RPA interacts with Rad52 to promote meiotic crossover and noncrossover recombination.

Meiotic recombination is initiated by programmed double-strand breaks (DSBs). Studies in Saccharomyces cerevisiae have shown that, following rapid resection to generate 3' single-stranded DNA (ssDNA) tails, one DSB end engages a homolog partner chromatid and is extended by DNA synthesis, whereas the other end remains associated with its sister. Then, after regulated differentiation into crossover- and noncrossover-fated types, the second DSB end participates in the reaction by strand annealing with the extended first end, along both pathways. This second-end capture is dependent on Rad52, presumably via its known capacity to anneal two ssDNAs. Here, using physical analysis of DNA recombination, we demonstrate that this process is dependent on direct interaction of Rad52 with the ssDNA binding protein, replication protein A (RPA). Furthermore, the absence of this Rad52-RPA joint activity results in a cytologically-prominent RPA spike, which emerges from the homolog axes at sites of crossovers during the pachytene stage of the meiotic prophase. Our findings suggest that this spike represents the DSB end of a broken chromatid caused by either the displaced leading DSB end or the second DSB end, which has been unable to engage with the partner homolog-associated ssDNA. These and other results imply a close correspondence between Rad52-RPA roles in meiotic recombination and mitotic DSB repair.

The synaptonemal complex central region modulates crossover pathways and feedback control of meiotic double-strand break formation.

The synaptonemal complex (SC) is a proteinaceous structure that mediates homolog engagement and genetic recombination during meiosis. In budding yeast, Zip-Mer-Msh (ZMM) proteins promote crossover (CO) formation and initiate SC formation. During SC elongation, the SUMOylated SC component Ecm11 and the Ecm11-interacting protein Gmc2 facilitate the polymerization of Zip1, an SC central region component. Through physical recombination, cytological, and genetic analyses, we found that ecm11 and gmc2 mutants exhibit chromosome-specific defects in meiotic recombination. CO frequencies on a short chromosome (chromosome III) were reduced, whereas CO and non-crossover frequencies on a long chromosome (chromosome VII) were elevated. Further, in ecm11 and gmc2 mutants, more double-strand breaks (DSBs) were formed on a long chromosome during late prophase I, implying that the Ecm11-Gmc2 (EG) complex is involved in the homeostatic regulation of DSB formation. The EG complex may participate in joint molecule (JM) processing and/or double-Holliday junction resolution for ZMM-dependent CO-designated recombination. Absence of the EG complex ameliorated the JM-processing defect in zmm mutants, suggesting a role for the EG complex in suppressing ZMM-independent recombination. Our results suggest that the SC central region functions as a compartment for sequestering recombination-associated proteins to regulate meiosis specificity during recombination.

Rad61/Wpl1 (Wapl), a cohesin regulator, controls chromosome compaction during meiosis.

Meiosis-specific cohesin, required for the linking of the sister chromatids, plays a critical role in various chromosomal events during meiotic prophase I, such as chromosome morphogenesis and dynamics, as well as recombination. Rad61/Wpl1 (Wapl in other organisms) negatively regulates cohesin functions. In this study, we show that meiotic chromosome axes are shortened in the budding yeast rad61/wpl1 mutant, suggesting that Rad61/Wpl1 negatively regulates chromosome axis compaction. Rad61/Wpl1 is required for efficient resolution of telomere clustering during meiosis I, indicating a positive effect of Rad61/Wpl1 on the cohesin function required for telomere dynamics. Additionally, we demonstrate distinct activities of Rad61/Wpl1 during the meiotic recombination, including its effects on the efficient processing of intermediates. Thus, Rad61/Wpl1 both positively and negatively regulates various cohesin-mediated chromosomal processes during meiosis.

Meiotic prophase roles of Rec8 in crossover recombination and chromosome structure.

Rec8 is a prominent component of the meiotic prophase chromosome axis that mediates sister chromatid cohesion, homologous recombination and chromosome synapsis. Here, we explore the prophase roles of Rec8. (i) During the meiotic divisions, Rec8 phosphorylation mediates its separase-mediated cleavage. We show here that such cleavage plays no detectable role for chromosomal events of prophase. (ii) We have analyzed in detail three rec8 phospho-mutants, with 6, 24 or 29 alanine substitutions. A distinct 'separation of function' phenotype is revealed. In the mutants, axis formation and recombination initiation are normal, as is non-crossover recombination; in contrast, crossover (CO)-related events are defective. Moreover, the severities of these defects increase coordinately with the number of substitution mutations, consistent with the possibility that global phosphorylation of Rec8 is important for these effects. (iii) We have analyzed the roles of three kinases that phosphorylate Rec8 during prophase. Timed inhibition of Dbf4-dependent Cdc7 kinase confers defects concordant with rec8 phospho-mutant phenotypes. Inhibition of Hrr25 or Cdc5/polo-like kinase does not. Our results suggest that Rec8's prophase function, independently of cohesin cleavage, contributes to CO-specific events in conjunction with the maintenance of homolog bias at the leptotene/zygotene transition of meiotic prophase.

The association between mental health, chronic disease and sleep duration in Koreans: a cross-sectional study.

BACKGROUND: Sleep duration holds considerable importance as an indicator of mental/physical health. The objective of this study was to investigate the association between sleep duration, mental health, and chronic disease prevalence in Koreans. METHODS: Of 31,596 subjects eligible for the Korean National Health and Nutrition Examination Survey V (2010-2012), 17,638 participants who answered items on sleep duration (aged ≥ 19 yrs) were analyzed in a cross-sectional study. Association between sleep duration, mental health, and chronic disease prevalence was assessed using logistic regression, and adjusted for various socioeconomic and lifestyle characteristics. RESULTS: Short or long sleep duration showed correlations with mental health, and items of significance showed gender-specific patterns. Women displayed significant associations with stress and depressive symptoms, and men with stress, thoughts of suicide, and psychiatric counseling. While stress was related with short sleep duration in both genders, depressive symptoms showed a relationship with long duration in men, and short duration in women. Prevalence of any chronic disease was associated with ≤ 6 h sleep when adjusted for factors including mental health, and among chronic diseases, cancer and osteoarthritis showed associations with short sleep duration, while diabetes and dyslipidemia were associated with normal sleep duration. CONCLUSIONS: Mental health problems were associated with sleep duration with gender-specific patterns. Associations with osteoarthritis, cancer, diabetes, dyslipidemia and abnormal sleep duration persisted after adjustment for mental health.

Kinematic Model-Based Pedestrian Dead Reckoning for Heading Correction and Lower Body Motion Tracking.

In this paper, we present a method for finding the enhanced heading and position of pedestrians by fusing the Zero velocity UPdaTe (ZUPT)-based pedestrian dead reckoning (PDR) and the kinematic constraints of the lower human body. ZUPT is a well known algorithm for PDR, and provides a sufficiently accurate position solution for short term periods, but it cannot guarantee a stable and reliable heading because it suffers from magnetic disturbance in determining heading angles, which degrades the overall position accuracy as time passes. The basic idea of the proposed algorithm is integrating the left and right foot positions obtained by ZUPTs with the heading and position information from an IMU mounted on the waist. To integrate this information, a kinematic model of the lower human body, which is calculated by using orientation sensors mounted on both thighs and calves, is adopted. We note that the position of the left and right feet cannot be apart because of the kinematic constraints of the body, so the kinematic model generates new measurements for the waist position. The Extended Kalman Filter (EKF) on the waist data that estimates and corrects error states uses these measurements and magnetic heading measurements, which enhances the heading accuracy. The updated position information is fed into the foot mounted sensors, and reupdate processes are performed to correct the position error of each foot. The proposed update-reupdate technique consequently ensures improved observability of error states and position accuracy. Moreover, the proposed method provides all the information about the lower human body, so that it can be applied more effectively to motion tracking. The effectiveness of the proposed algorithm is verified via experimental results, which show that a 1.25% Return Position Error (RPE) with respect to walking distance is achieved.

Bone grafting for periprosthetic bone cysts following total ankle arthroplasty.

Aims: The purpose of this study was to assess the success rate and functional outcomes of bone grafting for periprosthetic bone cysts following total ankle arthroplasty (TAA). Additionally, we evaluated the rate of graft incorporation and identified associated predisposing factors using CT scan. Methods: We reviewed a total of 37 ankles (34 patients) that had undergone bone grafting for periprosthetic bone cysts. A CT scan was performed one year after bone grafting to check the status of graft incorporation. For accurate analysis of cyst volumes and their postoperative changes, 3D-reconstructed CT scan processed with 3D software was used. For functional outcomes, variables such as the Ankle Osteoarthritis Scale score and the visual analogue scale for pain were measured. Results: Out of 37 ankles, graft incorporation was successful in 30 cases. Among the remaining seven cases, four (10.8%) exhibited cyst re-progression, so secondary bone grafting was needed. After secondary bone grafting, no further progression has been noted, resulting in an overall 91.9% success rate (34 of 37) at a mean follow-up period of 47.5 months (24 to 120). The remaining three cases (8.1%) showed implant loosening, so tibiotalocalcaneal arthrodesis was performed. Functional outcomes were also improved after bone grafting in all variables at the latest follow-up (p < 0.05). The mean incorporation rate of the grafts according to the location of the cysts was 84.8% (55.2% to 96.1%) at the medial malleolus, 65.1% (27.6% to 97.1%) at the tibia, and 81.2% (42.8% to 98.7%) at the talus. Smoking was identified as a significant predisposing factor adversely affecting graft incorporation (p = 0.001). Conclusion: Bone grafting for periprosthetic bone cysts following primary TAA is a reliable procedure with a satisfactory success rate and functional outcomes. Regular follow-up, including CT scan, is important for the detection of cyst re-progression to prevent implant loosening after bone grafting.

Surgical Excision for Refractory Ischiogluteal Bursitis: A Consecutive Case Series of 21 Patients.

Purpose: A response to conservative treatment is usually obtained in cases of ischiogluteal bursitis. However, the time required to achieve relief of symptoms can vary from days to weeks, and there is a high recurrence rate, thus invasive treatment in addition to conservative treatment can occasionally be effective. Therefore, the aim of this study was to examine surgical excision in cases of refractory ischiogluteal bursitis and to evaluate patients' progression and outcome. Materials and Methods: A review of 21 patients who underwent surgical excision for treatment of ischiogluteal bursitis between February 2009 and July 2020 was conducted. Of these patients, seven patients were male, and 14 patients were female. Injection of steroid and local anesthetic into the ischial bursa was administered at outpatient clinics in all patients, who and they were refractory to conservative treatment, including aspiration and prescription drugs. Therefore, surgery was considered necessary. Excisions were performed by two orthopedic specialists using a direct vertical incision on the ischial area. A review of each patient was performed after excision, and quantification of the outcomes recorded using clinical scoring systems was performed. Results: The results of radiologic evaluation showed that the mean lesion size was 6.2 cm×4.5 cm×3.6 cm. The average disease course after excision was 21.6 days (range, 15-48 days). Measurement of clinical scores, including the visual analog scale and Harris hip scores, was performed during periodic visits, with scores of 0.7 (range, 0-2) and 98.1 (range, 96-100) at one postoperative month, respectively. Conclusion: Surgical excision, with an expectation of favorable results, could be considered for treatment of ischiogluteal bursitis that is refractory to therapeutic injections, aspirations, and medical prescriptions, particularly in moderate-to-severe cases.

Aborted myocardial infarction: evaluation of changes in area at risk, late gadolinium enhancement, and perfusion over time and comparison with overt myocardial infarction.

OBJECTIVE: The objective of our study was to analyze comprehensive MRI findings of aborted myocardial infarction (MI) in terms of the area at risk, late enhancement, and perfusion on initial and follow-up studies compared with overt MI. SUBJECTS AND METHODS: Eleven cases of aborted MI and 18 cases of overt MI were included in this study. We evaluated the location and signal pattern of infarction on both T2-weighted imaging and delayed enhancement MRI. For quantitative analysis, we calculated the size and contrast ratio of the myocardial signal abnormality compared with remote myocardium on T2-weighted imaging and delayed enhancement MRI. We also evaluated the regional systolic function on cine MRI and the perfusion abnormality on first-pass perfusion MRI. Six months after initial imaging, MRI was repeated to see changes in enhancement pattern and functional indexes. RESULTS: T2-weighted images of all patients showed homogeneous high signal intensity (SI) along the vascular territory of the culprit lesion. MRI of patients with aborted MI showed no (n = 5) or minimal (n = 6) delayed enhancement. Compared with overt MI cases, aborted MI cases also were significantly smaller (p = 0.001) and showed significantly lower SI (p = 0.002) of the enhancing region on delayed enhancement MRI. On follow-up delayed enhancement MRI, the enhancing region was smaller in most cases. All aborted MI cases except one showed hypokinesia and a perfusion defect at the corresponding vascular territory on the initial MRI, but these abnormal findings had normalized on follow-up MRI. CONCLUSION: The characteristic MRI findings of aborted MI are the absence of or minimal enhancement on delayed enhancement MRI compared with overt MI. On follow-up MRI of aborted MI cases, the area at risk, minimal enhancement, and perfusion defect had normalized.

In-situ neutron diffraction study of lattice deformation behaviour of commercially pure titanium at cryogenic temperature.

Titanium has a significant potential for the cryogenic industrial fields such as aerospace and liquefied gas storage and transportation due to its excellent low temperature properties. To develop and advance the technologies in cryogenic industries, it is required to fully understand the underlying deformation mechanisms of Ti under the extreme cryogenic environment. Here, we report a study of the lattice behaviour in grain families of Grade 2 CP-Ti during in-situ neutron diffraction test in tension at temperatures of 15-298 K. Combined with the neutron diffraction intensity analysis, EBSD measurements revealed that the twinning activity was more active at lower temperature, and the behaviour was complicated with decreasing temperature. The deviation of linearity in the lattice strains was caused by the load-redistribution between plastically soft and hard grain families, resulting in the three-stage hardening behaviour. The lattice strain behaviour further deviated from linearity with decreasing temperature, leading to the transition of plastically soft-to-hard or hard-to-soft characteristic of particular grain families at cryogenic temperature. The improvement of ductility can be attributed to the increased twinning activity and a significant change of lattice deformation behaviour at cryogenic temperature.

Canine hippocampal formation composited into three-dimensional structure using MPRAGE.

This study was performed to anatomically illustrate the living canine hippocampal formation in three-dimensions (3D), and to evaluate its relationship to surrounding brain structures. Three normal beagle dogs were scanned on a MR scanner with inversion recovery segmented 3D gradient echo sequence (known as MP-RAGE: Magnetization Prepared Rapid Gradient Echo). The MRI data was manually segmented and reconstructed into a 3D model using the 3D slicer software tool. From the 3D model, the spatial relationships between hippocampal formation and surrounding structures were evaluated. With the increased spatial resolution and contrast of the MPRAGE, the canine hippocampal formation was easily depicted. The reconstructed 3D image allows easy understanding of the hippocampal contour and demonstrates the structural relationship of the hippocampal formation to surrounding structures in vivo.

Mec1 Modulates Interhomolog Crossover and Interplays with Tel1 at Post Double-Strand Break Stages.

During meiosis I, programmed DNA double-strand breaks (DSBs) occur to promote chromosome pairing and recombination between homologs. In Saccharomyces cerevisiae, Mec1 and Tel1, the orthologs of human ATR and ATM, respectively, regulate events upstream of the cell cycle checkpoint to initiate DNA repair. Tel1ATM and Mec1ATR are required for phosphorylating various meiotic proteins during recombination. This study aimed to investigate the role of Tel1ATM and Mec1ATR in meiotic prophase via physical analysis of recombination. Tel1ATM cooperated with Mec1ATR to mediate DSB-to-single end invasion transition, but negatively regulated DSB formation. Furthermore, Mec1ATR was required for the formation of interhomolog joint molecules from early prophase, thus establishing a recombination partner choice. Moreover, Mec1ATR specifically promoted crossover-fated DSB repair. Together, these results suggest that Tel1ATM and Mec1ATR function redundantly or independently in all post-DSB stages.

Activation of notch signaling in a xenograft model of brain metastasis.

PURPOSE: The potential of metastasis can be predicted from clinical features like tumor size, histologic grade, and gene expression patterns. We examined the whole-genome transcriptomic profile of a xenograft model of breast cancer to understand the characteristics of brain metastasis. EXPERIMENTAL DESIGN: Variants of the MDA-MB-435 cell were established from experimental brain metastases. The LvBr2 variant was isolated from lesions in a mouse injected in the left ventricle of the heart, and these cells were used for two cycles of injection into the internal carotid artery and selection of brain lesions, resulting in the Br4 variant. To characterize the different metastatic variants, we examined the gene expression profile of MDA-MB-435, LvBr2, and Br4 cells using microarrays. RESULTS: We could identify 2,016 differentially expressed genes in Br4 by using the F test. Various metastasis-related genes and a number of genes related to angiogenesis, migration, tumorigenesis, and cell cycle were differentially expressed by the Br4 cells. Notably, the Notch signaling pathway was activated in Br4, with increased Jag2 mRNA, activated Notch intracellular domain, and Notch intracellular domain/CLS promoter-luciferase activity. Br4 cells were more migratory and invasive than MDA-MB-435 cells in collagen and Matrigel Transwell assays, and the migration and invasion of Br4 cells were significantly inhibited by inactivation of Notch signaling using DAPT, a gamma-secretase inhibitor, and RNA interference-mediated knockdown of Jagged 2 and Notch1. CONCLUSIONS: Taken together, these results suggest that we have isolated variants of a human cancer cell line with enhanced brain metastatic properties, and the activation of Notch signaling might play a crucial role in brain metastasis.

Molecular responses of Jurkat T-cells to 1763 MHz radiofrequency radiation.

PURPOSE: The biological effects of exposure to mobile phone emitted radiofrequency (RF) radiation are the subject of intense study, yet the hypothesis that RF exposure is a potential health hazard remains controversial. In this paper, we monitored cellular and molecular changes in Jurkat human T lymphoma cells after irradiating with 1763 MHz RF radiation to understand the effect on RF radiation in immune cells. MATERIALS AND METHODS: Jurkat T-cells were exposed to RF radiation to assess the effects on cell proliferation, cell cycle progression, DNA damage and gene expression. Jurkat cells were exposed to 1763 MHz RF radiation at 10 W/kg specific absorption rate (SAR) and compared to sham exposed cells. RESULTS: RF exposure did not produce significant changes in cell numbers, cell cycle distributions, or levels of DNA damage. In genome-wide analysis of gene expressions, there were no genes changed more than two-fold upon RF-radiation while ten genes change to 1.3 approximately 1.8-fold. Among ten genes, two cytokine receptor genes such as chemokine (C-X-C motif) receptor 3 (CXCR3) and interleukin 1 receptor, type II (IL1R2) were down-regulated upon RF radiation, but they were not directly related to cell proliferation or DNA damage responses. CONCLUSION: These results indicate that the alterations in cell proliferation, cell cycle progression, DNA integrity or global gene expression was not detected upon 1763 MHz RF radiation under 10 W/kg SAR for 24 h to Jurkat T cells.

Characterization of biological effect of 1763 MHz radiofrequency exposure on auditory hair cells.

PURPOSE: Radiofrequency (RF) exposure at the frequency of mobile phones has been reported not to induce cellular damage in in vitro and in vivo models. We chose HEI-OC1 immortalized mouse auditory hair cells to characterize the cellular response to 1763 MHz RF exposure, because auditory cells could be exposed to mobile phone frequencies. MATERIALS AND METHODS: Cells were exposed to 1763 MHz RF at a 20 W/kg specific absorption rate (SAR) in a code division multiple access (CDMA) exposure chamber for 24 and 48 h to check for changes in cell cycle, DNA damage, stress response, and gene expression. RESULTS: Neither of cell cycle changes nor DNA damage was detected in RF-exposed cells. The expression of heat shock proteins (HSP) and the phosphorylation of mitogen-activated protein kinases (MAPK) did not change, either. We tried to identify any alteration in gene expression using microarrays. Using the Applied Biosystems 1700 full genome expression mouse microarray, we found that only 29 genes (0.09% of total genes examined) were changed by more than 1.5-fold on RF exposure. CONCLUSION: From these results, we could not find any evidence of the induction of cellular responses, including cell cycle distribution, DNA damage, stress response and gene expression, after 1763 MHz RF exposure at an SAR of 20 W/kg in HEI-OC1 auditory hair cells.

Relationships of Lower Lung Fibrosis, Pleural Disease, and Lung Mass with Occupational, Household, Neighborhood, and Slate Roof-Dense Area Residential Asbestos Exposure.

This study aimed to evaluate the relationship between various asbestos exposure routes and asbestos-related disorders (ARDs). The study population comprised 11,186 residents of a metropolitan city who lived near asbestos factories, shipyards, or in slate roof-dense areas. ARDs were determined from chest X-rays indicating lower lung fibrosis (LFF), pleural disease (PD), and lung masses (LMs). Of the subjects, 11.2%, 10.4%, 67.2% and 8.3% were exposed to asbestos via occupational, household, neighborhood, and slate roof routes, respectively. The odds ratio (OR) of PD from household exposure (i.e., living with asbestos-producing workers) was 1.9 (95% confidence interval: 0.9⁻4.2), and those of LLF and PD from neighborhood exposure, or residing near asbestos factories) for <19 or >20 years, or near a mine, were 4.1 (2.8⁻5.8) and 4.8 (3.4⁻6.7), 8.3 (5.5⁻12.3) and 8.0 (5.5⁻11.6), and 4.8 (2.7⁻8.5) and 9.0 (5.6⁻14.4), respectively. The ORs of LLF, PD, and LM among those residing in slate-dense areas were 5.5 (3.3⁻9.0), 8.8 (5.6⁻13.8), and 20.5 (10.4⁻40.4), respectively. Substantial proportions of citizens residing in industrialized cities have potentially been exposed to asbestos, and various exposure routes are associated with the development of ARDs. Given the limitations of this study, including potential confounders such as socioeconomic status, further research is needed.

Roles of Budding Yeast Hrr25 in Recombination and Sporulation.

Hrr25, a casein kinase 1 δ/ε homolog in budding yeast, is essential to set up mono-orientation of sister kinetochores during meiosis. Hrr25 kinase activity coordinates sister chromatid cohesion via cohesin phosphorylation. Here, we investigated the prophase role of Hrr25 using the auxin-inducible degron system and by ectopic expression of Hrr25 during yeast meiosis. Hrr25 mediates nuclear division in meiosis I but does not affect DNA replication. We also found that initiation of meiotic double-strand breaks as well as joint molecule formation were normal in HRR25-deficient cells. Thus, Hrr25 is essential for termination of meiotic division but not homologous recombination.

Identification of Angiogenesis Rich-Viable Myocardium using RGD Dimer based SPECT after Myocardial Infarction.

Cardiac healing after myocardial ischemia is a complex biological process. Advances in understanding of wound healing response have paved the way for clinical testing of novel molecular imaging to improve clinical outcomes. A key factor for assessing myocardial viability after ischemic injury is the evaluation of angiogenesis accompanying increased expression of integrin αvß3. Here, we describe the capability of an αvß3 integrin-targeting SPECT agent, (99m)Tc-IDA-D-[c(RGDfK)]2, for identification of ischemic but viable myocardium, i.e., hibernating myocardium which is crucial to predict functional recovery after revascularization, the standard care of cardiovascular medicine. In vivo SPECT imaging of rat models with transient coronary occlusion showed significantly high uptake of (99m)Tc-IDA-D-[c(RGDfK)]2 in the ischemic region. Comparative measurements with (201)Tl SPECT and (18)F-FDG PET, then, proved that such prominent uptake of (99m)Tc-IDA-D-[c(RGDfK)]2 exactly matched the hallmark of hibernation, i.e., the perfusion-metabolism mismatch pattern. The uptake of (99m)Tc-IDA-D-[c(RGDfK)]2 was non-inferior to that of (18)F-FDG, confirmed by time-course variation analysis. Immunohistochemical characterization revealed that an intense signal of (99m)Tc-IDA-D-[c(RGDfK)]2 corresponded to the vibrant angiogenic events with elevated expression of αvß3 integrin. Together, these results establish that (99m)Tc-IDA-D-[c(RGDfK)]2 SPECT can serve as a sensitive clinical measure for myocardial salvage to identify the patients who might benefit most from revascularization.

Mitotic cohesin subunit Mcd1 regulates the progression of meiotic recombination in budding yeast.

The cohesin complex holds sister chromatids together and prevents premature chromosome segregation until the onset of anaphase. Mcd1 (also known as Scc1), the α-kleisin subunit of cohesin, is a key regulatory subunit of the mitotic cohesin complex and is required for maintaining sister chromatid cohesion, chromosome organization, and DNA repair. We investigated the function of Mcd1 in meiosis by ectopically expressing Mcd1 during early meiotic prophase I in Saccharomyces cerevisiae. Mcd1 partially regulated the progression of meiotic recombination, sister chromatid separation, and nuclear division. DNA physical analysis during meiotic recombination showed that Mcd1 induced double-strand breaks (DSBs) but negatively regulated homologous recombination during DSB repair; Mcd1 expression delayed post-DSB stages, leading to inefficiencies in the DSB-to-joint molecule (JM) transition and subsequent crossover formation. These findings indicate that meiotic cells undergo Mcd1-mediated DSB formation during prophase I, and that residual Mcd1 could regulate the progression of JM formation during meiotic recombination.

Sodium [¹8F]fluoride PET/CT in myocardial infarction.

PURPOSE: Sodium [(18)F]fluoride (Na[(18)F]F) positron emission tomography with integrated computed tomography (PET/CT) has not been used for imaging myocardial infarction (MI). Here, we aimed to investigate the Na[(18)F]F PET/CT features of MI in a rat model. PROCEDURES: MI was induced by coronary artery ligation in 8-week-old male Spraque-Dawley rats (300 ± 10 g) and confirmed by triphenyl tetrazolium chloride (TTC) staining. Na[(18)F]F PET/CT images were obtained using an animal-dedicated PET/CT scanner (NanoPET/CT, Mediso) in vivo and ex vivo. Uptake of Na[(18)F]F was quantitated using the standardized uptake value (SUV). Myocardial apoptosis was evaluated using histone-1 targeted peptide (ApoPep-1) and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining, while calcium accumulation was investigated using von Kossa's staining. Na[(18)F]F PET/CT was compared with (99m)Tc-methoxyisobutylisonitrile (MIBI) or (99m)Tc-hydroxymethylenediphosphonate (HMDP) single photon emission computed tomography/computed tomography (SPECT/CT) in rats with day 1 MI. RESULTS: The rats showed strong Na[(18)F]F uptake both in vivo and ex vivo; the maximal uptake occurred 1 day after MI (SUV ratio of infarct to lung = 4.56 ± 0.74, n = 7, P = 0.0183 vs the control). The Na[(18)F]F uptake area perfectly matched the apoptotic area, determined by ApoPep-1 uptake and TUNEL assay. However, calcification, assessed by von Kossa's staining, was absent in the infarct. Na[(18)F]F PET/CT showed an increased uptake at the perfusion deficit area in [(99m)Tc]MIBI SPECT/CT and an equivalent signal to [(99m)Tc]HMDP SPECT/CT in rats with day 1 MI. CONCLUSIONS: Na[(18)F]F PET/CT is a promising hot-spot imaging modality for MI.