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BackgroundIt is well known that maternal diet affects the development of offspring. Herein, the relationship between maternal intake of fermented foods during pregnancy and offspring development was investigated.MethodsThe diet of 103,060 pregnant women at >4 months of gestation who were enrolled in the Japan Environment and Children's Study was analyzed. Their intake levels of fermented soybeans (miso and natto), yogurt, and cheese were investigated. The developmental status of the offspring at 3 years of age was assessed using the Ages and Stages Questionnaires (ASQ-3). Multivariable logistic regression analysis was performed to determine the risk of maternal intake levels of the fermented foods associated with subsequent developmental delay in the offspring.ResultsIntake of cheese was associated with a reduced risk of child developmental delay in all intake level groups from the second quartile onward. Intakes of miso and yogurt were associated with a reduced risk of developmental delay in communication skills in the fourth quartile. There was no association between intake of natto and developmental delay.ConclusionMaternal consumption of fermented foods during pregnancy may reduce the risk of later developmental delay in offspring. It is therefore important to review the mother's diet for fermented foods during pregnancy. However, further studies are warranted to evaluate the factors influencing the association between diet and offspring development.

Cigarette smoke has been recognized as a major risk factor for cardiovascular disease. However, its direct effects on rodent and human cardiomyocytes and its cellular mechanisms are not fully understood. In this study, we examined the direct effects of cigarette smoke extract (CSE) on contractile functions, intracellular Ca2+ dynamics, and mitochondrial function using cultured or freshly isolated rat ventricular myocytes and human induced pluripotent stem cell (iPS)-derived cardiomyocytes. In rat cardiomyocytes, CSE (≥0.1%) resulted in a time- and concentration-dependent cessation of spontaneous beating of cultured cardiomyocytes, eventually leading to cell death, which indicates direct toxicity. In addition, 1% CSE reduced contractile function of freshly isolated ventricular myocytes. Similar contractile dysfunction (declined spontaneous beating rate and contractility) was also observed in human iPS-derived cardiomyocytes. Regarding intracellular Ca2+ dynamics, 1% CSE increased the Ca2+ transient amplitude by greatly increasing systolic Ca2+ levels and slightly increasing diastolic Ca2+ levels. CSE also accelerated the decay of Ca2+ transients, and triggered spike-shaped Ca2+ transients in some cells. These results indicate that CSE causes abnormal Ca2+ dynamics in cardiomyocytes. Furthermore, CSE induced a cascade of mitochondrial dysfunctions, including increased mitochondrial reactive oxygen species, opening of mitochondrial permeability transition pore, reduction of mitochondrial membrane potential, and release of cytochrome c from mitochondria. These results suggest that CSE-induced contractile dysfunction and myocardial cell death is caused by abnormal Ca2+ dynamics and subsequent mitochondrial dysregulation, which would result in reduced bioenergetics and activation of cell death pathways.

The spinal dorsal horn comprises heterogeneous neuronal populations, that interconnect with one another to form neural circuits modulating various types of sensory information. Decades of evidence has revealed that transcription factors expressed in each neuronal progenitor subclass play pivotal roles in the cell fate specification of spinal dorsal horn neurons. However, the development of subtypes of these neurons is not fully understood in more detail as yet and warrants the investigation of additional transcription factors. In the present study, we examined the involvement of the POU domain-containing transcription factor Brn3a in the development of spinal dorsal horn neurons. Analyses of Brn3a expression in the developing spinal dorsal horn neurons in mice demonstrated that the majority of the Brn3a-lineage neurons ceased Brn3a expression during embryonic stages (Brn3a-transient neurons), whereas a limited population of them continued to express Brn3a at high levels after E18.5 (Brn3a-persistent neurons). Loss of Brn3a disrupted the localization pattern of Brn3a-persistent neurons, indicating a critical role of this transcription factor in the development of these neurons. In contrast, Brn3a overexpression in Brn3a-transient neurons directed their localization in a manner similar to that in Brn3a-persistent neurons. Moreover, Brn3a-overexpressing neurons exhibited increased axonal extension to the ventral and ventrolateral funiculi, where the axonal tracts of Brn3a-persistent neurons reside. These results suggest that Brn3a controls the soma localization and axonal extension patterns of Brn3a-persistent spinal dorsal horn neurons.

BLEG-1 from Bacillus lehensis G1 is an evolutionary divergent B3 metallo-β-lactamase (MBL) that exhibited both β-lactamase and glyoxalase II (GLXII) activities. Sequence, phylogeny, biochemical and structural relatedness of BLEG-1 to B3 MBL and GLXII suggested BLEG-1 might be an intermediate in the evolutionary path of B3 MBL from GLXII. The unique active site cavity of BLEG-1 that recognizes both β-lactam antibiotics and S-D-lactoylglutathione (SLG) had been postulated as the key factor for its dual activity. In this study, dynamic ensembles of BLEG-1 and its substrate complexes divulged conformational plasticity and binding modes of structurally distinct substrates to the enzyme, providing better insights into its structure-to-function relationship and enzymatic promiscuity. Our results highlight the flexible nature of the active site pocket of BLEG-1, which is governed by concerted loop motions involving loop7+α3+loop8 and loop12 around the catalytic core, thereby moulding the binding pocket and facilitate interactions of BLEG-1 with both ampicillin and SLG. The distribution of (i) predominantly hydrophobic amino acids in the N-terminal domain, and (ii) flexible amino acids with polar and/or charged side chains in both N- and C-termini provide additional advantages to BLEG-1 in confining the aromatic group of ampicillin, and polar groups of SLG, respectively. The importance of these residues for substrates binding was further confirmed by the reduction in MBL and GLXII activities upon alanine substitutions of Ile-10, Phe-57, Arg-94, Leu-95, and Arg-159. Based on molecular dynamics simulation, mutational, and biochemical data presented herein, the catalytic mechanisms of BLEG-1 toward the hydrolysis of β-lactams and SLG were proposed.

Chronic obstructive pulmonary disease (COPD) causes sarcopenia and osteoporosis. However, the mechanisms underlying muscle and bone loss as well as the interactions between muscle and bone in the COPD state remain unclear. Therefore, we herein investigated the effects of the COPD state on muscle and bone in mice intratracheally administered porcine pancreatic elastase (PPE). The intratracheal administration of PPE to mice significantly reduced trabecular bone mineral density (BMD), trabecular bone volume, trabecular number, cortical BMD and cortical area. It also significantly decreased grip strength, but did not affect muscle mass or the expression of myogenic differentiation-, protein degradation- or autophagy-related genes in the soleus and gastrocnemius muscles. Among the myokines examined, myostatin mRNA levels in the soleus muscles were significantly elevated in mice treated with PPE, and negatively related to grip strength, but not bone parameters, in mice treated with or without 2 U PPE in simple regression analyses. Grip strength positively related to bone parameters in mice treated with or without PPE. In conclusion, we showed that a PPE model of COPD in mice exerts dominant effects on bone rather than skeletal muscles. Increased myostatin expression in the soleus muscles of mice in the COPD state may negatively relate to a reduction in grip strength, but not bone loss.

The ability to perform an unrehearsed piece of music, or sight-read, is a skill required by music performers. In sight-reading, the performer reads and plays the music simultaneously, which requires the coordination of visual, auditory, and motor processing. While performing, they display a characteristic called eye-hand span, in which the part of the score being looked at precedes the part being played. They must recognize, decipher, and process the score in the time between reading a note and playing it. An individual's executive function (EF) that control their cognition, emotions, and behavior may be involved in overseeing these individual movements. However, no study has investigated how EF is related to the eye-hand span and performance during sight-reading. Therefore, the purpose of this study is to clarify the relationships among EF, eye-hand span, and piano performance. Thirty-nine Japanese pianists and college students aspiring to be pianists with an average of 33.3 years of experience participated in this study. They performed sight-reading of two types of music scores with different difficulty levels while their eye movements were measured using an eye tracker to obtain their eye-hand span. The core EFs of inhibition, working memory, and shifting, were measured directly for each participant. Piano performance was evaluated by two pianists who did not participate in the study. Structural equation modeling was used to analyze the results. The results showed that auditory working memory predicted eye-hand span (β = .73, p < .001 in easy score; β = .65, p < .001 in difficult score), and eye-hand span predicted performance (β = .57, p < .001 in easy score; β = .56, p < .001 in difficult score). Auditory working memory did not directly affect performance, but through eye-hand span. The eye-hand span for easy scores was significantly greater than that for difficult scores. Furthermore, in a difficult music score, the shifting ability predicted higher piano performance. These suggest that the input of notes from the eyes becomes sound in the brain and activates the auditory working memory, which is then transmitted to finger movement, resulting in piano performance. In addition, it was suggested that shifting ability is also needed to perform difficult scores.

BackgroundA primary colorectal cancer (CRC) tumor can contain heterogeneous cancer cells. As clones of cells with different properties metastasize to lymph nodes (LNs), they could show different morphologies. Cancer histologies in LNs of CRC remains to be described.MethodsOur study enrolled 318 consecutive patients with CRC who underwent primary tumor resection with lymph node dissection between January 2011 and June 2016. 119 (37.4%) patients who had metastatic LNs (mLNs) were finally included in this study. Cancer histologies in LNs were classified and compared with pathologically diagnosed differentiation in the primary lesion. The association between histologies in lymph node metastasis (LNM) and prognosis in patients with CRC was investigated.ResultsThe histologies of the cancer cells in the mLNs were classified into four types: tubular, cribriform, poorly differentiated, and mucinous. Same degree of pathologically diagnosed differentiation in the primary tumor produced various histological types in LNM. In Kaplan-Meier analysis, prognosis was worse in CRC patients with moderately differentiated adenocarcinoma who had at least some mLN also showing cribriform carcinoma than for those whose mLNs all showed tubular carcinoma.ConclusionsHistology in LNM from CRC might indicate the heterogeneity and malignant phenotype of the disease.

Mouse spermatogenesis, from spermatogonial stem cell proliferation to sperm formation, can be reproduced in vitro by culturing testis tissue masses of neonatal mice. However, it remains to be determined whether this method is also applicable when testis tissues are further divided into tiny fragments, such as segments of the seminiferous tubule (ST), a minimal anatomical unit for spermatogenesis. In this study, we investigated this issue using the testis of an Acrosin-GFP/Histone H3.3-mCherry (Acr/H3) double-transgenic mouse and monitored the expression of GFP and mCherry as indicators of spermatogenic progression. Initially, we noticed that the cut and isolated stretches of ST shrunk rapidly and conglomerated. We therefore maintained the isolation of STs in two ways: segmental isolation without truncation or embedding in soft agarose. In both cases, GFP expression was observed by fluorescence microscopy. By whole-mount immunochemical staining, meiotic spermatocytes and round and elongating spermatids were identified as Sycp3-, crescent-form GFP-, and mCherry-positive cells, respectively. Although the efficiency was significantly lower than that with tissue mass culture, we clearly showed that spermatogenesis can be induced up to the elongating spermatid stage even when the STs were cut into short segments and cultured in isolation. In addition, we demonstrated that lowered oxygen tension was favorable for spermatogenesis both for meiotic progression and for producing elongating spermatids in isolated STs. Culturing isolated STs rather than tissue masses is advantageous for explicitly assessing the various environmental parameters that influence the progression of spermatogenesis.

Social isolation and fragmentation represent global challenges, with the former stemming from a lack of interaction and the latter from exclusive mobs—both rooted in communication issues. Addressing these challenges, the philosophical realm introduces the concept of the "mixbiotic society." In this framework, individuals with diverse freedoms and values mix together in physical proximity with diverse mingling, recognizing their respective "fundamental incapacities" and uniting in solidarity. This study aims to provide novel measures to balance freedom and solidarity, specifically the intermediate between isolation and mobbing, within a mixbiotic society. To achieve this, we introduce simplified measures to evaluate dynamic communication patterns. These measures complement traditional social network analysis of static structures and conventional entropy-based assessments of dynamic patterns. Our specific hypothesis posits that the measures corresponding to four distinct phases are established by representing communication patterns as multidimensional vectors. These measures include the mean of Euclidean distance to quantify "mobism" for fragmentation, the relative distance change for "atomism" indicating isolation, and a composite measure derived from multiplying the mean and variance of cosine similarity for "mixism," reflecting the well-going state of a mixbiotic society. Additionally, nearly negligible measures correspond to "nihilism." Through the evaluation of seven real-society datasets (high school, primary school, workplace, village, conference, online community, and email), we demonstrate the utility of the "mixism" measure in assessing freedom and solidarity in society. These measures can be employed to typify communities on a radar chart and a communication trajectory graph. The superiority of the measures lies in their ability to evaluate dynamic patterns, ease of calculation, and easily interpretable meanings compared to conventional analyses. As a future development, alongside additional validation using diverse datasets, the mixbiotic society measures will be employed to analyze social issues and applied in the fields of digital democracy and platform cooperativism. [ABSTRACT FROM AUTHOR]

With the nationwide emphasis on improving outcomes for STEM undergraduates, it is important that we not only focus on modifying classroom instruction, but also provide students with the tools to maximize their independent learning time. There has been considerable work in laboratory settings examining two beneficial practices for enhancing learning: spacing and self-testing. In the current study, we examine biology students' study practices, particularly in the context of these two behaviors. We specifically investigate whether a light-touch study skills intervention focused on encouraging spacing and self-testing practices impacted their utilization. Based on pre- and post-course surveys, we found that students report utilizing both beneficial and ineffective study practices and confirm that usage of spacing and self-testing correlates with a higher course grade. We also found that students in the section of the course which received the study skills intervention were more likely to report continued use or adoption of spacing and self-testing compared to students in control sections without the intervention. Surprisingly, we found that underrepresented minorities (URMs) under-utilize self-testing, and that our intervention helped to partially ameliorate this gap. Additionally, we found that URMs who reported self-testing earned similar course grades compared to non-URMs who also self-tested, but that there was a much larger drop in performance for URMs who did not self-test relative to non-URMs who also did not self-test. Overall, we would encourage instructors to dedicate class time towards discussing the merits of beneficial study practices, especially for students that have historically underperformed in STEM disciplines.

Background: It is well known that maternal diet affects the development of offspring. Herein, the relationship between maternal intake of fermented foods during pregnancy and offspring development was investigated. Methods: The diet of 103,060 pregnant women at >4 months of gestation who were enrolled in the Japan Environment and Children's Study was analyzed. Their intake levels of fermented soybeans (miso and natto), yogurt, and cheese were investigated. The developmental status of the offspring at 3 years of age was assessed using the Ages and Stages Questionnaires (ASQ-3). Multivariable logistic regression analysis was performed to determine the risk of maternal intake levels of the fermented foods associated with subsequent developmental delay in the offspring. Results: Intake of cheese was associated with a reduced risk of child developmental delay in all intake level groups from the second quartile onward. Intakes of miso and yogurt were associated with a reduced risk of developmental delay in communication skills in the fourth quartile. There was no association between intake of natto and developmental delay. Conclusion: Maternal consumption of fermented foods during pregnancy may reduce the risk of later developmental delay in offspring. It is therefore important to review the mother's diet for fermented foods during pregnancy. However, further studies are warranted to evaluate the factors influencing the association between diet and offspring development. [ABSTRACT FROM AUTHOR]

Purpose: To clarify the morphological factors of the pelvis in patients with developmental dysplasia of the hip (DDH), three-dimensional (3D) pelvic morphology was analyzed using a template-fitting technique. Methods: Three-dimensional pelvic data of 50 patients with DDH (DDH group) and 3D pelvic data of 50 patients without obvious pelvic deformity (Normal group) were used. All patients were female. A template model was created by averaging the normal pelvises into a symmetrical and isotropic mesh. Next, 100 homologous models were generated by fitting the pelvic data of each group of patients to the template model. Principal component analysis was performed on the coordinates of each vertex (15,235 vertices) of the pelvic homologous model. In addition, a receiver-operating characteristic (ROC) curve was calculated from the sensitivity of DDH positivity for each principal component, and principal components for which the area under the curve was significantly large were extracted (p<0.05). Finally, which components of the pelvic morphology frequently seen in DDH patients are related to these extracted principal components was evaluated. Results: The first, third, and sixth principal components showed significantly larger areas under the ROC curves. The morphology indicated by the first principal component was associated with a decrease in coxal inclination in both the coronal and horizontal planes. The third principal component was related to the sacral inclination in the sagittal plane. The sixth principal component was associated with narrowing of the superior part of the pelvis. Conclusion: The most important factor in the difference between normal and DDH pelvises was the change in the coxal angle in both the coronal and horizontal planes. That is, in the anterior and superior views, the normal pelvis is a triangle, whereas in DDH, it was more like a quadrilateral. [ABSTRACT FROM AUTHOR]

BackgroundRapid deterioration of oxygenation occurs in novel coronavirus disease 2019 (COVID-19), and prediction of mechanical ventilation (MV) is needed for allocation of patients to intensive care unit. Since intubation is usually decided based on varying clinical conditions, such as required oxygen changes, we aimed to elucidate thresholds of increase in oxygen demand to predict MV use within 12 h.MethodsA single-center retrospective cohort study using data between January 2020 and January 2021was conducted. Data were retrieved from the hospital data warehouse. Adult patients diagnosed with COVID-19 with a positive polymerase chain reaction (PCR) who needed oxygen during admission were included. Hourly increments in oxygen demand were calculated using two consecutive oxygen values. Covariates were selected from measurements at the closest time points of oxygen data. Prediction of MV use within 12 h by required oxygen changes was evaluated with the area under the receiver operating curves (AUCs). A threshold for increased MV use risk was obtained from restricted cubic spline curves.ResultsAmong 66 eligible patients, 1835 oxygen data were analyzed. The AUC was 0.756 for predicting MV by oxygen demand changes, 0.888 by both amounts and changes in oxygen, and 0.933 by the model adjusted with respiratory rate, PCR quantification cycle (Ct), and days from PCR. The threshold of increments of required oxygen was identified as 0.44 L/min/h and the probability of MV use linearly increased afterward. In subgroup analyses, the threshold was lower (0.25 L/min/h) when tachypnea or frequent respiratory distress existed, whereas it was higher (1.00 L/min/h) when viral load is low (Ct ≥20 or days from PCR >7 days).ConclusionsHourly changes in oxygen demand predicted MV use within 12 h, with a threshold of 0.44 L/min/h. This threshold was lower with an unstable respiratory condition and higher with a low viral load.

Approximately 10-15% of individuals infected with Helicobacter pylori will develop ulcer disease (gastric or duodenal ulcer), while most people infected with H. pylori will be asymptomatic. The majority of infected individuals remain asymptomatic partly due to the inhibition of synthesis of cholesteryl α-glucosides in H. pylori cell wall by α1,4-GlcNAc-capped mucin O-glycans, which are expressed in the deeper portion of gastric mucosa. However, it has not been determined how cholesteryl α-glucosyltransferase (αCgT), which forms cholesteryl α-glucosides, functions in the pathogenesis of H. pylori infection. Here, we show that the activity of αCgT from H. pylori clinical isolates is highly correlated with the degree of gastric atrophy. We investigated the role of cholesteryl α-glucosides in various aspects of the immune response. Phagocytosis and activation of dendritic cells were observed at similar degrees in the presence of wild-type H. pylori or variants harboring mutant forms of αCgT showing a range of enzymatic activity. However, cholesteryl α-glucosides were recognized by invariant natural killer T (iNKT) cells, eliciting an immune response in vitro and in vivo. Following inoculation of H. pylori harboring highly active αCgT into iNKT cell-deficient (Jα18(-/-)) or wild-type mice, bacterial recovery significantly increased in Jα18(-/-) compared to wild-type mice. Moreover, cytokine production characteristic of Th1 and Th2 cells dramatically decreased in Jα18(-/-) compared to wild-type mice. These findings demonstrate that cholesteryl α-glucosides play critical roles in H. pylori-mediated gastric inflammation and precancerous atrophic gastritis.

Cell motility is related to the higher-order structure of chromatin. Stimuli that induce cell migration change chromatin organization; such stimuli include elevated histone H3 lysine 9 trimethylation (H3K9me3). We previously showed that depletion of histone H3 lysine 9 methyltransferase, SUV39H1, suppresses directional cell migration. However, the molecular mechanism underlying this association between chromatin and cell migration remains elusive. The Golgi apparatus is a cell organelle essential for cell motility. In this study, we show that loss of H3K9 methyltransferase SUV39H1 but not SETDB1 or SETDB2 causes dispersion of the Golgi apparatus throughout the cytoplasm. The Golgi dispersion triggered by SUV39H1 depletion is independent of transcription, centrosomes, and microtubule organization, but is suppressed by depletion of any of the following three proteins: LINC complex components SUN2, nesprin-2, or microtubule plus-end-directed kinesin-like protein KIF20A. In addition, SUN2 is closely localized to H3K9me3, and SUV39H1 affects the mobility of SUN2 in the nuclear envelope. Further, inhibition of cell motility caused by SUV39H1 depletion is restored by suppression of SUN2, nesprin-2, or KIF20A. In summary, these results show the functional association between chromatin organization and cell motility via the Golgi organization regulated by the LINC complex. [ABSTRACT FROM AUTHOR]

Chronic obstructive pulmonary disease (COPD) causes sarcopenia and osteoporosis. However, the mechanisms underlying muscle and bone loss as well as the interactions between muscle and bone in the COPD state remain unclear. Therefore, we herein investigated the effects of the COPD state on muscle and bone in mice intratracheally administered porcine pancreatic elastase (PPE). The intratracheal administration of PPE to mice significantly reduced trabecular bone mineral density (BMD), trabecular bone volume, trabecular number, cortical BMD and cortical area. It also significantly decreased grip strength, but did not affect muscle mass or the expression of myogenic differentiation-, protein degradation- or autophagy-related genes in the soleus and gastrocnemius muscles. Among the myokines examined, myostatin mRNA levels in the soleus muscles were significantly elevated in mice treated with PPE, and negatively related to grip strength, but not bone parameters, in mice treated with or without 2 U PPE in simple regression analyses. Grip strength positively related to bone parameters in mice treated with or without PPE. In conclusion, we showed that a PPE model of COPD in mice exerts dominant effects on bone rather than skeletal muscles. Increased myostatin expression in the soleus muscles of mice in the COPD state may negatively relate to a reduction in grip strength, but not bone loss. [ABSTRACT FROM AUTHOR]

Background: Rapid deterioration of oxygenation occurs in novel coronavirus disease 2019 (COVID-19), and prediction of mechanical ventilation (MV) is needed for allocation of patients to intensive care unit. Since intubation is usually decided based on varying clinical conditions, such as required oxygen changes, we aimed to elucidate thresholds of increase in oxygen demand to predict MV use within 12 h. Methods: A single-center retrospective cohort study using data between January 2020 and January 2021was conducted. Data were retrieved from the hospital data warehouse. Adult patients diagnosed with COVID-19 with a positive polymerase chain reaction (PCR) who needed oxygen during admission were included. Hourly increments in oxygen demand were calculated using two consecutive oxygen values. Covariates were selected from measurements at the closest time points of oxygen data. Prediction of MV use within 12 h by required oxygen changes was evaluated with the area under the receiver operating curves (AUCs). A threshold for increased MV use risk was obtained from restricted cubic spline curves. Results: Among 66 eligible patients, 1835 oxygen data were analyzed. The AUC was 0.756 for predicting MV by oxygen demand changes, 0.888 by both amounts and changes in oxygen, and 0.933 by the model adjusted with respiratory rate, PCR quantification cycle (Ct), and days from PCR. The threshold of increments of required oxygen was identified as 0.44 L/min/h and the probability of MV use linearly increased afterward. In subgroup analyses, the threshold was lower (0.25 L/min/h) when tachypnea or frequent respiratory distress existed, whereas it was higher (1.00 L/min/h) when viral load is low (Ct ≥20 or days from PCR >7 days). Conclusions: Hourly changes in oxygen demand predicted MV use within 12 h, with a threshold of 0.44 L/min/h. This threshold was lower with an unstable respiratory condition and higher with a low viral load. [ABSTRACT FROM AUTHOR]