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Abstract DNA-loop extrusion is considered to be a universal principle of structural maintenance of chromosome (SMC) proteins with regard to chromosome organization. Despite recent advancements in structural dynamics studies that involve the use of cryogenic-electron microscopy (Cryo-EM), atomic force microscopy (AFM), etc., the precise molecular mechanism underlying DNA-loop extrusion by SMC proteins remains the subject of ongoing discussions. In this context, we propose a scrunching model that incorporates the anisotropic motion of SMC folding with a baton-pass mechanism, offering a potential explanation of how a “DNA baton” is transferred from the hinge domain to a DNA pocket via an anisotropic hinge motion. This proposed model provides insights into how SMC proteins unidirectionally extrude DNA loops in the direction of loop elongation while also maintaining the stability of a DNA loop throughout the dynamic process of DNA-loop extrusion.

Abstract Chromosomal phase separation is involved in a broad spectrum of chromosome organization and functional processes. Nonetheless, the intricacy of this process has left its molecular mechanism unclear. Here, we introduce the principles governing phase separation and its connections to physiological roles in this context. Our primary focus is contrasting two phase separation mechanisms: self-association-induced phase separation (SIPS) and bridging-induced phase separation (BIPS). We provide a comprehensive discussion of the distinct features characterizing these mechanisms and offer illustrative examples that suggest their broad applicability. With a detailed understanding of these mechanisms, we explore their associations with nucleosomes and chromosomal biological functions. This comprehensive review contributes to the exploration of uncharted territory in the intricate interplay between chromosome architecture and function.

Background: Early-stage lung cancers detected by low-dose computed tomography (CT) often require confirmation through invasive procedures due to the absence of endobronchial lesions. This study assesses the diagnostic utility of bronchial washing fluid (BW) sequencing, a less invasive alternative, aiming to identify patient characteristics most suited for this approach. Methods: From June 2017 to March 2018, we conducted a prospective cohort study by enrolling patients with incidental lung lesions suspected of early-stage lung cancer at two independent hospitals, and 114 were diagnosed with lung cancer while 50 were diagnosed with benign lesions. BW sequencing was performed using a targeted gene panel, and the clinical characteristics of patients detected with cancer through sequencing were identified. Results: Malignant cells were detected in 33 patients (28.9 %) through BW cytology. By applying specificity-focused mutation criteria, BW sequencing classified 42 patients (36.8 %) as having cancer. Among the cancer patients who were BW sequencing positive and BW cytology negative, 15 patients (75.0 %) showed necrosis on CT. The sensitivity of BW sequencing was particularly enhanced in patients with necrotic tumors, reaching 75 %. Conclusions: BW sequencing presents a viable, non-invasive diagnostic option for early-stage lung cancer, especially valuable in patients with necrotic lesions. By potentially reducing the reliance on more invasive diagnostic procedures, this method could streamline clinical workflows, decrease patient burden, and improve overall diagnostic efficiency.

Objectives: The objective of this study was to identify factors associated with adolescent obesity, as well as any new factors that correlated with a change in the rate of obesity over time. Methods: The study used 5-yearly data collected by the Korea Youth Risk Behavior Survey starting from the year 2006 up until 2021 (data from 2nd, 7th, 11th, and 17th surveys were analyzed). Factors such as demographics, dietary factors, health behavioral factors, and mental health factors were studied. All data were analyzed using IBM SPSS 27.0, employing chi-square tests and multiple logistic regression analysis. Results: This study included data from a total of 255,200 participants. Factors contributing to obesity varied with time. Over the survey duration of 15 years, low academic achievement, parents with low levels of education, low frequency of fruit consumption, low frequency of fast food intake, long periods of being seated, and high levels of stress were significantly associated with a high rate of obesity. Factors that showed a new correlation with an increase in obesity rates included living with single parents, low frequency of muscle strengthening exercises, and experiencing intense sadness and despair in the past year. Factors that were correlated with a change in obesity rates over time included household economic status, frequency of carbonated beverage consumption, frequency of intense physical activity, and frequency of alcohol consumption. Breakfast intake and smoking were not significantly associated with obesity rates in the 15-year period. Conclusions: While several factors associated with obesity remained consistent over time, several new factors have emerged in response to social, economic, and environmental changes contributed to a change in obesity rate over time. Therefore, to prevent and manage adolescent obesity, continuous research into the new emergent factors contributing to obesity is needed.

Abstract Current guidelines recommend that cytotoxic chemotherapy be considered first in non-small cell lung cancer (NSCLC) patients with multiple metastases, and whole-brain radiotherapy (WBRT) is not initially recommended even if brain metastases are present. However, cytotoxic chemotherapeutic agents are less effective in brain metastases due to poor blood–brain barrier permeability. We investigated the effect of WBRT in combination with cytotoxic chemotherapy on survival in NSCLC patients who were EGFR, ALK, and PD-L1 negative, had an ECOG PS of 2, and had multiple metastases including brain metastases. From January 2005 to December 2018, histologically confirmed NSCLC patients who were EGFR, ALK, and PD-L1 negative, had an ECOG PS of 2, and had multiple metastases including brain metastases were included in this study. Patients were classified into two groups based on receiving WBRT prior to or concurrently with administration of first-line chemotherapeutic agents or receiving chemotherapy only. We compared intracranial progression-free survival (iPFS) and overall survival (OS). Of the 240 NSCLC patients with brain metastases at diagnosis and an ECOG PS of 2, 67 patients were EGFR, ALK, and PD-L1 negative with multiple metastases including brain metastases. Among those patients, 43 (64.2%) received WBRT prior to or concurrently with platinum-based chemotherapy. Patients who received WBRT prior to or concurrently with chemotherapy had better iPFS (7.7 months [4.8–10.6] vs. 3.5 months [2.1–4.9], p = 0.009) and OS (10.8 months [5.9–15.7] vs. 6.1 months [1.9–10.3], p = 0.038) than those who did not receive WBRT. In multivariate analyses, WBRT was significantly associated with iPFS (HR: 1.94 and 95% CI 1.11–3.40, p = 0.020) and OS (HR: 1.92 and 95% CI 1.08–3.42, p = 0.027). In NSCLC patients who are EGFR, ALK, and PD-L1 negative, have an ECOG PS of 2, and have multiple metastases including brain metastases, WBRT prior to or concurrently with chemotherapy could improve iPFS and OS. Therefore, the combination of WBRT with cytotoxic chemotherapy should be considered in these patients.

Objectives: This study examines the status of iodine intake and compares the characteristics (region and thyroid disease prevalence) according to the iodine-sourced food intake pattern in Chinese adults. Methods: An online survey was conducted by enrolling 437 Chinese adults aged 18-65 years, living in three regions with different iodine nutritional statuses: Sichuan, Chongqing, and Guangdong. Results: The prevalence of thyroid diseases in Sichuan, Chongqing, and Guangdong were 12.5%, 8.5%, and 2.8%, respectively. Conversely, the proportion of people who received thyroid disease-related examinations was a mere 37.5%. Among the subjects who underwent thyroid examination, the prevalence of thyroid disease in the three regions was 32.2%, 21.8%, and 8.0%, respectively. No differences were obtained in the total iodine intake by region, but the type of iodine source foods differed. Regardless of the region, the highest iodine content was obtained from seaweed. However, the iodine content from iodized salt and other foods differed significantly by region. Factor analysis revealed three food intake patterns according to the iodine food source. The study further determined regional differences and differences in the prevalence of thyroid disease according to food intake patterns. Conclusions: High salt intake can also increase iodine intake, which is thought to have an effect on the occurrence of iodine-excess thyroid disease. Hence, efforts focused on improving salty eating habits need to be implemented.

Background and Objectives: The mechanisms involved in the development of brain metastasis (BM) remain elusive. Here, we investigated whether BM is associated with spine involvement in patients with non-small-cell lung cancer (NSCLC). Materials and Methods: A consecutive 902 patients with metastatic NSCLC were included from the Inha Lung Cancer Cohort. Patients with BM at diagnosis or subsequent BM development were evaluated for both spine involvement in NSCLC and anatomic proximity of BM to the cerebrospinal fluid (CSF) space. Results: At diagnosis, BM was found in 238 patients (26.4%) and bone metastasis was found in 393 patients (43.6%). In patients with bone metastasis, spine involvement was present in 280 patients. BM subsequently developed in 82 (28.9%) of 284 patients without BM at diagnosis. The presence of spine metastasis was associated with BM at diagnosis and subsequent BM development (adjusted odd ratios and 95% confidence intervals = 2.42 and 1.74–3.37, p < 0.001; 1.94 and 1.19–3.18, p = 0.008, respectively). Most patients with spine metastasis, either with BM at diagnosis or subsequent BM, showed BM lesions located adjacent (within 5mm) to the CSF space (93.8% of BM at the diagnosis, 100% of subsequent BM). Conclusions: These findings suggest that the presence of spine involvement is a risk factor for BM development in NSCLC patients with bone metastasis.

Abstract Cholesterol is essential for neuronal activity and function. Cholesterol depletion in the plasma membrane impairs synaptic transmission. However, the molecular mechanisms by which cholesterol deficiency leads to defects in vesicle fusion remain poorly understood. Here, it is shown that cholesterol is required for Ca2+‐dependent native vesicle fusion using the in vitro reconstitution of fusion and amperometry to monitor exocytosis in chromaffin cells. Purified native vesicles are crucial for the reconstitution of physiological Ca2+‐dependent fusion, because vesicle‐mimicking liposomes fail to reproduce the cholesterol effect. Intriguingly, cholesterol has no effect on the membrane binding of synaptotagmin‐1, a Ca2+ sensor for ultrafast fusion. Cholesterol strengthens local membrane deformation and bending induced by synaptotagmin‐1, thereby lowering the energy barrier for Ca2+‐dependent fusion to occur. The data provide evidence that cholesterol depletion abolishes Ca2+‐dependent vesicle fusion by disrupting synaptotagmin‐1‐induced membrane bending, and suggests that cholesterol is an essential lipid regulator for Ca2+‐dependent fusion.

Abstract Background A heterogeneous radiological response is frequently observed in cancer patients and could reflect tumor heterogeneity. We investigated the prognostic impact of heterogeneous radiological responses in patients with advanced non‐small‐cell lung cancer (NSCLC) who received platinum‐based chemotherapy. Methods The treatment response according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria was evaluated in 212 patients with advanced NSCLC who received platinum‐based chemotherapy. Patients with partial response (PR) or stable disease (SD) were classified into “PR homo,” “PR hetero,” “SD homo,” and “SD hetero” by the presence of a heterogeneous radiological response, and survival was compared between groups. We also compared survival based on the presence of metabolic responses in lesions with heterogeneous radiological responses. Results Fifty‐two patients (24.5%) were classified as PR, 112 patients (52.8%) as SD, and 48 patients (22.7%) as progressive disease (PD). There was no significant difference in progression‐free survival (PFS) and overall survival (OS) between the PR homo and PR hetero groups. The SD homo group had a longer PFS and OS than the SD hetero group. In the SD hetero group, patients with increased maximum standardized uptake value (SUVmax) in lesions with heterogeneous radiological responses had a shorter PFS than those with a stable SUVmax. Conclusions The presence of lesions with radiological heterogeneity was associated with disease progression and poor prognosis in the SD group. Patients with heterogeneous radiological responses require careful monitoring.

Crizotinib is an oral selective small-molecular tyrosine kinase inhibitor (TKI) that suppress the activity of anaplastic lymphoma kinase (ALK) and ROS1 kinases, as well as mesenchymal-epithelial transition. The cumulative clinical trials in patients with advanced ALK- or ROS1-rearrangement NSCLC indicate that crizotinib has significant antitumor activity and a tolerable safety profile, with mild or moderate adverse events of visual disorders, diarrhea, nausea, and vomiting. As with other TKIs, however, the occurrence of crizotinib-related interstitial lung disease (crizotinib-ILD) remains a major clinical dilemma that can lead to the permanent discontinuation of TKI during cancer treatment. When there is no suitable alternative therapy for patients who develop crizotinib-ILD, some clinicians have reported successful crizotinib retreatment in cases of ALK-rearrangement NSCLC. Unfortunately, there are no specific guidelines for the treatment or retreatment of TKI-related ILD. We herein report the first successful crizotinib retreatment after crizotinib-ILD in a patient with ROS1-rearranged NSCLC, and suggest a retreatment strategy after crizotinib-ILD based on a literature review.

Fueled by ATP hydrolysis in N-ethylmaleimide sensitive factor (NSF), the 20S complex disassembles SNARE complexes in a single unravelling step. Here authors use single-molecule methods to show cooperativity between the NSF and SNARE complex, which prevents ATP consumption without productive disassembly.

Abstract Using either 24-2 or 10-2 visual field (VF) testing only is not enough to cover all the various types of glaucomatous VF defects. We investigated the performance of the combined 24-2 and 10-2 perimetry when conducted together and separately using the structure–function relationship. A total of 30 glaucoma patients with isolated peripheral nasal step, 37 patients with isolated paracentral scotoma, and 38 patients with both paracentral and nasal scotoma were included. To create the combined Humphrey VF test, a custom test pattern was established using the built-in custom point options, an example of the X, Y coordinate system. In glaucoma patients with peripheral nasal step, the superotemporal topographic structure–function relationship with peripapillary retinal nerve fiber layer (RNFL) thickness was superior in relation to the combined or 24-2 perimetry relative to the 10-2 perimetry (both P

The major sites of metastasis in non-small cell lung cancer (NSCLC) are bones, the brain, adrenal glands, the liver, the contralateral lung, and distant lymph nodes. Solitary metastasis in an uncommon site is very rare; therefore, it has not often been reported. Identifying whether a solitary lesion is a metastatic lesion is important because it decisively influences the stage and treatment decisions. We report a series of cases of NSCLC diagnosis with uncommon solitary metastasis. (1) A 71-year-old man was diagnosed with poorly differentiated NSCLC after a bronchoscopic biopsy of a tumor in the bronchus of the right middle lobe. A hypermetabolic lesion was observed in the tail of the pancreas using positron emission tomography/computed tomography (PET/CT), and metastasis of NSCLC was confirmed using endoscopic ultrasound fine-needle aspiration (EUS-FNA). (2) A 77-year-old man was diagnosed with squamous cell carcinoma after a bronchoscopic biopsy of a tumor in the bronchus of the left upper lobe. A hypermetabolic lesion was observed in the bilateral lobes of the thyroid gland using PET/CT, and metastasis of the squamous cell carcinoma was confirmed by FNA and cytology. (3) A 79-year-old woman was diagnosed with adenocarcinoma by brushing cytology performed on the apicoposterior segmental bronchus of the left upper lobe. Hypermetabolic lesions were observed using PET/CT in the subcutaneous layer of the right back and the left breast, and metastases of adenocarcinoma were confirmed by biopsies in each lesion. These three patients were treated with platinum-based chemotherapy for stage IV lung cancer. With this case series, we recommend that, when a solitary lesion is observed in NSCLC patients, a tissue biopsy should be performed, even if the lesion is located in an organ where lung cancer metastasis is uncommon.

Circulating tumor DNA (ctDNA) has been utilized to monitor the clinical course of patients of non-small-cell lung cancer (NSCLC) who receive therapies targeting druggable mutations. However, despite providing valuable information on how NSCLC would naturally progress, the clinical utility of ctDNA for clinical-course monitoring and prediction of treatment-naïve NSCLC patients without druggable mutations remain unknown. We longitudinally followed a total of 12 treatment-naïve NSCLC patients, who did not harbor EGFR and ALK mutations, by collecting clinical information, radiological data, and plasma samples. Changes in ctDNA levels and tumor burden (TB) were compared with each other. New metastasis development, volume doubling time (VDT), and overall survival (OS) were analyzed regarding ctDNA detection at diagnosis. ctDNA was detected in the plasma of seven (58.3%) patients. Changes in ctDNA levels correlated with those in TB in a substantial fraction (57.1%) of patients and was also associated with brain metastasis, tumor necrosis, or pneumonia in other patients. All patients with ctDNA detection developed new metastasis during follow-ups in the organs that had been devoid of metastasis at diagnosis. The patients without ctDNA detection did not develop new metastasis (median duration of follow-ups: 9.8 months). In addition, patients with ctDNA detection had shorter VDT (p = 0.039) and worse OS (p = 0.019) than those without ctDNA detection. The natural course of NSCLC progression can be monitored by measuring ctDNA levels. Detection of ctDNA at diagnosis can predict development of new metastasis, rapid tumor growth and poor survival of NSCLC patients.

Abstract CD47 (integrin-associated protein), a multi-spanning transmembrane protein expressed in all cells including red blood cells (RBCs) and leukocytes, interacts with signal regulatory protein α (SIRPα) on macrophages and thereby inhibits phagocytosis of RBCs. Recently, we generated a novel C57BL/6J CD47 knockout (CD47-/- hereafter) mouse line by employing a CRISPR/Cas9 system at Center for Mouse Models of Human Disease, and here report their hematological phenotypes. On monitoring their birth and development, CD47-/- mice were born viable with a natural male-to-female sex ratio and normally developed from birth through puberty to adulthood without noticeable changes in growth, food/water intake compared to their age and sex-matched wild-type littermates up to 26 weeks. Hematological analysis revealed a mild but significant reduction of RBC counts and hemoglobin in 16 week-old male CD47-/- mice which were aggravated at the age of 26 weeks with increased reticulocyte counts and mean corpuscular volume (MCV), suggesting hemolytic anemia. Interestingly, anemia in female CD47-/- mice became evident at 26 weeks, but splenomegaly was identified in both genders of CD47-/- mice from the age of 16 weeks, consistent with development of hemolytic anemia. Additionally, helper and cytotoxic T cell populations were considerably reduced in the spleen, but not in thymus, of CD47-/- mice, suggesting a crucial role of CD47 in proliferation of T cells. Collectively, these findings indicate that our CD47-/- mice have progressive hemolytic anemia and splenic depletion of mature T cell populations and therefore may be useful as an in vivo model to study the function of CD47.

Abstract Recombination activating gene-2 (RAG-2) plays a crucial role in the development of lymphocytes by mediating recombination of T cell receptors and immunoglobulins, and loss of RAG-2 causes severe combined immunodeficiency (SCID) in humans. Rag-2 knockout mice created using homologous recombination in ES cells have served as a valuable immunodeficient platform, but concerns have persisted on the specificity of Rag-2-related phenotypes in these animals due to the limitations associated with the genome engineering method used. To precisely investigate the function of Rag-2, we recently established a new Rag-2 knockout FVB mouse line (Rag-2-/-) manifesting lymphopenia by employing a CRISPR/Cas9 system at Center for Mouse Models of Human Disease. In this study, we further characterized their phenotypes focusing on histopathological analysis of lymphoid organs. Rag-2-/- mice showed no abnormality in development compared to their WT littermates for 26 weeks. At necropsy, gross examination revealed significantly smaller spleens and thymuses in Rag-2-/- mice, while histopathological investigation revealed hypoplastic white pulps with intact red pulps in the spleen, severe atrophy of the thymic cortex and disappearance of follicles in lymph nodes. However, no perceivable change was observed in the bone marrow. Moreover, our analyses showed a specific reduction of lymphocytes with a complete loss of mature T cells and B cells in the lymphoid organs, while natural killer cells and splenic megakaryocytes were increased in Rag-2-/- mice. These findings indicate that our Rag-2-/- mice show systemic lymphopenia with the relevant histopathological changes in the lymphoid organs, suggesting them as an improved Rag-2-related immunodeficient model.

Introduction Sonography and magnetic resonance imaging (MRI) may be helpful to obtain an accurate diagnosis of acute abdominal pain in pregnancy. Adnexal torsion presenting in the first or second trimester can be confirmed and treated through laparoscopic surgery; however laparoscopic surgery in the third trimester can be difficult owing to the large uterus, and a gridiron incision can be useful. Case Report/Case presentation An 18-year-old gravida 1, para 0 (G1P0) woman at 30 + 4 weeks of gestation presented with sudden-onset cyclic pain in the right lower quadrant. Abdominal ultrasonography showed a normal appendix, and MRI showed a normal appendix and normal ovaries. The patient’s prominent tender point was marked and compared with the MR images, which confirmed the mark as the position of the right ovary. Laparotomy was performed through a gridiron incision, and a folded right ovary was identified. The ovary was unfolded, and TachoSil® and Surgicel® were used to maintain the unfolded position. The patient’s pain resolved, and her postoperative course was uneventful. She delivered a healthy, 2540-g male baby at 35 weeks’ gestation. Discussion/Conclusions A gridiron incision was useful to treat a folded ovary in the third trimester and to evaluate the adnexa and minimize uterine manipulation.

Abstract Background Electrospun fibrous matrices are of great importance for tissue engineering and drug delivery device. However, relatively low mechanical strength of the fibrous matrix is one of the major disadvantages. NDs with a positive charge were selected to enhance the mechanical property of a composited fibrous matrix by inducing the intermolecular interaction between NDs and polymer chain. We prepared ND-composited poly (ε-caprolactone) (PCL) fibrous matrices by electrospinning and evaluated their performance in terms of mechanical strength and cell behaviors. Methods A predetermined amounts of NDs (0.5, 1, 2 and 3 wt%) were added into PCL solution in a mixture of chloroform and 2,2,2-trifluoroethanol (8:2). ND-composited PCL (ND/PCL) fibrous matrices were prepared by electrospinning method. The tensile properties of the ND/PCL fibrous matrices were analyzed by using a universal testing machine. Mouse calvaria-derived preosteoblast (MC3T3-E1) was used for cell proliferation, alkaline phosphatase (ALP) assay, and Alizarin Red S staining. Results The diameters of the fibrous matrices were adjusted to approximately 1.8 μm by changing process variables. The intermolecular interaction between NDs and PCL polymers resulted in the increased tensile strength and the favorable interfacial adhesion in the ND/PCL fibrous matrices. The ND/PCL fibrous matrix with 1 wt% of ND had the highest tensile strength among the samples and also improved proliferation and differentiation of MC3T3-E1 cells. Conclusions Compared to the other samples, the ND/PCL fibrous matrix with 1 wt% of ND concentration exhibited superior performances for MC3T3 cells. The ND/PCL fibrous matrix can be potentially used for bone and dental tissue engineering.

PurposeObesity has been associated with higher total blood mercury levels, based on animal studies; however, studies that focus on children and adolescents are lacking. We aimed to assess the association between total blood mercury levels and the incidence of overweight and abdominal obesity in Korean adolescents.MethodsThe study population comprised 1,567 adolescents (793 boys and 774 girls; aged 10–19 years), who participated in the Korea National Health and Nutrition Examination Survey 2010–2013. We analyzed total blood mercury levels according to obesity status in all participants.ResultsThe geometric mean of total blood mercury levels was 1.93 µg/L. Participants with overweight (2.20 µg/L) and obesity (2.17 µg/L) had higher levels than those with normal weight (1.86 µg/L, P

The cumulative results indicate that the neutrophil to lymphocyte ratio of peripheral blood (pbNLR) is a useful prognostic factor in patients with various cancers. In contrast to peripheral blood, the bronchoalveolar lavage (BAL) fluid is in direct contact with the lung lesion. However, no study has reported on the clinical utility of the NLR of BAL fluid (bNLR) for patients with lung cancer. To investigate the clinical utility of the bNLR as a prognostic factor in patients with lung cancer, we conducted a retrospective review of the prospectively collected data. A total of 45 patients were classified into high bNLR (n = 29) and low bNLR (n = 16) groups. A high pbNLR and high bNLR were associated with a shorter overall survival (p < 0.001 and p = 0.011, respectively). A multivariable analysis confirmed that ECOG PS (p = 0.023), M stage (p = 0.035), pbNLR (p = 0.008), and bNLR (p = 0.0160) were independent predictors of overall survival. Similar to the pbNLR, a high bNLR value was associated with a poor prognosis in patients with lung cancer. Although further studies are required to apply our results clinically, this is the first study to show the clinical value of the bNLR in patients with lung cancer.

Biomolecular phase separation denotes the demixing of a specific set of intracellular components without membrane encapsulation. Recent studies have found that biomolecular phase separation is involved in a wide range of cellular processes. In particular, phase separation is involved in the formation and regulation of chromosome structures at various levels. Here, we review the current understanding of biomolecular phase separation related to chromosomes. First, we discuss the fundamental principles of phase separation and introduce several examples of nuclear/chromosomal biomolecular assemblies formed by phase separation. We also briefly explain the experimental and computational methods used to study phase separation in chromosomes. Finally, we discuss a recent phase separation model, termed bridging-induced phase separation (BIPS), which can explain the formation of local chromosome structures.

Cancer cell survival under metabolic stress is a critical step for metastasis. Here, the authors show that under glucose deprivation, Snail, a key regulator of the metastatic process, promotes survival by diverting glucose to the pentose phosphate pathway through repression of phosphofructokinase PFKP.

Structural maintenance of chromosome (SMC) proteins play a key roles in the chromosome organization by condensing two meters of DNA into cell-sized structures considered as the SMC protein extrudes DNA loop. Recent sequencing-based high-throughput chromosome conformation capture technique (Hi-C) and single-molecule experiments have provided direct evidence of DNA-loop extrusion. However, the molecular mechanism by which SMCs extrude a DNA loop is still under debate. Here, we review DNA-loop extrusion studies with single-molecule assays and introduce recent structural studies of how the ATP-hydrolysis cycle is coupled to the conformational changes of SMCs for DNA-loop extrusion. In addition, we explain the conservation of the DNA-binding sites that are vital for dynamic DNA-loop extrusion by comparing Cryo-EM structures of SMC complexes. Based on this information, we compare and discuss four compelling working models that explain how the SMC complex extrudes a DNA loop. [ABSTRACT FROM AUTHOR]

In this paper, a switching method is proposed for power device temperature-balancing in a phase-shift full-bridge (PSFB) converter. PSFB is commonly used for applications that require high efficiency, because a zero-voltage switching (ZVS) operation is possible on the primary-side. In PSFB, the circulation current complicates ZVS under a light-load condition, which generates heat. Meanwhile, the heat generated in PSFB creates a temperature deviation between the lagging leg and the leading leg, which shortens the lifetime of the power device, thereby reducing system reliability and efficiency. To solve this problem, previous studies applied a pulse-width modulation (PWM) switching method for light and medium loads, and a phase-shift switching method for the region where ZVS is possible. Although this method has the advantage of easy control, the maximum temperature of the legs of the PSFB increases with medium loads. In this paper, a temperature-balancing algorithm—a temperature-balance control—is proposed to decrease the leg temperature using switching based on position exchanges of the leading leg and lagging leg along with PWM switching. Temperature-balance control minimizes leg temperature deviation under light load conditions. The proposed control method provides a minimum temperature difference between the two legs and high efficiency.