In 2017, Leoni et al. reported myticalins as novel cationic linear antimicrobial peptides obtained from marine mussels. The authors focused on myticalin A6 (29 amino acids), which has a relatively ...short chain length among myticalins and contains a repeating X-proline(Pro)-arginine (Arg) sequence in its structure. We investigated the antimicrobial activity of myticalin A6 against Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus (S. aureus). Fragment derivatives of myticalin A6 were synthesized, and the site required for expression of antimicrobial activity was examined. To investigate the structure–antimicrobial activity relationship of myticalin A6, short-chain derivatives and partially substituted derivatives were synthesized, and the antimicrobial activity was measured. Furthermore, some cyclized derivatives were synthesized and examined for antimicrobial activity. Circular dichroism (CD) spectroscopy of myticalin A6 and its derivatives was carried out to evaluate the secondary structure. Myticalin A6 exhibited an antimicrobial activity of 1.9 µM against S. aureus. Myticalin A6 (3–23)-OH (21 amino acids) exhibited an antimicrobial activity of 2.4 µM against S. aureus, suggesting that the X-Pro-Arg repeat sequence is important for antimicrobial activity. Derivatives with different CD measurement results from myticalin A6 (3–23)-OH exhibited decreased activity. The myticalin A6 (3–23)-OH derivative in which all Arg residues were replaced with lysine (Lys) residues exhibited reduced antimicrobial activity against S. aureus. We succeeded in synthesizing cyclic derivatives using 9-fluorenylmethoxycarbonyl (Fmoc)-aspartic acid (Asp)(Wang resin)-2-phenylisopropyl ester (OPis), but the yield of derivatives with 21 amino acids was decreased. The myticalin derivatives synthesized in this study did not exhibit any enhancement in antimicrobial activity due to cyclization.
Summary
The zygnematophycean algae occupy an important phylogenetic position as the closest living relatives of land plants. Reverse genetics is quite useful for dissecting the functions of genes. ...However, this strategy requires genetic transformation, and there are only a few reports of successful transformation in zygnematophycean algae.
Here, we established a simple and highly efficient transformation technique for the unicellular zygnematophycean alga Closterium peracerosum‐strigosum‐littorale complex using a square electric pulse‐generating electroporator without the need for cell wall removal.
Using this method, the transformation efficiency increased > 100‐fold compared with our previous study using particle bombardment. We also succeeded in performing CRISPR/Cas9‐based gene knockout using this new method.
Our method requires only small amounts of labor, time and incubator space. Moreover, our technique could also be utilized to transform other charophycean algae with available genome information by optimizing the electric pulse conditions.
The Polycomb-group (PcG) repressive complex-1 (PRC1) forms microscopically visible clusters in nuclei; however, the impact of this cluster formation on transcriptional regulation and the underlying ...mechanisms that regulate this process remain obscure. Here, we report that the sterile alpha motif (SAM) domain of a PRC1 core component Phc2 plays an essential role for PRC1 clustering through head-to-tail macromolecular polymerization, which is associated with stable target binding of PRC1/PRC2 and robust gene silencing activity. We propose a role for SAM domain polymerization in this repression by two distinct mechanisms: first, through capturing and/or retaining PRC1 at the PcG targets, and second, by strengthening the interactions between PRC1 and PRC2 to stabilize transcriptional repression. Our findings reveal a regulatory mechanism mediated by SAM domain polymerization for PcG-mediated repression of developmental loci that enables a robust yet reversible gene repression program during development.
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•PRC1 forms visible subnuclear clusters at its target loci in mouse primary cells•The polymerization of the Phc2 SAM domain is required for PRC1 clustering•Clustering of PRC1 links to chromatin condensation and gene silencing•PRC1 clustering associates with stable binding of PRC1/PRC2 at its target loci
Gene silencing by the Polycomb-repressive complex-1 (PRC1) is crucial for embryogenesis. Isono et al. show that subnuclear PRC1 clustering at its target genes is mediated by the polymerization capacity of the Phc2 SAM domain and associates with stable PRC1/PRC2 binding, trimethylation of histone H3 Lys27, and robust gene silencing.
Deep-squat movement is one of the most important activities for independent living. Although a large range of motion of lower extremity joints in the sagittal plane is required for deep-squat ...movement, older individuals exhibit reduced mobility of lower limb joints. However, the effect of aging on deep-squat movement remains unclear. The purpose of this study was to investigate the age-related changes in the whole-body movement and lower extremity joint kinematics and kinetics during deep-squat movement. Twelve older and nineteen younger individuals performed the deep-squat movement, with knee flexion exceeding 100 degrees, and a motion analysis system and force plates collected their motion data. The median (interquartile range) age of older and younger individuals was 76.5 (3.3) and 30.0 (9.0) years, respectively. The deep-squat depth was significantly shallower in older individuals than in younger individuals (P < 0.05). Furthermore, older individuals exhibited smaller ankle dorsiflexion and knee flexion angles, larger trunk flexion angles, and greater forward displacement of the whole-body center of mass during deep-squat movement (P < 0.05). In terms of kinetic variables, older individuals exhibited smaller contributions of knee extension moment and larger contributions of hip extension moment to the support moment in the timing of the maximum support moment during deep-squat movement (P < 0.05). Our results indicated that older individuals have greater difficulty with deeper-squat movement and smaller contribution of knee extension moment to support body weight using trunk, hip, and ankle movements during deep-squat movement.
Sit-to-stand (STS) movements from low seat height are not easily executed by older individuals. Although young individuals increase their lower limb muscle power (LLMP) based on the product of the ...ground reaction force (GRF) and center of mass velocity (CoMv) during STS movement from a low seat height, it remains unclear whether seat height has an effect on LLMP during STS movement in older individuals. The present study aimed to investigate differences in the LLMP during STS movements when seat height is lowered between young and older individuals. Twelve older and twelve height-matched young individuals were instructed to perform STS movements from low (20 cm), middle (40 cm), and high (60 cm) seat heights. STS movement and GRF were obtained by a motion analysis system and force plates. In the low-seat-height condition, the forward and upward LLMPs and the upward CoMv were significantly lower in older individuals than those in young individuals, but the forward CoMv was not. The completion time of STS movement from a low seat height was significantly longer in older individuals than in young individuals. Our findings suggest that the slower upward CoMv due to the lower upward LLMP extends the completion time of STS movement from a low seat height in older individuals. Furthermore, in the low-seat-height condition, older individuals may move their center of mass (CoM) forward in a different way when compared with young individuals, and they may not use forward LLMP for moving CoM forward.
Nuclear/chromosomal integrity is an important prerequisite for the assessment of embryo quality in artificial reproductive technology. However, lipid-rich dark cytoplasm in bovine embryos prevents ...its observation by visible light microscopy. We performed live-cell imaging using confocal laser microscopy that allowed long-term imaging of nuclear/chromosomal dynamics in bovine in vitro fertilised (IVF) embryos. We analysed the relationship between nuclear/chromosomal aberrations and in vitro embryonic development and morphological blastocyst quality. Three-dimensional live-cell imaging of 369 embryos injected with mRNA encoding histone H2B-mCherry and enhanced green fluorescent protein (EGFP)-α-tubulin was performed from single-cell to blastocyst stage for eight days; 17.9% reached the blastocyst stage. Abnormalities in the number of pronuclei (PN), chromosomal segregation, cytokinesis, and blastomere number at first cleavage were observed at frequencies of 48.0%, 30.6%, 8.1%, and 22.2%, respectively, and 13.0%, 6.2%, 3.3%, and 13.4%, respectively, for abnormal embryos developed into blastocysts. A multivariate analysis showed that abnormal chromosome segregation (ACS) and multiple PN correlated with delayed timing and abnormal blastomere number at first cleavage, respectively. In morphologically transferrable blastocysts, 30-40% of embryos underwent ACS and had abnormal PN. Live-cell imaging may be useful for analysing the association between nuclear/chromosomal dynamics and embryonic development in bovine embryos.
Bevacizumab (Bev) plays the central role of the adjuvant therapy for patients with ovarian carcinoma. The aim of our study was to examine whether differences in the administration of Bev influence ...the prognosis of patients.
Patients with ovarian carcinoma who received treatment at two hospitals between 1999 and 2020 were identified. Patients treated with weekly low-dose administration of Bev (100 mg Bev on days 1 and 8 and 200 mg Bev on day 15, monthly) at one hospital (group A) and those with monthly high-dose administration of Bev (15 mg/kg of Bev on day 1, monthly) at another hospital (group B) were retrospectively compared.
Among the total patients, 44 were assigned to group A and 33 were assigned to group B. More patients in group A had advanced disease (p = 0.03) and a lower dose of Bev at the first time during the first cycle administration (p < 0.01) than in group B. Progression-free survival (PFS) was better in group A than in group B (p < 0.01). Multivariate analysis revealed that group A was a better prognostic factor for PFS (hazard ratio 0.53, p = 0.03). Stable duration was longer in group A than in group B (p < 0.01). The incidences of adverse effects, including hematological toxicities such as neutropenia (p = 0.01) and nonhematological toxicities such as hypertension (p < 0.01), intestinal obstruction (p < 0.01), and thromboembolic events (p < 0.01), were lower in group A than in group B.
Weekly low-dose administration of Bev might improve prognosis and decrease the frequency of adverse effects associated with this drug although the prospective study was needed to get corroboration.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Many companies have created business continuity plans, which are plans for disaster preparedness and post-disaster response in order to minimize damage in the event of a disaster. We can analyze what ...risks companies are prioritizing and how much countermeasures they are taking against various types of risks. Therefore, we conducted a questionnaire on the frequency of disasters assumed by BCP and the target recovery period. Here, we will explain the contents and results of the questionnaire survey and report the analysis focusing on the differences depending on the region of work and industry.
Interacting structures between hVDR residues and ligand 2 depending on the protonation states of His305 and His397
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•We investigated specific interactions between vitamin D receptor ...(VDR) and its ligand.•Ab initio fragment molecular orbital (FMO) method was used for calculations.•Stable protonation states of His residues in VDR were precisely determined by FMO.•The difference in chirality of ligands causes the difference in His protonations.
Vitamin D is recognized to play important roles in the onset of immunological diseases as well as the regulation of the amount of Ca in the blood. Since these physiological actions caused by active vitamin D are triggered by the specific interaction between the vitamin D receptor (VDR) and active vitamin D, many types of compounds have been developed as potent ligands against VDR. It was found that the binding affinity between VDR and its ligand depends significantly on the chirality of the ligand. However, the reason for the dependence has, thus far, not been elucidated. In the present study, we investigated the specific interactions between VDR and some ligands with different chirality, using ab initio fragment molecular orbital (FMO) calculations. The FMO results reveal that two histidine residues of VDR contribute significantly to the binding between VDR and ligand and that their protonation states can affect the specific interactions between VDR and ligand. We therefore considered other possible protonation states of these histidine residues and determined their most stable states, using the ab initio FMO calculations. The results illustrate the possibility that the difference in the chirality of a ligand can induce the change in protonation states of the histidine residues of VDR existing near the ligand. This finding provides an important warning that the protonation states of histidine residues existing near the ligand should be considered more precisely in the molecular simulations for investigating the specific interactions between protein and ligand.
Here, we designed and synthesized two types of bi‐functional immobilized polymer catalysts based on the prolineamide‐acid combination for direct enantioselective aldol reaction in flow systems. ...Conventional bi‐functional catalysts in which the two functions are present on the same graft polymer afforded up to 99 % yield and >99 % enantiomeric excess (ee) in a recirculating flow system. We also investigated bi‐functional catalysts in which the two functions are located on different graft polymers. We present a straightforward catalyst immobilization method that allows two different catalysts located on different graft polymers to be introduced separately onto the same polymer by conducting two successive steps of radiation‐induced graft polymerization process (RIGP). We confirmed that the graft polymers (grafted polycatalyst and polyacrylic acid chain) interact with each other to promote the aldol reaction with high conversion and ee. This design strategy may be superior to the conventional approach for synthesizing catalysts in which multiple functions interact.
Bi‐functional immobilized polymer catalysts via a two‐step radiation‐induced graft polymerization process (RIGP) was designed and synthesized. We also investigated bi‐functional catalysts in which the two functions are located on different graft polymers. We confirmed that the graft polymers (grafted polycatalyst and polyacrylic acid chain) interact with each other to promote the aldol reaction with high conversion and ee. This design strategy may be superior to the conventional approach for synthesizing catalysts in which multiple functions interact.
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