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Large ileal lipomas over 2 cm can cause symptoms, that may require a resection. Due to the narrow lumen and thin walls of the ileum, endoscopic treatments can have a high risk of adverse events and require technical expertise, thus surgical resection is currently the mainstay of treatment. To overcome the technical challenges, we developed a novel method to endoscopically resect terminal ileal lipomas. The technique involves extracting the lesion into the cecum, which creates sufficient space to maneuver, and a better field of view. The lipoma is resected with endoscopic mucosal resection or endoscopic submucosal dissection. The appearance of the lipoma protruding out of the ileocecal valve resembles that of a tongue sticking out of the mouth, thus we named this the "tongue out technique". To assess the technical feasibility of this method, we retrospectively analyzed seven cases of terminal ileal lipoma that were endoscopically resected using the "tongue out technique" at NTT Medical Center Tokyo between January 2017 and October 2023. Technical success was 100% and en bloc resection was achieved in all cases. The median size was 31 (14-55) mm. Three cases were resected with endoscopic mucosal resection while endoscopic submucosal dissection was performed on the other four cases. There was one case of delayed post-endoscopic mucosal resection bleeding, which was caused by clip dislodgement. There were no perforations. No recurrence of the lipoma or associated symptoms have been observed. This new technique can allow more ileal lipomas to be treated with minimally invasive and organ-preserving endoscopic procedures., Competing Interests: None., (© 2024 The Authors. DEN Open published by John Wiley & Sons Australia, Ltd on behalf of Japan Gastroenterological Endoscopy Society.)

Competing Interests: The authors disclosed no financial relationships relevant to this publication.

Objectives: Previous studies of cold snare polypectomy (CSP) for sessile serrated lesions (SSLs) ≥10 mm were performed by experienced endoscopists, and therefore their skills might have significantly influenced results. In this study, we compared the efficacy and safety of CSP for SSLs ≥10 mm between experienced and trainee endoscopists., Methods: In a 1:1 propensity score matched retrospective cohort study, we compared the complete resection rate, en-bloc resection rate, adverse event rate, and procedure time between experienced and trainee groups. Thirteen endoscopists performed CSP, and we defined the experienced group as endoscopists with board certification from the Japan Gastroenterological Endoscopy Society., Results: We examined 616 lesions with SSLs ≥10 mm resected by CSP between February 2018 and May 2022. We excluded 61 lesions from the analysis because they had simultaneously undergone hot snare polypectomy ( n = 57) or had been taken over by experienced endoscopists from trainees in the CSP procedure ( n = 4). Finally, we identified 217 propensity score-matched pairs ( n = 434). Between experienced and trainee groups, the results were complete resection rate (100 vs. 100%; p = 1.00), en-bloc resection rate (73.2 vs. 75.6%; p = 0.24), adverse event rate (3.2 vs. 2.8%; p = 0.77), or procedure time (6.2 vs. 5.9 min; p = 0.64)., Conclusions: We have demonstrated the safety and efficacy of CSP for SSLs ≥10 mm performed by experienced and trainee endoscopists., Competing Interests: None., (© 2024 The Authors. DEN Open published by John Wiley & Sons Australia, Ltd on behalf of Japan Gastroenterological Endoscopy Society.)

Background and study aims Endoscopic treatment strategies for small superficial duodenal epithelial neoplasia (SDET) have not been established, and the R0 resection rates of all previously reported endoscopic techniques are somewhat low. Furthermore, no reports of cap-assisted endoscopic mucosal resection (EMRC), which is reportedly associated with a relatively high R0 resection rate, have been evaluated in sufficient numbers of patients. Therefore, we assessed the efficacy and safety of EMRC for SDETs ≤ 10 mm in a retrospective cohort study. Patients and methods We examined a prospectively maintained database and identified 248 consecutive patients (248 lesions) who had undergone endoscopic resection for SDETs ≤ 10 mm between January 2017 and June 2022. Our treatment strategy was consistent, with EMRC indicated for all SDETs ≤ 10 mm without non-lifting signs. The primary endpoint was the R0 resection rate. Results Overall, 20 lesions had non-lifting signs and were selected for endoscopic submucosal dissection, while the remaining 228 lesions were treated with EMRC. As a result of EMRC, the median tumor size was 5 mm, and the mean procedure time was 5 minutes. Most of the lesions (89.2%) were located in the descending part. The R0 resection rate was 97.4% (222/228 cases), and the en bloc resection rate was 99.6%. Only seven patients(3.1%) experienced adverse events (6 patients, delayed bleeding; 1 patient, acute pancreatitis), which were successfully managed without surgical intervention. Furthermore, no recurrences were observed. Conclusions We have demonstrated that EMRC is an effective and safe treatment for SDETs ≤ 10 mm that do not have non-lifting signs., Competing Interests: Conflict of Interest The authors declare that they have no conflict of interest., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)

Background: Perigastric abscess caused by delayed perforation after endoscopic submucosal dissection is a very rare complication. In principle, delayed perforation after endoscopic submucosal dissection is treated surgically. Herein, we report a case of perigastric abscess caused by delayed perforation after gastric endoscopic submucosal dissection that was treated conservatively, without perforation closure, and in which the patient was discharged from hospital in a short period., Case Presentation: A-74-year-old Asian man was diagnosed with having early gastric cancer on follow-up endoscopy and was admitted to our hospital for endoscopic resection. Endoscopic submucosal dissection was performed without intraoperative complications. On postoperative day 2, the patient complained of a slight abdominal pain localized to the epigastric region and a small amount of melena. A computed tomography scan revealed the presence of free air in the peritoneal cavity, and a little fluid collection abutting the dorsal area of the stomach. An endoscopy examination showed a deep ulcer with the accumulation of pus, suggesting a perforation in the post-endoscopic submucosal dissection ulcer. We diagnosed a perigastric abscess, caused by delayed perforation after endoscopic submucosal dissection, and opted for conservative treatment, leaving the perforation site open to allow spontaneous drainage from the abscess into the stomach. A follow-up computed tomography scan revealed an encapsuled and localized perigastric abscess on postoperative day 5, and the disappearance of the free air and the regression of the perigastric abscess on postoperative day 7. A follow-up endoscopy examination on postoperative day 7 showed the closure of the perforation. Finally, surgery was avoided, and the patient was discharged on postoperative day 14, after a relatively short hospital stay., Conclusion: Regarding the treatment of perigastric abscess, caused by delayed perforation after endoscopic submucosal dissection, leaving the perforation site open to allow spontaneous drainage may shorten the conservative treatment period., (© 2023. The Author(s).)

Objective Pancreatic cystic lesions (PCLs) are known risk factors for pancreatic cancer. Therefore, this study explored the predictors identifying PCLs in a general population and developed a scoring system to help more efficiently diagnose these entities during medical checkups. Methods We reviewed 9,369 examinees of abdominal ultrasound (AUS) during medical checkups between January 2013 and November 2019. Predictors of PCLs were identified using a multivariate logistic regression analysis, and we constructed a scoring system based on these predictors. Results PCLs were detected in 118 (1.3%). Age 50-59 years old [odds ratio (OR) 2.52, 95% confidence interval (CI) 1.18-5.35], 60-69 years old (OR 3.91, 95% CI 1.86-8.26), and ≥70 years old (OR 10.5, 95% CI 5.03-21.7) as well as abdominal pain (OR 1.85, 95% CI 1.14-3.00), alcohol consumption (OR 1.72, 95% CI 1.03-2.89), a family history of pancreatic cancer (OR 2.41, 95% CI 1.09-5.34), and pre-diabetes or diabetes (OR 1.78, 95% CI 1.05-3.00) were predictors of PCLs. The following scores were assigned according to regression coefficients: age (50-59 years old, 1 point; 60-69 years old, 1.5 points; ≥70 years old, 2.5 points); abdominal pain, 1 point, alcohol consumption, 1 point; a family history of pancreatic cancer, 1 point; and pre-diabetes, 1 point. The PCL detection rate increased with the total score: 0.2% for total score 0 point, 5.4% for ≥4.0 points. The area under the curve of the scoring system was 0.75 (95% CI 0.70-0.79). Conclusion Our scoring system allows the risk of PCLs to be determined and may help more efficiently diagnose these entities.

Background: Gastric mixed neuroendocrine-non-neuroendocrine neoplasms are rare malignant tumors. The lack of specific findings makes it difficult to diagnose endoscopically. We report the case of early gastric mixed neuroendocrine-non-neuroendocrine neoplasms treated by endoscopic submucosal dissection., Case Presentation: An 81-year-old Japanese female underwent esophagogastroduodenoscopy for screening and was treated with endoscopic submucosal dissection for the diagnosis of early gastric cancer. Histopathologically, the lesion was diagnosed as mixed neuroendocrine-non-neuroendocrine neoplasms (tubular adenocarcinoma 2 60%, endocrine cell carcinoma 40%), pT1b(submucosa (SM) 900 μm), pUL(-), Ly(+), v(-), pHM0, pVM0. After additional surgical resection without adjuvant chemotherapy, she has had no recurrences or metastases for 3 years., Conclusions: Comparing narrow-band imaging magnified endoscopic findings with pathological findings, the depressed area with a lack of surface structure was consistent with the neuroendocrine cell carcinoma component, while narrow-band imaging magnification findings showed non-network vessels. In this case, we examined endoscopic findings of early stage mixed neuroendocrine-non-neuroendocrine neoplasms in detail and compared it with the pathological findings. We believe that these endoscopic findings contribute to the diagnosis of mixed neuroendocrine-non-neuroendocrine neoplasms and can lead to its early detection., (© 2022. The Author(s).)

During meiotic prophase, cohesin-dependent axial structures are formed in the synaptonemal complex (SC). However, the functional correlation between these structures and cohesion remains elusive. Here, we examined the formation of cohesin-dependent axial structures in the fission yeast Schizosaccharomyces pombe. This organism forms atypical SCs composed of linear elements (LinEs) resembling the lateral elements of SC but lacking the transverse filaments. Hi-C analysis using a highly synchronous population of meiotic S. pombe cells revealed that the axis-loop chromatin structure formed in meiotic prophase was dependent on the Rec8 cohesin complex. In contrast, the Rec8-mediated formation of the axis-loop structure occurred in cells lacking components of LinEs. To dissect the functions of Rec8, we identified a rec8-F204S mutant that lost the ability to assemble the axis-loop structure without losing cohesion of sister chromatids. This mutant showed defects in the formation of the axis-loop structure and LinE assembly and thus exhibited reduced meiotic recombination. Collectively, our results demonstrate that the Rec8-dependent axis-loop structure provides a structural platform essential for LinE assembly, facilitating meiotic recombination of homologous chromosomes, independently of its role in sister chromatid cohesion., (© The Author(s) 2022. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Meiosis is critically different from mitosis in that during meiosis, pairing and segregation of homologous chromosomes occur. During meiosis, the morphology of sister chromatids changes drastically, forming a prominent axial structure in the synaptonemal complex. The meiosis-specific cohesin complex plays a central role in the regulation of the processes required for recombination. In particular, the Rec8 subunit of the meiotic cohesin complex, which is conserved in a wide range of eukaryotes, has been analyzed for its function in modulating chromosomal architecture during the pairing and recombination of homologous chromosomes in meiosis. Here, we review the current understanding of Rec8 cohesin as a structural platform for meiotic chromosomes.

The nuclear envelope (NE) consists of the inner and outer nuclear membranes (INM and ONM), and the nuclear pore complex (NPC), which penetrates the double membrane. ONM continues with the endoplasmic reticulum (ER). INM and NPC can interact with chromatin to regulate the genetic activities of the chromosome. Studies in the fission yeast Schizosaccharomyces pombe have contributed to understanding the molecular mechanisms underlying heterochromatin formation by the RNAi-mediated and histone deacetylase machineries. Recent studies have demonstrated that NE proteins modulate heterochromatin formation and functions through interactions with heterochromatic regions, including the pericentromeric and the sub-telomeric regions. In this review, we first introduce the molecular mechanisms underlying the heterochromatin formation and functions in fission yeast, and then summarize the NE proteins that play a role in anchoring heterochromatic regions and in modulating heterochromatin formation and functions, highlighting roles for a conserved INM protein, Lem2.

Colorectal involvement is very rare in cases of follicular lymphoma. Colonoscopy of a 69-year-old man revealed an aggregation of multiple whitish nodules in the sigmoid colon. Magnifying endoscopy with narrow-band imaging demonstrated a coiled and elongated microvascular pattern on the surface and crystal violet staining showed a type I pit pattern. A biopsy showed follicular lymphoma (Grade 1), and no other involvement of lymphoma was detected. Following a diagnosis of primary colorectal follicular lymphoma stage I (Lugano classification), the patient was monitored by watch-and-wait therapy. We documented the endoscopic images of colorectal follicular lymphoma in the present case.

Cdb4 is a protein with unknown functions that binds to curved DNA in vitro in the fission yeast Schizosaccharomyces pombe. Homologues of Cdb4 were identified in a wide range of eukaryotes, including human Ebp1. Both S. pombe Cdb4 and human Ebp1 are nonpeptidase members of the methionine aminopeptidase family. It has been reported that Ebp1 homologues are involved in cell growth regulation and differentiation. However, opposing functions have also been considered and debated upon, and the precise biological functions of this conserved protein are largely unknown. S. pombe cdb4 is a nonessential gene, and no obvious phenotypes have been detected in cells with cdb4 gene deletion. In this study, we identified nup184, encoding a component of the nuclear pore complex, as a gene responsible for the synthetic lethal phenotype associated with cdb4. Furthermore, the synthetic lethal phenotype of Cdb4 was suppressed by over-expression of human Ebp1, suggesting that it has conserved crucial functions in S. pombe Cdb4 and human Ebp1. This synthetic lethal phenotype associated with Cdb4 and Nup184 provides a molecular genetics tool to study the functions of S. pombe Cdb4 and its conserved members of proteins, including human Ebp1., (© 2020 Molecular Biology Society of Japan and John Wiley & Sons Australia, Ltd.)

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A 49-year-old man was admitted to our hospital with pancreatitis. He was diagnosed with systemic lupus erythematosus at 34 years of age and was being treated with oral tacrolimus (3 mg/day) and predonine (10 mg/day) for the past 15 months. The computed tomography (CT) scan showed the mass lesion had invaded the pancreatic head via thickening of the duodenal wall. Upper gastrointestinal endoscopy showed the all-round ulcerative lesion from the superior duodenal angle to the descending portion. Histological examination confirmed the diagnosis of diffuse large B cell lymphoma (DLBCL). Tacrolimus therapy was stopped due to the possibility of immunodeficiency-related lymphoproliferative disease; however, the lesion did not improve. Consequently, he was administered rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). After six courses of R-CHOP therapy, a partial response was confirmed on CT. One month after the completion of chemotherapy, a gastrojejunal anastomosis was performed because of duodenal stenosis. He has since been well without recurrence. It was difficult to identify the risk factor for DLBCL; therefore, both the disease activity and immunosuppressive therapy should be taken into consideration as carrying a risk. In the present case, the symptom of pancreatitis enabled an early diagnosis of DLBCL.

We compared the sample volume of endoscopic ultrasound-guided fine-needle aspiration and biopsy (EUS-FNAB) specimens obtained by 22-gauge (22G) and 25-gauge (25G) needles, and the accuracy rate.This was a retrospective study in a single tertiary referral center. We investigated 153 patients with pancreatic ductal adenocarcinoma (PDAC) who underwent diagnostic EUS-FNAB before neoadjuvant gemcitabine-based chemoradiotherapy between October 2006 and November 2015. We performed immunohistochemical (IHC) analysis of human equilibrative nucleoside transporter 1 using the remnant cell blocks following pathological PDAC diagnosis. We compared the sampling rate, accuracy rate, and success rate of IHC analysis between 22G and 25G.There were 70 patients in the 22G group and 83 patients in the 25G group. The overall sampling rates on cytology and histology were 100% and 98.0%, respectively. The sampling rate did not differ between the 22G and 25G groups. The overall diagnostic accuracy rates on cytology and histology were 94.8% and 79.7%, respectively. The accuracy rates of 22G and 25G groups on cytology were 94.3% and 95.2%, respectively, whereas those on histology were 80.0% and 79.5%, respectively. The diagnostic accuracy on cytology and histology did not differ significantly between the 22G and 25G groups. Of 153 histology specimens, 69.3% of those with PDAC provided sufficient samples for IHC analysis. The success rate of IHC analysis did not differ significantly between the 22G (67.1%) and 25G (71.1%) groups (P = .60).Both 22G and 25G provided a high diagnostic yield with equivalent accuracy rates on histology. EUS-FNAB specimens obtained using 22G or 25G can be equally adequate for IHC analysis and may be suitable for diagnostic examination. Further investigations such as EUS-FNAB needle design and novel cell block preparation are needed to obtain adequate samples for use in "precision medicine."

Meiosis is a specialized cell cycle that generates haploid gametes from diploid cells. The fission yeast Schizosaccharomyces pombe is one of the best model organisms for studying the regulatory mechanisms of meiosis. S. pombe cells, which normally grow in the haploid state, diploidize by conjugation and initiate meiosis when starved for nutrients, especially nitrogen. Following two rounds of chromosome segregation, spore formation takes place. The switch from mitosis to meiosis is controlled by a kinase, Pat1, and an RNA-binding protein, Mei2. Mei2 is also a key factor for meiosis-specific gene expression. Studies on S. pombe have offered insights into cell cycle regulation and chromosome segregation during meiosis. Here we outline the current understanding of the molecular mechanisms regulating the initiation and progression of meiosis, and introduce methods for the study of meiosis in fission yeast., (© 2017 Cold Spring Harbor Laboratory Press.)

This protocol describes the live observation of chromosome segregation during fission yeast meiosis. To visualize one chromosome of interest, the lac operator ( lacO array) is integrated at its centromere-proximal locus, and the lac repressor (lacI)-GFP fusion protein is expressed in a haploid strain. This haploid strain, in which mCherry-tagged tubulin is also expressed exogenously to monitor meiotic progression, is crossed with a nonlabeled haploid strain to induce meiosis. GFP and mCherry signals in resulting zygotes are observed by a fluorescent microscopy during the progression of meiosis., (© 2017 Cold Spring Harbor Laboratory Press.)

Schizosaccharomyces pombe cells initiate a sexual differentiation program, which comprises meiosis and spore formation, on nitrogen starvation. This protocol describes a simple procedure to induce meiosis and sporulation semisynchronously in heterozygous diploid S. pombe cells. The procedure is appropriate for a variety of applications, including fluorescence-activated cell sorting (FACS) and northern and western blotting. Zygotic meiosis can also be induced by the same procedure, although less synchronously., (© 2017 Cold Spring Harbor Laboratory Press.)

In fission yeast Schizosaccharomyces pombe, initiation of meiosis is repressed by Pat1 kinase. This protocol describes how ectopic inactivation of the temperature-sensitive Pat1-114 kinase in G 1 -arrested h - / h - diploid cells carrying mat1-Pc induces a highly synchronized commitment to and execution of meiosis. Haploid or diploid pat1 -114 mutants without mat1-Pc can also be used for convenience, although less synchrony may be attained compared with induction using true diploids. An essentially identical protocol can be used for induction via inhibition of genetically sensitized Pat1 kinase by ATP analogs., (© 2017 Cold Spring Harbor Laboratory Press.)

In meiosis I, sister chromatids are captured by microtubules emanating from the same pole (mono-orientation), and centromeric cohesion is protected throughout anaphase. Shugoshin, which is localized to centromeres depending on the phosphorylation of histone H2A by Bub1 kinase, plays a central role in protecting meiotic cohesin Rec8 from separase cleavage. Another key meiotic kinetochore factor, meikin, may regulate cohesion protection, although the underlying molecular mechanisms remain elusive. Here, we show that fission yeast Moa1 (meikin), which associates stably with CENP-C during meiosis I, recruits Plo1 (polo-like kinase) to the kinetochores and phosphorylates Spc7 (KNL1) to accumulate Bub1. Consequently, in contrast to the transient kinetochore localization of mitotic Bub1, meiotic Bub1 persists at kinetochores until anaphase I. The meiotic Bub1 pool ensures robust Sgo1 (shugoshin) localization and cohesion protection at centromeres by cooperating with heterochromatin protein Swi6, which binds and stabilizes Sgo1. Furthermore, molecular genetic analyses show a hierarchical regulation of centromeric cohesion protection by meikin and shugoshin that is important for establishing meiosis-specific chromosome segregation. We provide evidence that the meiosis-specific Bub1 regulation is conserved in mouse., (© 2017 Molecular Biology Society of Japan and John Wiley & Sons Australia, Ltd.)

The kinetochore is the key apparatus regulating chromosome segregation. Particularly in meiosis, unlike in mitosis, sister kinetochores are captured by microtubules emanating from the same spindle pole (mono-orientation), and sister chromatid cohesion mediated by cohesin is protected at centromeres in the following anaphase. Shugoshin, which localizes to centromeres depending on the phosphorylation of histone H2A by Bub1 kinase, plays a central role in protecting meiotic cohesin Rec8 from separase cleavage. Another key meiotic kinetochore factor, Moa1 (meikin), which was initially characterized as a mono-orientation factor in fission yeast, also regulates cohesion protection. Moa1, which associates stably with CENP-C during meiosis I, recruits Plo1 (polo-like kinase) to the kinetochores and phosphorylates Spc7 (KNL1), inducing the persistent accumulation of Bub1 at kinetochores. The meiotic Bub1 pool ensures robust Sgo1 (shugoshin) localization and cohesion protection at centromeres by cooperating with heterochromatin protein Swi6, which binds and stabilizes Sgo1. Further, molecular genetic analyses reveal a hierarchical regulation of centromeric cohesion protection by meikin and shugoshin during meiosis I., (© 2017 Miyazaki et al.; Published by Cold Spring Harbor Laboratory Press.)

A 57-year-old man with a history of tuberculosis (TB) was found to have a pancreatic head mass, accompanied by stenosis of the common bile duct. Due to the inherent difficulty in differentiating pancreatic carcinoma from an inflammatory mass, endoscopic ultrasound-guided fine-needle aspiration biopsy (EUS-FNAB) was thus performed. The pathological findings confirmed granuloma with caseous necrosis, and the results of the QuantiFERON TB2G test were positive. Accordingly, the patient was diagnosed with peripancreatic TB and thereafter was successfully treated with anti-TB therapy. Based on the findings of this case, we conclude that EUS-FNAB is a useful modality for the diagnosis of pancreatic TB.

A retrospective cohort study was conducted in 55 symptomatic patients with amebic colitis that visited at St. Luke's International Hospital and Mie University Hospital from 1994 through 2013. To diagnose amebic colitis, 40 patients underwent total colonoscopy within 1 week after hospital visiting and before receiving any treatment. The percentage of characteristic endoscopic findings of amebic colitis including discrete ulcers or erosions with white or yellow exudates were 0% in terminal ileum, 93% in cecum, 28% in ascending, 25% in transverse, 15% in descending, 20% in sigmoid colon and 45% in rectum. The rectal lesions in 55% of patients with amebic colitis were nonspecific. The trophozoite identification rate by direct smear of intestinal tract washings performed during colonoscopy was 88%. The protozoan identification rate was 70% in biopsy specimens taken from the periphery of the characteristic discrete ulcers. Total colonoscopy should be considered for the diagnosis of amebic colitis., (Copyright © 2015 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

In meiosis, cohesin is required for sister chromatid cohesion, as well as meiotic chromosome axis assembly and recombination. However, mechanisms underlying the multifunctional nature of cohesin remain elusive. Here, we show that fission yeast casein kinase 1 (CK1) plays a crucial role in assembling the meiotic chromosome axis (so-called linear element: LinE) and promoting recombination. An in vitro phosphorylation screening assay identified meiotic cohesin subunit Rec11/SA3 as an excellent substrate of CK1. The phosphorylation of Rec11 by CK1 mediates the interaction with the Rec10/Red1/SCP2 axis component, a key step in meiotic chromosome axis assembly, and is dispensable for sister chromatid cohesion. Crucially, the expression of Rec11-Rec10 fusion protein nearly completely bypasses the requirement for CK1 or cohesin phosphorylation for LinE assembly and recombination. This study uncovers a central mechanism of the cohesin-dependent assembly of the meiotic chromosome axis and recombination apparatus that acts independently of sister chromatid cohesion., (Copyright © 2015 Elsevier Inc. All rights reserved.)

The kinetochore is the crucial apparatus regulating chromosome segregation in mitosis and meiosis. Particularly in meiosis I, unlike in mitosis, sister kinetochores are captured by microtubules emanating from the same spindle pole (mono-orientation) and centromeric cohesion mediated by cohesin is protected in the following anaphase. Although meiotic kinetochore factors have been identified only in budding and fission yeasts, these molecules and their functions are thought to have diverged earlier. Therefore, a conserved mechanism for meiotic kinetochore regulation remains elusive. Here we have identified in mouse a meiosis-specific kinetochore factor that we termed MEIKIN, which functions in meiosis I but not in meiosis II or mitosis. MEIKIN plays a crucial role in both mono-orientation and centromeric cohesion protection, partly by stabilizing the localization of the cohesin protector shugoshin. These functions are mediated mainly by the activity of Polo-like kinase PLK1, which is enriched to kinetochores in a MEIKIN-dependent manner. Our integrative analysis indicates that the long-awaited key regulator of meiotic kinetochore function is Meikin, which is conserved from yeasts to humans.

Objective: To evaluate sonographic measurements of visceral and subcutaneous fat in children, and to investigate the usefulness of preperitoneal fat (PF) and the abdominal wall fat index (AFI) as parameters to determine visceral fat and presence of nonalcoholic fatty liver disease (NAFLD) in obese children., Materials and Methods: A case-control study of a sample including 44 children (22 cases and 22 controls) matched by sex and age. The Student t test and the Fisher exact test were utilized in the descriptive and bivariate analysis., Results: The sonographic parameters evaluated - subcutaneous cell tissue, PF and intraperitoneal fat, and NAFLD - presented high statistical association with body mass index. NAFLD was observed in eight obese patients (36.36%), and PF and AFI were the variables with highest statistical significance, with p < 0.0001., Conclusion: Ultrasonography is useful tool in the differentiation and quantification of visceral and subcutaneous fat in children. The measures of PF and AFI are useful in the assessment of visceral fat and NAFLD in obese children.

Proper chromosome segregation during cell division is essential for proliferation, and this is facilitated by kinetochores, large protein complexes assembled on the centromeric region of the chromosomes. Although the sequences of centromeric DNA differ totally among organisms, many components of the kinetochores assembled on centromeres are very well conserved among eukaryotes. To define the identity of centromeres, centromere protein A (CENP-A), which is homologous to canonical histone H3, acts as a landmark for kinetochore assembly. Kinetochores mediate spindle–microtubule attachment and control the movement of chromosomes during mitosis and meiosis. To conduct faithful chromosome segregation, kinetochore assembly and microtubule attachment are elaborately regulated. Here we review the current understanding of the composition, assembly, functions and regulation of kinetochores revealed mainly through studies on fission and budding yeasts. Moreover, because recent cumulative evidence suggests the importance of the regulation of the orientation of kinetochore–microtubule attachment, which differs distinctly between mitosis and meiosis, we focus especially on the molecular mechanisms underlying this regulation.

Nucleosomes containing the specific histone H3 variant CENP-A mark the centromere locus on each chromatin and initiate kinetochore assembly. For the common type of regional centromeres, little is known in molecular detail of centromeric chromatin organization, its propagation through cell division, and how distinct organization patterns may facilitate kinetochore assembly. Here, we show that in the fission yeast S. pombe, a relatively small number of CENP-A/Cnp1 nucleosomes are found within the centromeric core and that their positioning relative to underlying DNA varies among genetically homogenous cells. Consistent with the flexible positioning of Cnp1 nucleosomes, a large portion of the endogenous centromere is dispensable for its essential activity in mediating chromosome segregation. We present biochemical evidence that Cnp1 occupancy directly correlates with silencing of the underlying reporter genes. Furthermore, using a newly developed pedigree analysis assay, we demonstrated the epigenetic inheritance of Cnp1 positioning and quantified the rate of occasional repositioning of Cnp1 nucleosomes throughout cell generations. Together, our results reveal the plasticity and the epigenetically inheritable nature of centromeric chromatin organization.