SPG proteins. Protrudin was found to localize predominantly to the tubular endoplasmic reticulum (ER), and forced expression of protrudin promoted the formation and stabilization of the tubular ER network. The protrudin(G191V) mutant, which has been identified in a subset of HSP patients, manifested an increased intracellular stability, and cells expressing this mutant showed an increased susceptibility to ER stress. Our results thus suggest that protrudin contributes to the regulation of ER morphology and function, and that its deregulation by mutation is a causative defect in HSP.
Certain hereditary spastic paraplegia (HSP)-related proteins possess hairpin domains and regulate the morphology of the endoplasmic reticulum (ER) network.
Protrudin possesses a hairpin domain and interacts with HSP-related proteins.
Protrudin regulates ER morphology and function.
Mutant protrudin produced in certain individuals with HSP is prone to form microaggregates that induce ER stress.
Purpose
To elucidate the status of medication use among pregnant women in Japan, by means of a multigenerational genome and birth cohort study: the Tohoku Medical Megabank Project Birth and ...Three-Generation Cohort Study (TMM BirThree Cohort Study).
Methods
Questionnaires were distributed to pregnant women participating in the TMM BirThree Cohort Study (from July 2013 to March 2017) around 12 weeks (early pregnancy) and 26 weeks (middle pregnancy). We analysed medication use over three periods: (1) 12 months prior to pregnancy diagnosis, (2) the period between pregnancy diagnosis and around week 12 of pregnancy, and (3) post around week 12 of pregnancy.
Results
In total, 19,297 women were included in the analysis. The proportion of pregnant women using medications was 49.0% prior to pregnancy diagnosis, 52.1% from diagnosis to week 12, and 58.4% post week 12 of pregnancy. The most frequently prescribed medications were loxoprofen sodium hydrate (5.5%) prior to pregnancy diagnosis, magnesium oxide (5.9%) from diagnosis to week 12, and ritodrine hydrochloride (10.5%) post week 12 of pregnancy. The number of women who used suspected teratogenic medications during early pregnancy was 96 prior to pregnancy diagnosis, 48 from diagnosis to week 12, and 54 post week 12 of pregnancy.
Conclusion
We found that ~ 50% of the pregnant women used medications before and during pregnancy and some took potential teratogenic medications during pregnancy. In birth genomic cohort study, it is expected that investigations into the safety and effectiveness of medications used during pregnancy will advance.
When using administrative data, validation is essential since these data are not collected for research purposes and misclassification can occur. Thus, this study aimed to develop algorithms ...identifying pregnancy and to evaluate the validity of administrative claims data in Japan.
All females who visited the Tohoku University Hospital Department of Obstetrics in 2018 were included. The diagnosis, medical procedure, medication, and medical service addition fee data were utilized to identify pregnancy, with the electronic medical records set as the gold standard. Combination algorithms were developed using predefined pregnancy-related claims data with a positive predictive value (PPV) ≥80%. Sensitivity (SE), specificity (SP), PPV, and negative predictive value (NPV) with their corresponding 95% confidence intervals (CIs) were calculated for these combination algorithms.
This study included 1757 females with a mean age of 32.8 (standard deviation: 5.9) years. In general, the individual claims data were able to identify pregnancy with a PPV ≥80%; however, the number of pregnancies identified using a single claims data was limited. Based on the combination algorithm with all of the categories, including diagnosis, medical procedure, medication, and medical service addition, the calculated SE, SP, PPV, and NPV were 73.4% (95% CI: 71.2%-75.4%), 96.9% (95% CI: 89.3%-99.6%), 99.8%,(95% CI: 99.4%-100.0%), and 12.3% (95% CI: 9.6%-15.4%), respectively.
The combination algorithm to identify pregnancy demonstrated a high PPV and moderate SE. The algorithm validated in this study is expected to accelerate future studies that aim to identify pregnancies and evaluate pregnancy outcome.
This study aimed to develop and validate claims-based algorithms for identifying live birth, fetal death, and cesarean section by utilizing administrative data from a university hospital in Japan. We ...included women who visited the Department of Obstetrics at a university hospital in 2018. The diagnosis, medical procedures, and medication data were used to identify potential cases of live birth, fetal death, and cesarean section. By reviewing electronic medical records, we evaluated the positive predictive values (PPVs) and the accuracy of the end date of pregnancy for each claims datum. "Selected algorithm 1" based on PPVs and "selected algorithm 2" based on both the PPVs and the accuracy of the end date of pregnancy were developed. A total of 1757 women were included, and the mean age was 32.8 years. The PPVs of "selected algorithm 1" and "selected algorithm 2" were both 98.1% for live birth, 99.0% and 98.9% for fetal death, and 99.7% and 100.0% for cesarean section, respectively. These findings suggest that the developed algorithms are useful for future studies for evaluating live birth, fetal death, and cesarean section with an accurate end date of pregnancy.
In a large-scale disaster, medical professionals need to access medication records and provide medicines to people who cannot return home to take their daily medicines. We investigated the proportion ...of carrying the paper notebook or availability of the smartphone application of the medication record among people who are assumed to have difficulty in taking their medicines during large-scale disasters.
In Japan, a web-based survey was conducted in 2018 by randomly selecting adults ≥ 20 years of age.
There were 2286 medication record owners in 3082 participants. Of the medication record owners, 784 (34.3%) took medicines that could not be missed for even a day. Among them, 724 used paper notebooks alone, 26 used smartphone applications alone, and 34 used both. Among the 724, 208 (28.8%) always carried a paper notebook. Among the 26, 16 (61.5%) could use their applications anytime. Therefore, among the 784, at least 560 (71.4%) could not always access their medication information.
An awareness campaign to carry paper notebooks and install applications for medication records should be held, since only a limited number of people carry their medication records and always have access to their medication information.
Aim
An association between maternal psychological distress and children's development has been reported, but reports from Japan are limited. This study aimed to examine the association of maternal ...psychological distress with children's neurodevelopment in Japan.
Methods
The study assessed data of 7646 mother–infant pairs in the Japanese population. We used Kessler Psychological Distress Scale, a screening tool for psychological distress, to assess maternal psychological distress in early pregnancy and 2 years postpartum and divided it into four categories: none in both the pre‐natal and post‐natal periods, only the pre‐natal period, only the post‐natal period and both the pre‐natal and post‐natal periods. Children's neurodevelopment was assessed using the Ages & Stages Questionnaires Third Edition (ASQ‐3) at 4 years of age. ASQ‐3 comprises five domains (communication, gross motor, fine motor, problem solving and personal–social), and the score of less than −2 standard deviation relative to the mean in reference was defined as having developmental delay. We conducted multivariate logistic regression analysis to examine the association between maternal psychological distress and children's neurodevelopment.
Results
The prevalence of developmental delay of communication, gross motor, fine motor, problem solving and personal–social were 4.0%, 4.3%, 4.9%, 3.8% and 4.6%, respectively. Maternal psychological distress in only the postpartum period and both pre‐natal and postpartum periods were associated with risks of developmental delay in all domains. Maternal psychological distress in only the pre‐natal period was associated with developmental delay in communication.
Conclusions
Maternal psychological distress is associated with risks of children's developmental delay.
AimAn association between maternal psychological distress and children's development has been reported, but reports from Japan are limited. This study aimed to examine the association of maternal ...psychological distress with children's neurodevelopment in Japan.MethodsThe study assessed data of 7646 mother–infant pairs in the Japanese population. We used Kessler Psychological Distress Scale, a screening tool for psychological distress, to assess maternal psychological distress in early pregnancy and 2 years postpartum and divided it into four categories: none in both the pre‐natal and post‐natal periods, only the pre‐natal period, only the post‐natal period and both the pre‐natal and post‐natal periods. Children's neurodevelopment was assessed using the Ages & Stages Questionnaires Third Edition (ASQ‐3) at 4 years of age. ASQ‐3 comprises five domains (communication, gross motor, fine motor, problem solving and personal–social), and the score of less than −2 standard deviation relative to the mean in reference was defined as having developmental delay. We conducted multivariate logistic regression analysis to examine the association between maternal psychological distress and children's neurodevelopment.ResultsThe prevalence of developmental delay of communication, gross motor, fine motor, problem solving and personal–social were 4.0%, 4.3%, 4.9%, 3.8% and 4.6%, respectively. Maternal psychological distress in only the postpartum period and both pre‐natal and postpartum periods were associated with risks of developmental delay in all domains. Maternal psychological distress in only the pre‐natal period was associated with developmental delay in communication.ConclusionsMaternal psychological distress is associated with risks of children's developmental delay.
In the ubiquitin-proteasome system, E3 ubiquitin ligase (E3s for short) selectively recognize and bind specific regions of their substrate proteins. Sequence motifs whose sites are bound by E3 ...ubiquitin ligases are called degrons. Because much remains unclear about the relationship between substrate proteins of E3s and their binding sites, there is a need to computationally identify such binding sites from the substrate proteins. For this motif identification problem, in our previous works, we have proposed a series of collapsed Gibbs sampling algorithms, called DegSampler1 and DegSampler2, both of which use position-specific prior information. In this work, we propose a new collapsed Gibbs sampling algorithm, called DegSampler3, by integrating intra-motif pair-wise dependency model into the posterior probability distribution of DegSampler2. In our preliminary experiments, we found that DegSampler3 has the ability of finding more various degron sites than DegSampler2 while keeping the prediction accuracy almost the same as that of the previous method, DegSampler2.
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