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The transcription and transportation of mRNA are coupled processes; however, the mechanisms linking these processes remain unclear. Additionally, the significance of this connection in cancer drug development is poorly understood. To address these issues, we investigated the role of CDK12 kinase, which regulates RNA transcription through the phosphorylation of RNA polymerase II (Pol II) and has a repeated serine-arginine dipeptide (RS domain) involved in mRNA transport. Despite the anticipated uniqueness of CDK12 function, the mechanism by which CDK12 bridges and manages mRNA transcription and transport has not been fully analyzed. Our study revealed that CDK12 interacts with NXF1, a key molecule involved in the export of mRNA from the nucleus to the cytosol. Although CDK12 does not phosphorylate NXF1, we found that NXF1 unexpectedly stabilized the CDK12 protein, suggesting that NXF1 mRNA export activity indirectly affects mRNA transcriptional activity by modifying the protein level of CDK12. Furthermore, CDK12 recruited other essential RNA transporters, specifically the exon junction complex (EJC) and THO complexes, into the CDK12-NXF1 axis through its kinase activity. These observations provide insights into the mechanisms linking mRNA transcription and transport through the formation of a novel CDK12-NXF1 complex that involves EJC and THO. Importantly, the expression level of NXF1 influences sensitivity to CDK12 inhibitors, which are emerging as novel anti-cancer drug candidates. This highlights the importance of considering the relationship between mRNA transcription and transport when targeting RNA transcription in cancer therapy., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Daisuke Morishita reports a relationship with Chordia Therapeutics Inc. that includes: employment and equity or stocks. Shunsuke Ebara reports a relationship with Chordia Therapeutics Inc. that includes: employment and equity or stocks. Misaki Yoshida reports a relationship with Chordia Therapeutics Inc. that includes: employment. Hiroko Yamakawa reports a relationship with Chordia Therapeutics Inc. that includes: employment and equity or stocks. Kenichiro Shimokawa reports a relationship with Chordia Therapeutics Inc. that includes: employment and equity or stocks. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Background: Nintedanib is generally safe and well tolerated and can improve prognosis in patients with various interstitial lung diseases (ILDs). Appropriate management of adverse events of nintedanib is important to ensure its long-term persistent use. Weight loss is a routinely assessed adverse event in clinical practice. This study aimed to elucidate whether body weight change in the first year of nintedanib therapy can indicate prognosis and predict tolerability in patients with ILD., Methods: We analysed 245 consecutive ILD patients treated with nintedanib. We calculated the slope of body weight change using baseline weight and that recorded closest after the first year and then categorized percent change in body weight at this time. Significant weight loss was defined as that ≥5%., Results: Subjects included 67 patients with idiopathic pulmonary fibrosis (IPF) and 76 with non-IPF progressive fibrosing-ILD including fibrotic hypersensitivity pneumonitis (n = 16), unclassifiable (n = 35), connective tissue disease-ILD (n = 21), and nonspecific interstitial pneumonia (n = 4). Older age, low body weight at initial examination, significant weight loss, and lower %FVC were significant predictors of discontinuation of nintedanib. Patients with weight loss ≥5% over the first year showed worse survival than those with weight loss <5% regardless of whether IPF existed or BMI indicated obesity., Conclusions: Careful monitoring of body weight change might suggest useful information for predicting long-term use of nintedanib and mortality risk in ILD patients treated with nintedanib. Appropriate body weight management is needed to prevent adverse events of nintedanib itself., Competing Interests: Declaration of competing interest H.Y. and S.S. received honoraria from Nippon Boehringer Ingelheim Co., Ltd. The other authors have no conflicts of interest., (Copyright © 2024 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.)

Background: Pulmonary alveolar proteinosis (PAP) is characterized by an abnormal accumulation of surfactants in the alveoli. Most cases are classified as autoimmune PAP (APAP) because they are associated with autoantibodies against granulocyte-macrophage colony-stimulating factor (GM-CSF). However, GM-CSF autoantibody levels are unlikely to correlate with the disease severity or prognosis of APAP., Methods: We collected clinical records and measured 38 serum cytokine concentrations for consecutive patients with APAP. After exclusion of 21 cytokines because of undetectable levels, 17 cytokine levels were compared between low and high disease severity scores (DSSs). We also compared whole lung lavage (WLL)-free survival with cut-off values defined by receiver operating characteristic (ROC) curves of cytokine levels and WLL administration at 11 months., Results: Nineteen patients with APAP were enrolled in the study. Five were classified as DSS 1 or 2, while the others were classified as DSS 4 or 5. Comparison between DSS 1-2 and 4-5 revealed that the concentrations of IP-10 and GRO increased in the latter groups (p < 0.05). Fifteen patients underwent WLL. Comparison between those who underwent WLL within 11 months and the others showed that IP-10 and TNF-α were tended to be elevated in the former group (p = 0.082 and 0.057, respectively). The cut-off values of IP-10, 308.8 pg/mL and TNF-α, 19.1 pg/mL, defined by the ROC curves, significantly separated WLL-free survivals with log-rank analyses (p = 0.005)., Conclusions: The concentrations of IP-10 and GRO may reflect the DSSs of APAP. A combination of IP-10 and TNF-α levels could be a biomarker to predict WLL-free survival., Competing Interests: Declaration of competing interest The authors have no conflicts of interest., (Copyright © 2024 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.)

The prognosis of patients with connective tissue disease (CTD) has improved significantly in recent years, but interstitial lung disease (ILD) associated with connective tissue disease (CTD-ILD) remains a refractory condition, which is a leading cause of mortality. Because it is an important prognostic factor, many observational and interventional studies have been conducted to date. However, CTD is a heterogeneous group of conditions, which makes the clinical course, treatment responses, and prognosis of CTD-ILD extremely diverse. To summarize the current understanding and unsolved questions, the Japanese Respiratory Society and the Japan College of Rheumatology collaborated to publish the world's first guide focusing on CTD-ILD, based on the evidence and expert consensus of pulmonologists and rheumatologists, along with radiologists, pathologists, and dermatologists. The task force members proposed a total of 27 items, including 7 for general topics, 9 for disease-specific topics, 3 for complications, 4 for pharmacologic treatments, and 4 for non-pharmacologic therapies, with teams of 2-4 authors and reviewers for each item to prepare a consensus statement based on a systematic literature review. Subsequently, public opinions were collected from members of both societies, and a critical review was conducted by external reviewers. Finally, the task force finalized the guide upon discussion and consensus generation. This guide is expected to contribute to the standardization of CTD-ILD medical care and is also useful as a tool for promoting future research by clarifying unresolved issues., Competing Interests: Conflict of Interest Dr. Yasuhiro Kondoh received honoraria from Shionogi & Co.,Ltd. and Nippon Boehringer Ingelheim Co., Ltd. Takashi Ogura received honoraria from Shionogi & Co., Ltd. and Nippon Boehringer Ingelheim Co., Ltd.; grant support and/ or research funding from Nippon Boehringer Ingelheim Co., Ltd.; and subsidies or donations from Nippon Boehringer Ingelheim Co., Ltd. and the Mental Health Okamoto Memorial Foundation. Dr. Takafumi Suda received honoraria from AstraZeneca K.K. and Nippon Boehringer Ingelheim Co., Ltd.; grant support and/or research funding from AstraZeneca K.K. and Ono Pharmaceutical Co., Ltd.; subsidies or donations from Astellas Pharma Inc., MSD K.K., Daiichi Sankyo Co., Ltd., Taiho Pharmaceutical Co., Ltd., Nippon Boehringer Ingelheim Co., Ltd., Novartis Pharma K.K., and Pfizer Japan Inc. Dr. Hiromi Tomioka received honoraria from Nippon Boehringer Ingelheim Co., Ltd. Dr. Hirofumi Amano received grant support and/or research funding from Sumitomo Dainippon Pharma Co., Ltd. and Nippon Boehringer Ingelheim Co., Ltd.; subsidies or donations from Actelion Pharmaceuticals Japan Ltd., Asahi Kasei Pharma Corporation, Astellas Pharma Inc., AYUMI Pharmaceutical Corporation, Eisai Co., Ltd., MSD K.K., Taisho Pharma Co., Ltd., Takeda Pharmaceutical Co., Ltd., Mitsubishi Tanabe Pharma Corporation, Chugai Pharmaceutical Co., Ltd., Teijin Pharma Ltd., and Bayer Yakuhin, Ltd. Dr. Masaki Anraku belongs to endowed departments sponsored by Tokio Marine & Nichido Fire Insurance Co., Ltd. Dr. Takao Fujii, received honoraria from Asahi Kasei Pharma Corporation, Astellas Pharma Inc., AbbVie GK, Chugai Pharmaceutical Co., Ltd., Eisai Co., Ltd., Eli Lilly Japan K.K., Janssen Pharmaceutical K.K., Mitsubishi Tanabe Pharma Corporation, Novartis Pharma K.K., Pfizer Japan Inc., Ono Pharmaciutical Cooperation Co.,Ltd., and Nippon Boehringer Ingelheim Co., Ltd., and subsidies or donations from Asahi Kasei Pharma Corporation, AbbVie GK, Chugai Pharmaceutical Co., Ltd., Eli Lilly Japan K.K., Eisai Co., Ltd., Mitsubishi Tanabe Pharma Corporation, and Ono Pharmaciutical Cooperation Co., Ltd. Dr. Tomoyuki Fujisawa received grant support and/or research funding from Novartis Pharma K.K. Dr. Takahisa Gono received honoraria from Ono Pharmaceutical Co., Ltd. Dr. Masayoshi Harigai received honoraria from Chugai Pharmaceutical Co., Ltd. and subsidies or donations from Eisai Co., Ltd.; and belongs to endowed departments sponsored by AYUMI Pharmaceutical Corporation, Mitsubishi Tanabe Pharma Corporation, and Nippon Kayaku Co., Ltd. Dr. Yoshikazu Inoue received honoraria from Nippon Boehringer Ingelheim Co., Ltd. Dr. Takeshi Johkoh received honoraria from Nippon Boehringer Ingelheim Co., Ltd. Dr. Hideto Kameda received honoraria from Asahi Kasei Pharma Corporation, AbbVie GK, Eli Lilly Japan K.K., Mitsubishi Tanabe Pharma Corporation, Chugai Pharmaceutical Co., Ltd., Novartis Pharma K.K., Pfizer Japan Inc., Bristol-Myers Squibb K.K., Janssen Pharmaceutical K.K.; grant support and/or research funding from Astellas Pharma Inc., AbbVie GK, Gilead Sciences Inc., Novartis Pharma K.K., and Bristol-Myers Squibb K.K.; and subsidies or donations from Asahi Kasei Pharma Corporation, Astellas Pharma Inc., Eisai Co., Ltd., Mitsubishi Tanabe Pharma Corporation, and Chugai Pharmaceutical Co., Ltd. Dr. Kensuke Kataoka received honoraria from Nippon Boehringer Ingelheim Co., Ltd. Dr. Yasuhiro Katsumata received subsidies or donations from Mitsubishi Tanabe Pharma Corporation and Chugai Pharmaceutical Co., Ltd. Dr. Yasushi Kawaguchi received honoraria from Actelion Pharmaceuticals Japan Ltd. and Bayer Yakuhin, Ltd. Dr. Atsushi Kawakami received honoraria from Astellas Pharma Inc., AbbVie GK, Eisai Co., Ltd., MSD K.K., Ono Pharmaceutical Co., Ltd., Kissei Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., Mitsubishi Tanabe Pharma Corporation, Chugai Pharmaceutical Co., Ltd., Eli Lilly Japan K.K., and Pfizer Japan Inc.; grant support and/or research funding from Ono Pharmaceutical Co., Ltd., Daiichi Sankyo Co., Ltd., Taisho Pharmaceutical Co., Ltd., Eli Lilly Japan K.K., and Bristol-Myers Squibb K.K.; and subsidies or donations from Asahi Kasei Pharma Corporation, Astellas Pharma Inc., AbbVie GK, Ono Pharmaceutical Co., Ltd., Mitsubishi Tanabe Pharma Corporation, Chugai Pharmaceutical Co., Ltd., and Pfizer Japan Inc. Dr. Noboru Kitamura received subsidies or donations from Ono Pharmaceutical Co., Ltd. and Chugai Pharmaceutical Co., Ltd. Dr. Kazuhiro Kurasawa received grant support and/or research funding from Pfizer Japan Inc.; and subsidies or donations from Asahi Kasei Pharma Corporation and Mitsubishi Tanabe Pharma Corporation. Dr. Yutaro Nakamura received subsidies or donations from Nippon Boehringer Ingelheim Co., Ltd. Dr. Ran Nakashima received grant support and/or research funding from Takeda Pharmaceutical Co., Ltd. Dr. Yasuhiko Nishioka, received subsidies or donations from Asahi Kasei Pharma Corporation and Pfizer Japan Inc. Dr. Masaki Okamoto received honoraria from Nippon Boehringer Ingelheim Co., Ltd. Dr. Fumikazu Sakai received honoraria from AstraZeneca K.K., Ono Pharmaceutical Co., Ltd., and Nippon Boehringer Ingelheim Co., Ltd., and manuscript fees from Nippon Boehringer Ingelheim Co., Ltd. Dr. Shinji Sato received subsidies or donations from Asahi Kasei Pharma Corporation, Ono Pharmaceutical Co., Ltd., and Chugai Pharmaceutical Co., Ltd. Dr. Tohru Takeuchi received honoraria from Mitsubishi Tanabe Pharma Corporation and Bristol-Myers Squibb K.K. and subsidies or donations from Asahi Kasei Pharma Corporation, Eisai Co., Ltd., Mitsubishi Tanabe Pharma Corporation, and Teijin Pharma Ltd. Dr. Masataka Kuwana received patent royalties and/or licensing fees from Medical & Biological Laboratories Co., Ltd.; honoraria from Actelion Pharmaceuticals Japan Ltd., Astellas Pharma Inc., Ono Pharmaceutical Co., Ltd., Sanofi K.K., Takeda Pharmaceutical Co., Ltd., Mitsubishi Tanabe Pharma Corporation, Chugai Pharmaceutical Co., Ltd., Bayer Yakuhin, Ltd., and Janssen Pharmaceutical K.K.; grant support and/or research funding from Chugai Pharmaceutical Co., Ltd., Nippon Boehringer Ingelheim Co., Ltd., and Bayer Yakuhin, Ltd.; and subsidies or donations from Asahi Kasei Pharma Corporation, Astellas Pharma Inc., Ono Pharmaceutical Co., Ltd., Mitsubishi Tanabe Pharma Corporation, Chugai Pharmaceutical Co., Ltd., Nippon Shinyaku Co., Ltd., and Bayer Yakuhin, Ltd. Dr. Drs. Shigeki Makino, Noriyuki Enomoto, Hidenori Ichiyasu, Hideya Kitamura, Tomohiro Koga, Osamu Nishiyama, Susumu Sakamoto, Toshimasa Shimizu, Noboru Takayanagi, Reoto Takei, Tamiko Takemura, Yuko Toyoda, Hidehiro Yamada, Hideaki Yamakawa, Yasuhiko Yamano, and Yoshioki Yamasaki declare no conflicts of interest associated with this article., (Copyright © 2021 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.)

Background: Pirfenidone is an anti-fibrotic agent approved for idiopathic pulmonary fibrosis (IPF), and long-term treatment data and the effect of continuation after disease progression have been reported. The efficacy and safety of pirfenidone in fibrosing interstitial lung disease (ILD) patients without IPF have been recently reported in clinical trials; therefore, the benefits of long-term treatment are also expected. This study aims to analyze the long-term treatment data of pirfenidone and clarify the predictive factors for long-term use of pirfenidone in non-IPF patients., Methods: We retrospectively reviewed the records of consecutive fibrosing ILD patients who started using pirfenidone between 2008 and 2014., Results: Of the 266 fibrosing ILD patients, 167 patients had IPF, and 99 had non-IPF. Despite the non-significant differences in body size and pulmonary function between IPF and non-IPF patients, the non-IPF patients had better overall survival than the IPF patients (median 4.06 years vs. 2.09 years, p < 0.0001). In addition, the non-IPF patients had a significantly longer time to treatment discontinuation than the IPF patients (median 2.20 years vs. 1.20 years, p = 0.002). Multivariate logistic regression analysis for ≥2 years of use of pirfenidone showed that the percent predicted forced vital capacity (%FVC) and age were predictive factors common to both IPF and non-IPF patients., Conclusions: Our results indicate that non-IPF patients can continue using pirfenidone for longer durations than IPF patients. Initiation of pirfenidone for fibrosing ILD patients with higher %FVC and younger age would lead to long-term use of pirfenidone., Competing Interests: Conflict of interest T Katano, A Sekine, H Yamakawa, T Misumi, H Okabayashi, R Okuda, H Kitamura, S Komatsu, and E Hagiwara declare no potential conflicts of interest. S Ikeda, T Baba, and T Ogura received honoraria from Nippon Boehringer Ingelheim Co., Ltd, and T Ogura received honoraria from Shionogi Co. Ltd., (Copyright © 2021 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.)

Background: Interstitial lung disease (ILD) patients commonly become obese or overweight due to deteriorated daily living activities and the adverse effects of prednisolone. This study aimed to clarify the effect of weight loss on pulmonary function test (PFT) in ILD patients with obesity., Methods: Among all consecutive ILD patients with a body mass index (BMI) ≥ 27 kg/m 2 who received nutrition education for improving obesity between June 2014 and December 2018, we retrospectively included patients who successfully decreased their body weight by over 2 kg and underwent follow-up PFT within 6 months. The results of PFT at baseline and follow-up and the level of Krebs von den Lungen-6 (KL-6) were compared., Results: Eleven patients (5 men and 6 women; median BMI of 34.1 kg/m 2 ), were enrolled. For PFT at baseline, the percentages of forced vital capacity (%FVC), functional residual capacity (%FRC), and diffusing capacity of the lung for carbon monoxide (%DLCO) were 69.3%, 59.9%, and 54%, respectively. The median KL-6 was 1035 U/mL. The median interval from baseline to the follow-up PFTs was 41 days. Compared to the baseline results of PFT, %FVC, %FRC, and %DLCO significantly increased (p = 0.018, 0.0006, and 0.024, respectively), and the changes in body weight and FVC were strongly correlated (p = 0.0004). In addition, the median serum level of KL-6 at follow-up tended to decrease by 206.5 U/mL (p = 0.083)., Conclusion: In ILD patients with obesity, weight loss is important and potentially improves their disease course., Competing Interests: Conflict of Interest Dr. Ogura received honoraria from Boehringer Ingelheim and Shionogi Co. Ltd. The remaining authors have no conflict of interest to declare., (Copyright © 2020 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.)

An analytical approach using high-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) was developed to simultaneously detect Fagopyrum esculentum Moench (buckwheat) and cereals containing gluten (Triticum species including wheat and spelt, rye, barley, and oats) that were specified in regulations for food allergen labeling on processed foods. Trypsin-digested peptides were purified from different processed food commodities and heptapeptides derived from buckwheat 13S globulin (GFIVQAR, m/z 395.8 [precursor] > 177.0 [product]) and Triticum low molecular weight glutenin (QIPEQSR, m/z 429.3 [precursor] > 616.2 [product]) were specifically detected each species at levels as low as 0.050-0.056 µg/L and 0.028-0.032 µg/L, respectively. Detection of these synthetic peptides was quantitative to over 100 µg/L by reference to the synthetic peptide calibration curves and at recovery rates, 76.6 ± 4.1%-104.8 ± 17.1% and 82.4 ± 2.0%-105.8 ± 5.3%, for GFIVQAR and QIPEQSR, respectively, when 1-1,000 µg of these peptides were spiked into a retort tomato sauce for pasta or dried instant soup. In combination with LC-MS/MS detection methods specific to other cereals containing gluten (rye, barley, and oats), the developed analytical approach was applicable to a wide variety of processed food commodities for food allergen labeling., Competing Interests: Declaration of Competing Interest None., (Copyright © 2021. Published by Elsevier B.V.)

Background: Pleuroparenchymal fibroelastosis (PPFE) is a rare idiopathic interstitial pneumonia characterized by pleural and parenchymal involvements predominantly in the upper lobes. Unilateral upper-lung field pulmonary fibrosis (upper-PF) radiologically consistent with PPFE was recently reported in patients with a history of open thoracotomy and presented with impaired thoracic movements in the operated side with unknown mechanisms. This retrospective study aimed to elucidate the clinical and radiological courses and pathological findings of unilateral upper-PF., Methods: All the consecutive patients diagnosed as having unilateral upper-PF between March 2012 and April 2018 were included. Radiological images and clinical courses before and after the diagnosis were thoroughly reviewed., Results: Fourteen patients were included. Unilateral upper-PF was diagnosed after a median of 4.8 years from the open thoracotomy or video-assisted thoracic surgery for treating lung or esophageal cancer, or bronchiectasis. Before or at diagnosis, 12 (85.7%) of 14 patients developed aberrant intrathoracic/extrathoracic air suggestive of pleural fistula, although the degree was slight. Of note, the upper-PF lesion apparently deteriorated once aberrant air emerged in all the patients. After diagnosis, the upper-PF lesion transformed into cystic lesion in 9 patients, 4 of whom eventually developed pulmonary aspergillosis. The prognosis was poor, with a median overall survival of 49.3 months. The autopsy in one patient demonstrated findings consistent with PPFE and chronic pleuritis., Conclusions: Unilateral upper-PF developed after thoracic surgeries and had many clinical, radiological, and pathological characteristics in common with idiopathic PPFE. Our results indicate that the commonly observed aberrant air may be correlated with disease development and progression., Competing Interests: Conflict of interest All authors have no conflict of interest to declare., (Copyright © 2020 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.)

Background: Interstitial lung disease (ILD) is associated with high morbidity and mortality in patients with connective tissue disease (CTD). Because some patients with CTD overlap present with ILD first, with CTD diagnosed later, specific radiologic signs are needed to help differentiate each CTD or CTD-ILD from idiopathic ILD., Objectives: To determine whether specific CT findings can help differentiate CTD as rheumatoid arthritis (RA), systemic sclerosis (SSc), or polymyositis/dermatomyositis (PM/DM)., Methods: We analyzed 143 consecutive ILD patients with RA, SSc, or PM/DM. We assessed diagnostic accuracy of CT findings of CTD-ILD, CT pattern, and signs including "anterior upper lobe honeycomb-like lesion" and "low attenuation area (LAA) within an interstitial abnormality" for each CTD-ILD. Prognostic predictors were determined using Cox regression models., Results: Subjects were 78 patients with RA-ILD, 38 with SSc-ILD, 24 with PM/DM-ILD, and 3 with overlapping CTD-ILD. High frequency of anterior upper lobe honeycomb-like lesion suggests that CTD-ILD is due to RA-ILD (22%) rather than SSc-ILD (8%) or PM/DM-ILD (8%), whereas LAA within an interstitial abnormality suggests that CTD-ILD is due to SSc-ILD (26%) rather than RA-ILD (4%) or PM/DM-ILD (0%). Multivariate analysis showed that while not associated with survival, current or ex-smoker, honeycombing, and acute exacerbation were negative prognostic factors of mortality., Conclusions: The tendency is high for RA-ILD, in which anterior upper lobe honeycomb-like lesion is a specific feature, to show UIP or NSIP/UIP pattern, combined emphysema, and honeycombing; SSc-ILD to show NSIP pattern and LAA within an interstitial abnormality; and PM/DM-ILD to show NSIP pattern and non-honeycombing., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Reactive sulfur species (RSS), such as hydropersulfides and hydropolysulfides with high nucleophilicity, contain mobilized sulfur that readily captures xenobiotic electrophiles, leading to their sulfur adducts. We have previously reported that RSS produced by cystathionine γ-lyase (CSE) captures the electrophilic metal methylmercury (MeHg) to form inert sulfur adducts, which in turn play a critical role in the protection against MeHg-induced motor impairment in mice. However, the mechanism underlying this neuroprotective effect is not fully understood. Here, we addressed this using CSE-knockout mice. The cerebellum of CSE-knockout mice was more susceptible to MeHg than that of wild type mice. Moreover, these CSE-deficient mice exhibited a higher level of mercury accumulation in the brain. However, co-treatment with sodium tetrasulfide, an RSS able to capture MeHg, leading to the formation of its sulfur adducts, blocked the increased accumulation of mercury, motor dysfunction and mortality caused by CSE deficiency. Our findings suggest that capturing MeHg by RSS in association with its sulfur adduct formation is involved in the repression of the brain distribution and deleterious effects of MeHg., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Myositis and interstitial lung disease (ILD) frequently occur in patients with anti-aminoacyl-tRNA synthetase (ARS) antibodies. Nearly half of ARS-ILD patients have the acute or subacute form of the disease, and one-third of these patients show a deterioration in pulmonary function over the long-term course because of frequent recurrences and refractoriness to therapy. Several reports recently described different characteristics depending on the individual anti-ARS antibodies, and the anti-asparaginyl tRNA synthetase (KS) antibody was strongly linked to ILD rather than to myositis. We therefore hypothesized that KS-ILD may have clinical characteristics that differ from those of other ARS-ILDs. The aim of this study was to clarify the clinical, radiological, and pathological features of KS antibody-positive ILD., Methods: We retrospectively analyzed 19 consecutive patients with KS-ILD who underwent initial clinical measurements and high-resolution computed tomography and pathological assessments. We also analyzed disease behavior based on pulmonary function test results during the follow-up period., Results: Our KS-ILD cohort included patients with dermatomyositis (10.5%), primary Sjögren syndrome (5.3%), and idiopathic ILD (84.2%). Most patients presented with chronic onset (89.5%) and a nonspecific pattern of interstitial pneumonia at each radiological and pathological assessment (89.4% and 85.7%, respectively). The pulmonary function test results showed that the mean changes from the initial %forced vital capacity and %diffusing capacity of the lung for carbon monoxide at 3 years were 3.7% ± 2.9% and 9.35% ± 3.0%, respectively., Conclusions: Most KS-ILD patients showed a tendency for chronic disease onset and long-term stabilization of pulmonary function., (Copyright © 2020 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.)

Background: Some cases of idiopathic fibrotic nonspecific interstitial pneumonia (f-NSIP) show a progressive course that is similar to that of idiopathic pulmonary fibrosis. However, it is difficult to predict poor patient outcomes. This study aimed to evaluate whether serial changes in serum levels of Krebs von den Lungen-6 (KL-6) and surfactant protein-D (SP-D) can predict disease progression., Methods: We retrospectively analyzed the medical records of 75 patients with idiopathic f-NSIP. Disease behavior was categorized into two groups depending on long-term change of pulmonary function: progressive type (≥5%/year relative decline in the slope of forced vital capacity [FVC] and/or ≥7.5%/year relative decline in the slope of %diffusing capacity of the lung for carbon monoxide [%D LCO ]) and stable type. Levels of KL-6 and SP-D and results of pulmonary function tests, which were performed parallelly, were reviewed and analyzed using a linear mixed-effects model., Results: The study subjects comprised 62 patients with stable type and 13 patients with progressive type disease behavior. Among these subjects, 50 patients fulfilled the diagnostic criteria of interstitial pneumonia with autoimmune features (IPAF). Serum levels of both KL-6 and SP-D at baseline showed a negative correlation with %D LCO , but not with FVC, and these biomarkers were not related to disease progression. Persistently high levels of KL-6 and SP-D correlated with progressive type disease behavior in idiopathic (non-IPAF) f-NSIP., Conclusions: Changes in serum KL-6 and SP-D levels over time may provide useful predictive information on disease behavior during treatment in patients with idiopathic f-NSIP and especially in those with non-IPAF f-NSIP., (Copyright © 2019 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.)

This study investigated the molecular and phenotypic characteristics of carbapenemase-producing Klebsiella pneumoniae, and identified the risk factors underlying its acquisition. We evaluated K. pneumoniae isolated in Nagasaki University Hospital between January 2009 and June 2015. The presence of carbapenemase genes and plasmid characteristics were investigated. We performed multilocus sequence typing (MLST), and generated a dendrogram based on the results of pulsed-field gel electrophoresis (PFGE) for carbapenemase-producing strains. We also performed a case-control study of patients. Of the 88 K. pneumoniae strains that showed minimum inhibitory concentration ≥1 μg/mL for imipenem and/or meropenem, and that were available from our bacterial collection, 18 had the IMP-type carbapenemase gene, all of which were IMP-1 according to sequencing analysis. Strains included seven different sequence types (STs), of which the most common was ST1471. A dendrogram showed the significant similarity of some strains with relationships in PFGE patterns, STs, and the wards in which they were isolated. Plasmid incompatibility group was similar among the IMP-1 producers. Regarding risk factors, multivariate analysis showed that liver disease and previous uses of carbapenems and anti-fungal drugs were significant factors for the acquisition of IMP-1-producing strains. Our results demonstrate that IMP-1 is a major carbapenemase produced by K. pneumoniae. The PFGE results indicated the possibility of transmission in the hospital. The identified risk factors should be considered for appropriate antibiotic therapy and infection-control measures., (Copyright © 2018 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Background: The incidence of asymptomatic pulmonary Mycobacterium avium complex (MAC) disease appears to be increasing. This study aimed to determine the clinical characteristics and examine early outcomes of patients newly diagnosed with MAC disease., Methods: We retrospectively reviewed the medical records of all 184 patients newly diagnosed with MAC disease between April 2013 and March 2015 at our hospital. Culture conversion, defined as at least two consecutive negative cultures, was used as the early outcome measure., Results: Of 184 patients, 45 were male and 139 were female, with a mean age of 70 years. Abnormal chest shadow found during an annual health check-up (58 patients) or incidentally during visits for other diseases (72 patients), was the major reason for referral to hospital, typically with no symptoms. Anti-MAC IgA antibody was positive in 64.5% of patients, and the positive rate was associated with the extent of lesions. Clarithromycin-based multi-drug chemotherapy was initiated in 111 patients. Culture conversion was achieved in 61 of 82 (74.4%) patients who were able to continue multi-drug chemotherapy. Patients who achieved culture conversion were more likely to be younger, female, and have a lower smear grade and nodular-bronchiectatic type. Multivariate logistic regression analysis identified patient age and smear grade as predictive variables., Conclusions: Abnormal chest shadow found during health check-up was the major reason for hospital visits, and most were asymptomatic. Culture conversion was achieved in three-fourths of patients treated, and was associated with age and smear grade, supporting early intervention at a younger age., (Copyright © 2018 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.)

Two-component systems, versatile signaling mechanisms based on phosphate transfer between component proteins, must have played important roles in adaptation and diversification processes in land plant evolution. We previously demonstrated that two Per-Arnt-Sim (PAS)-histidine kinases, PHK1 and PHK2, repress gametophore formation in the moss Physcomitrella patens under aerobic conditions, and that, in eukaryotes, the presence of their homologs is restricted to early-diverging streptophyte linages. We assessed here whether or not PHKs play a role in oxygen signaling. When submerged under water, the double disruption line for PHK1 and PHK2 formed fewer gametophores than the wild-type line (WT) both under light-dark cycles or continuous light, indicating that PHKs promote gametophore formation under an aquatic environment, in contrast to aerobic conditions. Similarly, in an artificial low-oxygen condition, the double disruption line formed fewer gametophores than WT. These results indicate that PHKs exert dual and opposite effects on gametophore formation depending on oxygen status. This study adds important insight into functional versatility and evolutionary significance of two-component systems in land plants., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Ras-related small G-protein Rad plays a critical role in generating arrhythmias via regulation of the L-type Ca(2+) channel (LTCC). The aim was to demonstrate the role of Rad in intracellular calcium homeostasis by cardiac-Specific dominant-negative suppression of Rad. Transgenic (TG) mice overexpressing dominant-negative mutant Rad (S105N Rad TG) were generated. To measure intracellular Ca(2+) concentration ([Ca(2+)]i), we recorded [Ca(2+)]i transients and Ca(2+) sparks from isolated cardiomyocytes using confocal microscopy. The mean [Ca(2+)]i transient amplitude was significantly increased in S105N Rad TG cardiomyocytes, compared with control littermate mouse cells. The frequency of Ca(2+) sparks was also significantly higher in TG cells than in control cells, although there were no significant differences in amplitude. The sarcoplasmic reticulum Ca(2+) content was not altered in the S105N Rad TG cells, as assessed by measuring caffeine-induced [Ca(2+)]i transient. In contrast, phosphorylation of Ser(2809) on the cardiac ryanodine receptor (RyR2) was significantly enhanced in TG mouse hearts compared with controls. Additionally, the Rad-mediated RyR2 phosphorylation was regulated via a direct interaction of Rad with protein kinase A (PKA)., (Copyright © 2014 Elsevier Inc. All rights reserved.)

The Krüppel-associated box-containing zinc finger gene family (KRAB-ZNF) is one of the largest gene families of transcriptional factors in the human genome. Although the functions of most of these genes remain to be determined, it is known that KRAB-mediated transcriptional repression requires a direct interaction with the KAP1 co-repressor. By mammalian one- or two-hybrid experiments in HEK293 cells, we compared transcriptional repression activities of 61 human KRAB-ZNFs. The results showed that six SCAN-KRAB-containing ZNFs are KAP1-independent transcriptional repressors whose SCAN-KRAB domain is unable to associate with KAP1 despite retaining transcriptional repression activity. Transcriptional repression activities of the SCAN-KRAB domain of KAP1-independent KRAB-ZNFs are not influenced by depletion of endogenous KAP1 levels by small interfering RNA. Although the mechanism by which KAP1-independent KRAB-ZNFs repress transcriptional activity remains to be elucidated, it appears that there may be a pathway for transcriptional repression that does not involve KAP1. These results provide new insight into the functions of the members of the KRAB-ZNF family.

Objective: The precise etiology of perimesencephalic nonaneurysmal subarachnoid hemorrhage (P-SAH) has not yet been determined. We decided to compare the venograms of patients with P-SAH with those of patients with aneurysmal SAH (A-SAH) to examine the relationship between P-SAH and venous drainage patterns., Methods: We retrospectively studied 18 patients with P-SAH during the past 10 years and 112 patients with ruptured A-SAH during the past 4 years by reevaluating their venograms for possible abnormalities in venous structures, particularly focusing on the basal vein of Rosenthal (BVR). Anatomical variants were classified into three types according to the drainage pathway., Results: The location and drainage pathway of the BVR proved to be a significantly more primitive configuration in patients with P-SAH than in those with A-SAH (P<0.05). On the other hand, physical action including components of the Valsalva maneuver were the cause of nine cases of P-SAH (69.2%) in this case profile. The occurrence rate was significantly higher in the P-SAH group than in the A-SAH group (14.3%) (p<0.05)., Conclusion: Our data suggest that failure of longitudinal anastomoses between the primary primitive veins as well as excessive strenuous exertion including components of the Valsalva maneuver plays an important predisposing role in the etiology of P-SAH.

Recently, neuroligins (NLs)3 and 4X have received much attention as autism-related genes. Here, we identified syntrophin-gamma2 (SNTG2) as a de novo binding partner of NL3. SNTG2 also bound to NL4X and NL4Y. Interestingly, the binding was influenced by autism-related mutations, implying that the impaired interaction between NLs and SNTG2 contributes to the etiology of autism.

Background: Dissecting aneurysm of the posterior inferior cerebellar artery (PICA) uninvolved with the vertebral artery is rare. The exact pathohistological diagnosis might result in 'unknown' because the underlying pathoanatomical features are, for a variety of reasons, not always identified., Case Description: We report herein two cases of dissecting aneurysm harbored in different segments of the distal posterior inferior cerebellar artery. In our cases, after trapping the PICA at both just proximal and distal to the aneurysm, the abnormal portion was successfully resected with/without an end-to-end anastomosis. The first patient made a good recovery, while the other died 2 days after the surgery. Although its pathogenetic etiology was unidentified in the second case, the formation of dissecting aneurysm had resulted from a segmental mediolytic arteriopathy in the first case., Conclusion: This is the first report of a segmental mediolytic arteriopathy possibly being identified as causing an isolated dissecting aneurysm at this site.

The role of superoxide anion (O(2)*-) in neuronal cell injury induced by reactive oxygen species (ROS) was examined in PC12 cells using pyrogallol (1,2,3-benzenetrior), a donor to release O(2)*-. Pyrogallol induced PC12 cell death at concentrations, which evidently increased intracellular O(2)*-, as assessed by O(2)(*-)-sensitive fluorescent precursor hydroethidine (HEt). Caspase inhibitors, Z-VAD-FMK and Z-Asp-CH(2)-DCB, failed to protect cells from injury caused by elevation of intracellular O(2)*-, although these inhibitors had effects on hypoxia- or hydrogen peroxide (H(2)O(2))-induced PC12 cell death. Two known O(2)*- scavengers, Tiron (4,5-dihydroxy-1,3-benzenedisulfonic acid) and Tempol (4-hydroxy-2,2,6,6-tetramethylpiperydine-1-oxyl) rescued PC12 cells from pyrogallol-induced cell death. Hypoxia/reoxygenation injury of PC12 cells was also blocked by Tiron and Tempol. Further understanding of the underlying mechanism of the protective effects of these radical scavengers reducing intracellular O(2)*- on neuronal cell death may lead to development of new therapeutic treatments for hypoxic/ischemic brain injury., (Copyright 2002 Elsevier Science Ireland Ltd and the Japan Neuroscience Society)

Isolated plantar dislocation of the cuneiform was reported in only two cases in the literature. We report a 57-year-old man with plantar dislocation of the cuneiform when the foot was struck by a large concrete block during construction of a building. Tarsometatarsal injuries are frequently overlooked. Therefore, plain computed tomography (CT) and three-dimensional CT are useful for adequate evaluation.

Background: Therapeutic principles for managing subclinical pleural cancer found unexpectedly during intraoperative examination are unclear. We analyzed prognostic factors including the tumor proliferative marker Ki-67 in these circumstances., Methods: The cases of 65 surgically treated patients with lung cancer and subclinical T4 pleural cancer, microscopic in 25 and macroscopic in 40, were reviewed., Results: The overall 5-year survival rate of patients undergoing lobectomy was 14.3%. For patients with T4 NO disease, the 5-year survival rate was 46.7%. In patients with a low Ki-67 labeling index, the 5-year survival rate was 28.6%. The Ki-67 labeling index was a significant (p < 0.05) indicator of survival. Multivariate analysis demonstrated Ki-67 labeling index, lymph node involvement, and tumor differentiation to be the most influential prognostic factors for postoperative survival (p < 0.01)., Conclusions: In the treatment of lung cancer patients with subclinical pleural cancer found at thoracotomy, tumor resection is not necessarily contraindicated. Resection appears to be beneficial in patients with no nodal involvement or a low tumor Ki-67 labeling index. This index is a good therapeutic indicator for lung cancer patients.

High-performance liquid chromatography (HPLC) system with a new nonporous anion-exchange resin, DNA-NPR, made it possible to rapidly separate DNA fragments up to 20 kbp with high resolution. In order to further characterize this chromatographic DNA separation system, we prepared a mixture of double-stranded DNAs of constant length carrying a fully degenerated 50-bp region and analyzed their chromatographic behavior on the DNA-NPR column. The results indicated that the separation of DNA fragments on the anion-exchange HPLC was governed not only by size, but also by nucleotide sequence: even DNA fragments with the same size and the same base content could be separated on this column. Taking advantage of this characteristic feature of the anion-exchange HPLC, we could readily fractionate human cDNAs with practically acceptable recovery and high resolution. Furthermore, the combination of HPLC and gel electrophoresis realized separation of a mixture of DNA fragments in a two-dimensional pattern.

To assess the effect of dietary calcium (Ca) and salt on blood pressure and vascular reactivity, 5-week-old male spontaneously hypertensive rats were placed on control (1% Ca diet+tap water), high Na (1% NaCl administered in drinking fluid), low Ca (0.2% Ca diet), and low Ca+high Na intake for 3 weeks (n = 8-10). During the observation period, systolic blood pressure increased in all groups, but the increase was markedly enhanced in the low Ca+high Na group. There were no significant differences in body weight and serum electrolytes. On high Na intakes, urine volume and urinary Na excretion increased and plasma renin activity and aldosterone concentration were suppressed, whereas Ca restriction did not affect these values. The dose-response curves of mesenteric arterial beds for in vitro contraction to norepinephrine (NE) were not affected by dietary manipulations. However, the time from maximum contraction to return to baseline levels of contractility by 10(-4) M NE was significantly prolonged in the low Ca+high Na group. These results indicate that Ca restriction accelerates salt-induced hypertension in young spontaneously hypertensive rats, and the cellular impairment in vascular smooth muscle might, at least in part, participate in the enhanced blood pressure elevation under this condition.

To understand the underlying mechanism of force generation by myosin motor, it is crucial to know which part of the molecule is essential for the process. Recent structure determination of myosin motor domain at atomic resolution has revealed that the domain comprises two smaller domains, the "ATPase domain" consisting of only an N-terminal segment of the heavy chain and the "neck domain" consisting of a long alpha-helix of the heavy chain and two light chains. This atomic structure begs the question of whether both domains are required for force generation. To answer it, we genetically truncated the head to generate a recombinant fragment composed of the "ATPase domain" alone. The truncated head drove sliding movement of actin filaments and generated force in a novel in vitro assay system, which allows us to hold a specific site of the head on a glass surface. These results indicate that the compact ATPase domain functions as a force-generating machinery of the myosin motor.

The freezability of porcine peri-hatching stage blastocysts was investigated by the cryopreservation of embryos at -196 degrees C with 1.5 M glycerol and by thawing, followed by in vitro culture. Of 66 expanded blastocysts frozen, 34 (51.5%) developed in vitro after thawing, while only 2 (6.7%, P<0.05) of 30 earlier stage blastocysts survived freezing. After freezing of 85 hatched blastocysts with an embryonic diameter of 150 to 300 mum, 59 (69.4%) surviving embryos were obtained, whereas none of the 78 advanced staged hatched blastocysts (>300 mum) survived the cryopreservation. High post-thaw survival (32 39 , 82..1%) was obtained with in vitro-hatched blastocysts precultured in Whittingham's M-16 medium containing 12mg/ml bovine serum albumin (BSA). In contrast, none of the 14 in vitro-hatched blastocysts precultured in the M-16 medium supplemented with 15% fetal calf serum (FCS) survived freezing. Similarly 51 of 56 hatced blastocysts (diameter = 150 to 300 mum) precultured in the M-16 medium supplemented with BSA survived cryopreservation, compared with 3 of 26 embryos precultured in the medium supplemented with FCS (P<0.001). Because both groups of the embryos precultured with BSA or FCS possessed normal ability to develop after transfer (developmental rate = 61.1 and 93.3%), the improved freezability of the embryos precultured with BSA may relate to a favorable change of embryonic cell membranes during the culture period. It was concluded that in vitro-hatched blastocysts precultured in medium containing BSA and in vivo-hatched blastocysts at the appropriate stage of development could both tolerate deep freezing to -196 degrees C; however, a differece in the freezability of embryos between breeds of pig was suggested from a further experiment performed with German Landrace embryos.

Skeletal lesions are not uncommon in von Recklinghausen neurofibromatosis. Most of them are considered to be dysplastic in nature. Association of osteomalacia or rickets with neurofibromatosis has been documented only rarely. Reported herein is a 40-year-old woman with known von Recklinghausen neurofibromatosis who presented with bone pain, multiple pseudofractures, marked increase in osteoid by bone biopsy, and hypophosphatemia with renal phosphate wasting. Treatment with oral phosphate and vitamin D was effective. A survey of the literature revealed that 34 similar cases have been reported in the past. Although the exact pathogenetic mechanism remains to be determined, osteomalacia in neurofibromatosis appears to be distinct from more common dysplastic skeletal affections of this disease, being characterized by later onset in adulthood as a rule, renal phosphate loss with hypophosphatemia, multiple pseudofractures in typical cases, and response to treatment with pharmacological dose of vitamin D with or without phosphate supplement.

The survival of whole and bisected rabbit morulae cryopreserved by the vitrification method was investigated. The embryos were loaded in a column of vitrification solution (VS, a mixture of 25% glycerol and 25% 1, 2-propanediol in PBS+16% calf serum), which was located between two columns of 1 M sucrose solution in a plastic straw. The embryos were frozen by being plunged into liquid nitrogen and thawed in a water bath at 20 degrees C. Two methods of loading embryos into straws were used: the single and double column vitrification solution methods. The embryonic survival rates between these two methods were compared. Seventy-one (86.6%) out of 82 morulae vitrified in double column straws developed into the blastocyst stage in vitro. Eleven (18.3%) live fetuses were obtained after the transfer of 60 frozen-thawed morulae to four recipients. By contrast, the survival rate (36.5%, 27 74 ) of embryos vitrified in the single column straws was significantly lower (P<0.05). The vitrification solution of the single column straws became opaque, indicating ice-crystal formation, upon thawing in 5 of 11 straws, which was assumed to have damaged the embryos. More than 80% (29 36 ) of the bisected morulae frozen and thawed in the double column straws developed to the blastocyst stage in vitro when cryoprotectant was diluted stepwise with 1 M and 0.25 M sucrose solution. When the cryoprotectant was removed by one-step dilution with 1 M sucrose solution, swelling in blastomeres was observed and the development rate of the recovered embryos decreased (45.8%, 11 24 ). These results indicate that the vitrification method employed in our experiment is not only efficient for the cryopreservation of rabbit morulae, but it can also be used for the preservation of bisected rabbit morulae, which had not been successful using previous methods.

Recent experimental data of Shore & Baldwin (1983b) and of Horowitz & Wang (1984) for the apparent twisting coefficient K, which determines the breadth of the Gaussian distribution of DNA topoisomers with different linking numbers N, show that the product of K and nbp (the number of base-pairs) is nearly a constant for nbp approximately greater than 2000, but that it increases sharply with decreasing nbp for nbp approximately less than 2000. The main purpose of the present paper is to explain theoretically such behavior of K as a function of nbp. Thus the statistical mechanics of DNA topoisomers in general is developed on the basis of a twisted worm-like chain, i.e. a special case of the helical worm-like chain. The previous treatments of the N-dependent ring-closure probability, i.e. the distribution of N, which are valid only for small chain length L, are extended to the range of larger L. The variance of N is then shown to be exactly the sum of those of the writhe Wr and the twist Tw. For small values of L, the distribution of Wr is not Gaussian, and its variance or moment (Wr2) increases rather steeply with increasing L. With these and known Monte Carlo results for freely jointed chains, an empirical interpolation formula for (Wr2) is also constructed to be valid for all values of L. It predicts that (Wr2)/L increases monotonically, with increasing L to its coil-limiting value. On the other hand, the distribution of N is actually Gaussian in the practical range of N for all values of L. The conditional distribution of Wr with N fixed is also evaluated. Finally, K is expressed in terms of the torsional constant C, the stiffness parameter lambda-1 (which is equal to the Kuhn segment length and twice the persistence length for this special case), and (Wr2). The derived equation predicts that nbpK decreases monotonically to its coil-limiting value with increasing nbp. This decrease arises from the fluctuation in Wr and its neglect leads to an underestimate of C by 7 to 10%, even for short DNA with nbp approximately equal to 200. From an analysis of the experimental data of the two groups, the estimates of C = 3.1 to 3.2 X 10(-19) erg cm and lambda-1 = 1000 to 1200 A are obtained.

An attempt was made to detect the fluorescent bodies (F-body), using Quinacrine mustard (Q-M) staining in the spermatozoa from eight mammalian species (human, bull, boar, dog, rabbit, rat, mouse, and mastomys) as well as in the cock (used as negative control). Sperm suspension, prepared after rinsing by repeated centrifugation with phosphate buffered saline (PBS), was either stained with Q-M for 24 h or treated with protease and then stained with Q-M for 60 min. The final concentration of Q-M in the mixed staining sperm suspension was 0.025 mg/ml. The examination using a reflecting fluorescent microscope revealed that the F-body found in human sperm was also present in the sperm of all the mammals but not in the cock after 24 h of staining. The enzyme-treated specimens showed higher incidences of F-bodies than specimens stained for 24 h without enzymatic digestion. These findings strongly suggest that the F-body is commonly present in the spermatozoa of many mammalian species.