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Hexavalent chromium (Cr(VI) contamination in water and wastewater can be treated by reduction of Cr (VI) to Cr(III) with reductants. In this study, the practicality of using FeOx crystals obtained from wastewater was evaluated by studying their reaction with Cr(VI). Cr(VI) was completely removed within 1 to 8 hours of reaction with FeOx, depending on the initial concentration up to 1.9 mM tested. After complete removal of Cr(VI) by FeOx, 22%-38% of the original concentration of Cr(VI) was converted to Cr(III) in the solution, indicating the remaining 62%-78% of the Cr(VI) was associated with the FeOx surface. Cr(VI) was removed by FeOx via reduction to Cr(III) and adsorption/precipitation on the FeOx surface. At pH 3, Cr(VI) was completely removed by FeOx within 20 minutes. Around 20% of the initially added Cr(VI) remained in the solution as Cr(III), while approximately 80% was removed from the solution. At pH 7, roughly 30% of the Cr(VI) was reduced to Cr(III) and the remaining 40% appeared to be in the solid phase after 2-hour reaction. At pH 10, approximately 40% of the Cr(VI) was removed, but Cr(III) was not observed in the solution. The Cr(VI) removal by FeOx is mainly achieved by the reduction of Cr(VI) to Cr(III) under acidic to neutral conditions, and by the adsorption of Cr(VI) onto the solid phase under alkaline conditions. The reduction of Cr(VI) occurred mainly through the reaction with ferrous iron of FeOx, which was enhanced by oxalate of FeOx, forming a soluble Fe(III)-oxalate complex with Fe(III) and reducing the passivation of the FeOx surface. Our study indicates that FeOx is effective at removing Cr(VI) at various concentrations and pH levels. [ABSTRACT FROM AUTHOR]

Microalgal biomass has been considered the third-generation biofuel production feedstock, but microalgae-derived biochar still needs to be thoroughly understood. This study aims to evaluate the production and physicochemical properties of microalgae-derived hydrochar produced by hydrothermal carbonization (HTC) process by comparison with pyrochar produced by dry thermal carbonization (DTC) process for environmental applications. Microalgal biochar was produced with commercially available Chlorella vulgaris microalgae using HTC and DTC processes under various temperature conditions. Pyrochar presented higher pH, ash contents, porosity, and surface area than hydrochar. Hydrochar gave more oxygen-containing functional groups on the surface and higher lead adsorption than pyrochar, making the microalgal hydrochar applicable in soil amendment and various environmental remediations. HTC could be an economically feasible thermochemical process for microalgal biochar production. It can produce hydrochar with high production yield from wet microalgae at low temperatures without a drying process. [ABSTRACT FROM AUTHOR]

Enzymes are widely used in industrial and pharmaceutical applications, but their activities often decrease rapidly under harsh environmental conditions such as heat, organic solvents, and dehydration. In this study, a new method for enzyme coating with polysaccharide using a rapid tyrosinase-mediated crosslinking reaction was developed. When tyrosinase reacts with a monophenol-containing biopolymer such as polysaccharide, it forms a covalent crosslink between the biopolymer and the enzyme. This crosslinking reaction create a rigid polysaccharide-coated enzyme (PCE) that protects the enzyme from harsh environmental conditions, that leads to improve the enzyme stability. To demonstrate the concept, trypsin (TR), a model enzyme with a positively charged surface, was used. Tyramine conjugated alginate polymer (AlgT), a negatively charged biocompatible polysaccharide, was used to coat TR. The AlgT was subsequently used to coat TR, forming an AlgT-TR complex. We characterized the PCE using particle size, surface charge (zeta potential), optimal pH shift, etc. Afterwards, we compared the enzyme kinetics of AlgT-TR and uncoated TR (free-TR). The AlgT-TR showed a higher activity and higher heat, storage, and water-miscible organic solvent stabilities than the free-TR. The AlgT coating method was efficient and effective to increase the thermal stability of not only TR, but also hydrolases with neutral to negative surface charges, such as elastase, subtilisin, and chymotrypsin. These results suggest that the tyrosinase-mediated crosslinking reaction is a very promising and general coating method for improving the stability of enzymes with positive surface charge, but the opposite case would be also possible. [ABSTRACT FROM AUTHOR]

The definitive treatment for end-stage renal disease is kidney transplantation, which remains limited by organ availability and post-transplant complications. Alternatively, an implantable bioartificial kidney could address both problems while enhancing the quality and length of patient life. An implantable bioartificial kidney requires a bioreactor containing renal cells to replicate key native cell functions, such as water and solute reabsorption, and metabolic and endocrinologic functions. Here, we report a proof-of-concept implantable bioreactor containing silicon nanopore membranes to offer a level of immunoprotection to human renal epithelial cells. After implantation into pigs without systemic anticoagulation or immunosuppression therapy for 7 days, we show that cells maintain >90% viability and functionality, with normal or elevated transporter gene expression and vitamin D activation. Despite implantation into a xenograft model, we find that cells exhibit minimal damage, and recipient cytokine levels are not suggestive of hyperacute rejection. These initial data confirm the potential feasibility of an implantable bioreactor for renal cell therapy utilizing silicon nanopore membranes. An implantable bioartificial kidney with a cell-containing bioreactor could be used to treat end-stage renal disease. Here the authors demonstrate the feasibility of an implantable bioreactor by maintaining human cell viability and functionality after implantation in a xenograft model. [ABSTRACT FROM AUTHOR]

Objectives: S100A8 is highly expressed in several inflammatory and oncological conditions. To address the current lack of a reliable and sensitive detection method for S100A8, we generated a monoclonal antibody with a high binding affinity to human S100A8 to enable early disease diagnosis. Results: A soluble recombinant S100A8 protein with a high yield and purity was produced using Escherichia coli. Next, mice were immunized with recombinant S100A8 to obtain anti-human S100A8 monoclonal antibodies using hybridoma technology. Lastly, the high binding activity of the antibody was confirmed and its sequence was identified. Conclusions: This method, including the production of antigens and antibodies, will be useful for the generation of hybridoma cell lines that produce anti-S100A8 monoclonal antibodies. Moreover, the sequence information of the antibody can be used to develop a recombinant antibody for use in various research and clinical applications. [ABSTRACT FROM AUTHOR]

The first-fit coloring is a heuristic that assigns to each vertex, arriving in a specified order σ , the smallest available color. The problem Grundy Coloring asks how many colors are needed for the most adversarial vertex ordering σ , i.e., the maximum number of colors that the first-fit coloring requires over all possible vertex orderings. Since its inception by Grundy in 1939, Grundy Coloring has been examined for its structural and algorithmic aspects. A brute-force f (k) n 2 k - 1 -time algorithm for Grundy Coloring on general graphs is not difficult to obtain, where k is the number of colors required by the most adversarial vertex ordering. It was asked several times whether the dependency on k in the exponent of n can be avoided or reduced, and its answer seemed elusive until now. We prove that Grundy Coloring is W[1]-hard and the brute-force algorithm is essentially optimal under the Exponential Time Hypothesis, thus settling this question by the negative. The key ingredient in our W[1]-hardness proof is to use so-called half-graphs as a building block to transmit a color from one vertex to another. Leveraging the half-graphs, we also prove that b -Chromatic Core is W[1]-hard, whose parameterized complexity was posed as an open question by Panolan et al. [JCSS '17]. A natural follow-up question is, how the parameterized complexity changes in the absence of (large) half-graphs. We establish fixed-parameter tractability on K t , t -free graphs for b -Chromatic Core and Partial Grundy Coloring, making a step toward answering this question. The key combinatorial lemma underlying the tractability result might be of independent interest. [ABSTRACT FROM AUTHOR]

We study the existence of polynomial kernels, for parameterized problems without a polynomial kernel on general graphs, when restricted to graphs of bounded twin-width. Our main result is that a polynomial kernel for k-Dominating Set on graphs of twin-width at most 4 would contradict a standard complexity-theoretic assumption. The reduction is quite involved, especially to get the twin-width upper bound down to 4, and can be tweaked to work for Connectedk-Dominating Set and Totalk-Dominating Set (albeit with a worse upper bound on the twin-width). The k-Independent Set problem admits the same lower bound by a much simpler argument, previously observed [ICALP '21], which extends to k-Independent Dominating Set, k-Path, k-Induced Path, k-Induced Matching, etc. On the positive side, we obtain a simple quadratic vertex kernel for Connectedk-Vertex Cover and Capacitatedk-Vertex Cover on graphs of bounded twin-width. Interestingly the kernel applies to graphs of Vapnik–Chervonenkis density 1, and does not require a witness sequence. We also present a more intricate O (k 1.5) vertex kernel for Connectedk-Vertex Cover. Finally we show that deciding if a graph has twin-width at most 1 can be done in polynomial time, and observe that most optimization/decision graph problems can be solved in polynomial time on graphs of twin-width at most 1. [ABSTRACT FROM AUTHOR]

For a family of graphs F , Weighted F -Deletion is the problem for which the input is a vertex weighted graph G = (V , E) and the goal is to delete S ⊆ V with minimum weight such that G \ S ∈ F . Designing a constant-factor approximation algorithm for large subclasses of perfect graphs has been an interesting research direction. Block graphs, 3-leaf power graphs, and interval graphs are known to admit constant-factor approximation algorithms, but the question is open for chordal graphs and distance-hereditary graphs. In this paper, we add one more class to this list by presenting a constant-factor approximation algorithm when F is the intersection of chordal graphs and distance-hereditary graphs. They are known as ptolemaic graphs and form a superset of both block graphs and 3-leaf power graphs above. Our proof presents new properties and algorithmic results on inter-clique digraphs as well as an approximation algorithm for a variant of Feedback Vertex Set that exploits this relationship (named Feedback Vertex Set with Precedence Constraints), each of which may be of independent interest. [ABSTRACT FROM AUTHOR]

Naegleriafowleri can cause acute primary amoebic encephalitis. It is known that contact-dependent pathogenicity in free-living amoeba may be mediated through a carbohydrate-dependent pathway. In this study, the effect of mannose on the interaction between N. fowleri and pathogenic Escherichia coli O157:H7 and non-pathogenic E. coli DH5α was analyzed. In particular, the changes in proteases expressed by N. fowleri in response to mannose were analyzed. Unlike the conventional method, mannose was treated with N. fowleri for 1 h. The association between N. fowleri and E. coli O157:H7 treated with 50-mM and 100-mM mannose was significantly reduced by approximately 70.9% and 128.5%, respectively. E. coli O157:H7 invasion was reduced by about 10.8% by 100-mM mannose. Moreover, as a result of culturing N. fowleri invaded by E. coli O157:H7 for 24 h, E. coli O157:H7 also grew about 1.2 times in the group not treated with mannose. E. coli DH5α association was reduced by 25.7% by 100-mM mannose. On the other hand, there was almost no inhibitory effect by 100-mM glucose. In the analysis in which mannose bound to either N. fowleri or bacteria and affected the interaction, there was little effect on the interaction between N. fowleri and bacteria. In zymographic analysis, about 135-kDa and 75-kDa bands were observed by 50-mM and 100-mM mannose, and two bands were significantly increased by 100-mM mannose. This study suggests that mannose can be mediated in the contact-dependent pathway of N. fowleri and will serve as a basis for inducing changes in the protease of N. fowleri by other monosaccharides. [ABSTRACT FROM AUTHOR]

Different stem cell–based strategies, especially induced pluripotent stem cells (iPSCs), have been exploited to regenerate teeth or restore biological and physiological functions after tooth loss. Further research is needed to establish an optimized protocol to effectively differentiate human iPSCs (hiPSCs) into dental epithelial cells (DECs). In this study, various factors were precisely modulated to facilitate differentiation of hiPSCs into DECs, which are essential for the regeneration of functional teeth. Embryoid bodies (EBs) were formed from hiPSCs as embryo-like aggregates, retinoic acid (RA) was used as an early ectodermal inducer, and bone morphogenic protein 4 (BMP4) activity was manipulated. The characteristics of DECs were enhanced and preserved after culture in keratinocyte serum-free medium (K-SFM). The yielded cell population exhibited noticeable DEC characteristics, consistent with the expression of epithelial cell and ameloblast markers. DECs demonstrated odontogenic abilities by exerting an inductive effect on human dental pulp stem cells (hDPSCs) and forming a tooth-like structure with the mouse tooth mesenchyme. Overall, our differentiation protocol provides a practical approach for applying hiPSCs for tooth regeneration. [ABSTRACT FROM AUTHOR]

A graph is distance-hereditary if for any pair of vertices, their distance in every connected induced subgraph containing both vertices is the same as their distance in the original graph. The Distance-Hereditary Vertex Deletion problem asks, given a graph G on n vertices and an integer k, whether there is a set S of at most k vertices in G such that G - S is distance-hereditary. This problem is important due to its connection to the graph parameter rank-width because distance-hereditary graphs are exactly the graphs of rank-width at most 1. Eiben, Ganian, and Kwon (JCSS' 18) proved that Distance-Hereditary Vertex Deletion can be solved in time 2 O (k) n O (1) , and asked whether it admits a polynomial kernelization. We show that this problem admits a polynomial kernel, answering this question positively. For this, we use a similar idea for obtaining an approximate solution for Chordal Vertex Deletion due to Jansen and Pilipczuk (SIDMA' 18) to obtain an approximate solution with O (k 3 log n + k 2 log 2 n) vertices when the problem is a Yes-instance, and we exploit the structure of split decompositions of distance-hereditary graphs to reduce the total size. [ABSTRACT FROM AUTHOR]

Excess glucocorticoids (GCs) with either endogenous or exogenous origins deteriorate skin barrier function. GCs bind to mineralocorticoid and GC receptors (MRs and GRs) in normal human epidermal keratinocytes (NHEKs). Inappropriate MR activation by GCs mediates various GC-induced cutaneous adverse events. We examined whether MR antagonists can ameliorate GC-mediated skin barrier dysfunction in NHEKs, reconstructed human epidermis (RHE), and subjects under psychological stress (PS). In a preliminary clinical investigation, topical MR antagonists improved skin barrier function in topical GC-treated subjects. In NHEKs, cortisol induced nuclear translocation of GR and MR, and GR and MR antagonists inhibited cortisol-induced reductions of keratinocyte differentiation. We identified 7,3',4'-trihydroxyisoflavone (7,3',4'-THIF) as a novel compound that inhibits MR transcriptional activity by screening 30 cosmetic compounds. 7,3',4'-THIF ameliorated the cortisol effect which decreases keratinocyte differentiation in NHEKs and RHE. In a clinical study on PS subjects, 7,3',4'-THIF (0.1%)-containing cream improved skin barrier function, including skin surface pH, barrier recovery rate, and stratum corneum lipids. In conclusion, skin barrier dysfunction owing to excess GC is mediated by MR and GR; thus, it could be prevented by treatment with MR antagonists. Therefore, topical MR antagonists are a promising therapeutic option for skin barrier dysfunction after topical GC treatment or PS. [ABSTRACT FROM AUTHOR]

Key message: CRISPR/Cas9-based multiplexed editing of SlHyPRP1 resulted in precise deletions of its functional motif(s), thereby resulting in salt stress-tolerant events in cultivated tomato. Crop genetic improvement to address environmental stresses for sustainable food production has been in high demand, especially given the current situation of global climate changes and reduction of the global food production rate/population rate. Recently, the emerging clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein (Cas)-based targeted mutagenesis has provided a revolutionary approach to crop improvement. The major application of CRISPR/Cas in plant genome editing has been the generation of indel mutations via error-prone nonhomologous end joining (NHEJ) repair of DNA DSBs. In this study, we examined the power of the CRISPR/Cas9-based novel approach in the precise manipulation of protein domains of tomato hybrid proline-rich protein 1 (HyPRP1), which is a negative regulator of salt stress responses. We revealed that the precise elimination of SlHyPRP1 negative-response domain(s) led to high salinity tolerance at the germination and vegetative stages in our experimental conditions. CRISPR/Cas9-based domain editing may be an efficient tool to engineer multidomain proteins of important food crops to cope with global climate changes for sustainable agriculture and future food security. [ABSTRACT FROM AUTHOR]

We consider the complexity of the Independent Set Reconfiguration problem under the Token Sliding rule. In this problem we are given two independent sets of a graph and are asked if we can transform one to the other by repeatedly exchanging a vertex that is currently in the set with one of its neighbors, while maintaining the set independent. Our main result is to show that this problem is PSPACE-complete on split graphs (and hence also on chordal graphs), thus resolving an open problem in this area. We then go on to consider the c-Colorable Reconfiguration problem under the same rule, where the constraint is now to maintain the set c-colorable at all times. As one may expect, a simple modification of our reduction shows that this more general problem is PSPACE-complete for all fixed c ≥ 1 on chordal graphs. Somewhat surprisingly, we show that the same cannot be said for split graphs: we give a polynomial time (nO(c)) algorithm for all fixed values of c, except c = 1, for which the problem is PSPACE-complete. We complement our algorithm with a lower bound showing that c-Colorable Reconfiguration is W[2]-hard on split graphs parameterized by c and the length of the solution, as well as a tight ETH-based lower bound for both parameters. Finally, we study c-Colorable Reconfiguration under a relaxed rule called Token Jumping, where exchanged vertices are not required to be adjacent. We show that the problem on chordal graphs is PSPACE-complete even if c is some fixed constant. We then show that the problem is polynomial-time solvable for strongly chordal graphs even if c is a part of the input. [ABSTRACT FROM AUTHOR]

Postoperative delirium is a common neuropsychiatric syndrome resulting a high postsurgical mortality rate and decline in postdischarge function. Extensive research has been performed on both human and animal delirium-like models due to their clinical significance, focusing on systematic inflammation and consequent neuroinflammation playing a key role in the pathogenesis of postoperative cognitive dysfunctions. Since animal models are widely utilized for pathophysiological study of neuropsychiatric disorders, this study aimed at examining the validity of the scopolamine-induced delirium-like mice model with respect to the neuroinflammatory hypothesis of delirium. Male C57BL/6 mice were treated with intraperitoneal scopolamine (2 mg/kg). Neurobehavioral tests were performed to evaluate the changes in cognitive functions, including learning and memory, and the level of anxiety after surgery or scopolamine treatment. The levels of pro-inflammatory cytokines (IL-1β, IL-18, and TNF-α) and inflammasome components (NLRP3, ASC, and caspase-1) in different brain regions were measured. Gene expression profiles were also examined using whole-genome RNA sequencing analyses to compare gene expression patterns of different mice models. Scopolamine treatment showed significant increase in the level of anxiety and impairments in memory and cognitive function associated with increased level of pro-inflammatory cytokines and NLRP3 inflammasome components. Genetic analysis confirmed the different expression patterns of genes involved in immune response and inflammation and those related with the development of the nervous system in both surgery and scopolamine-induced mice models. The scopolamine-induced delirium-like mice model successfully showed that analogous neuropsychiatric changes coincides with the neuroinflammatory hypothesis for pathogenesis of delirium. [ABSTRACT FROM AUTHOR]

Streptomyces spp. have been isolated from different environmental niches and are known to exhibit diversity in secondary metabolism. They have complex regulation system to control secondary metabolism, however it is difficult to prioritize the importance of specific regulator among the thousands of global or cluster-situated genes that may regulate secondary metabolism in different Streptomyces strains. Here we suggest a simple homology-based selection method to find out important regulators by comparing seven Streptomyces strains finding highly homologous regulators in various Streptomyces strains and showed highly homologous 11 regulators containing four well known regulators such as BldM, IclR, WhiD and NdgR. Among various regulators, we showed a putative transcriptional regulator in Streptomyces coelicolor A3(2), SCO1463 playing a pivotal role in growth, antibiotic production (actinorhodin[ACT] and undecylprodigiosin [RED] production), and production/utilization of organic acids such as propionate and succinate by making comparisons between the deletion mutant and the wild type strain. Although high homology in various strains does not always mean the importance of a gene, we suggested a criterion on which regulator should be studied first and which would be more important among more than one thousand regulators. [ABSTRACT FROM AUTHOR]

Purpose: There is a distinct lack of studies on the impact of urinary incontinence on quality of life in middle-aged and older Korean women, despite numerous clinical observations supporting its negative influence. The association between urinary incontinence and quality of life and subjective health state was investigated with various covariates to identify mediating variables.Methods: A nationally representative sample of Korean women aged ≥ 45 years (n = 4020) with data for urinary incontinence, quality of life, health-related items and covariates from the 4th Korean Longitudinal Study of Ageing (KLoSA, 2012) were analyzed in a cross-sectional study. Association between urinary incontinence and quality of life and subjective health state adjusted for using sociodemographic factors and health behavior, and regression analysis in adjusted complex sampling design to determine regression coefficients with 95% confidence intervals.Results: Prevalence of urinary incontinence in middle-aged and older Korean women was 27.5% (n = 1107). The negative relationship between urinary incontinence and quality of life was maintained in full adjustments (sociodemographic factors, health behavior, somatic health, and mental health) with mental health exerting greatest influence on the association between urinary incontinence and quality of life. Moreover, in presence of urinary incontinence symptoms, aggravation of urinary incontinence symptoms held a more negative relationship with quality of life compared to similarly maintained state.Conclusions: Urinary incontinence has a negative association with quality of life and subjective health state, and psychological factors which are implicated in old age may be of importance in urinary incontinence patient management. [ABSTRACT FROM AUTHOR]

A potent phytoestrogen, (S)-equol, is a promising isoflavone derivative drawing our great attention owing to its various biological and clinical benefits. Through selective activation of the estrogen receptor ERβ or androgen receptor, (S)-equol reduces menopausal symptoms, osteoporosis, skin aging, hair loss, and incidence of prostate or ovarian cancers without adverse effects. Traditional biosynthesis of (S)-equol exploited non-productive natural equol-producing anaerobic bacteria that mainly belong to Coriobacteriaceae isolated from human intestine. Recently, we developed a recombinant Escherichia coli strain which could convert daidzein into (S)-equol effectively under an aerobic condition. However, the yield was limited up to about the 200 mg/L level due to unknown reasons. In this study, we identified that the bottleneck of the limited production was the low solubility of isoflavone (i.e., 2.4 mg/L) in the reaction medium. In order to solve the solubility problem without harmful effect to the whole-cell catalyst, we applied commercial hydrophilic polymers (HPs) and a polar aprotic co-solvent in the reaction medium. Among the examined water-soluble polymers, polyvinylpyrrolidone (PVP)-40k was verified as the most promising supplement which increased daidzein solubility by 40 times and (S)-equol yield up to 1.22 g/L, the highest ever reported and the first g/L level biotransformation. Furthermore, PVP-40k was verified to significantly increase the solubilities of other water-insoluble natural polyphenols in aqueous solution. We suggest that addition of both HP and polar aprotic solvent in the reaction mixture is a powerful alternative to enhance production of polyphenolic chemicals rather than screening appropriate organic solvents for whole-cell catalysis of polyphenols. [ABSTRACT FROM AUTHOR]

Ovarian follicle in vitro culture is a promising fertility preservation option to avoid risk of reintroduction of malignant cells. The objective of this study is to compare 4 different follicle isolation methods from ovarian tissue and evaluate the effect of follicle isolation on further in vitro follicle culture and oocyte competency. Mouse ovaries were dissected and randomly divided into 4 groups according to follicle isolation method: mechanical (MCH) isolation, mincing (MNC) isolation, enzymatically digestion using collagenase (COL), and enzymatically digestion using liberase (LIB). The isolated early secondary follicles were cultured for day 10, and ovulation induction was conducted. Follicular diameter and concentrations of steroid hormone in spent media were measured. Also, follicular survival rate and pseudo-antrum formation rate were examined. After ovulation induction, the cumulus oocyte complexes rate and the number of mature oocyte, normal spindle rate, and mitochondrial activity in ovulated oocyte were counted. After in vitro culture, follicular diameter was significantly greater in MNC and MCH group than other groups. Also, follicle survival rate was significantly higher in MNC and MCH groups than other groups. The MNC group had made a result that significantly improved the mature oocyte rate than other groups. The normal meiotic spindle and chromosome rate is significantly higher in MNC and MCH groups than other groups. The MNC method showed significantly improved rate of follicle diameter, survival, pseudo-antrum formation, a mature oocyte, and normal spindle in ovulated oocyte after in vitro culture. Based on the results, MNC method can be an alternative for MCH method that is laborious and time-consuming. [ABSTRACT FROM AUTHOR]

Enamel knot (EK) is known to be a central organ in tooth development, especially for cusp patterning. To trace the exact position and movement among the inner dental epithelium (IDE) and EK cells, and to monitor the relationship between the EK and cusp patterning, it is essential that we understand the cell cycle status of the EK in early stages of tooth development. In this study, thymidine analogous (IdU, BrdU) staining was used to evaluate the cell cycle phase of the primary EK at the early casp stage (E13.0) and the gerbil embryo (E19) in a developing mouse embryo. The centerpiece of this study was to describe the cell cycle phasing and sequencing during proliferation in the IDE according to the expression of IdU and BrdU following their injection at calculated time points. The interval time between IdU injection and BrdU injection was set at 4 h. As a result, the cell cycle in the IDE of the mouse and gerbil was found to be synchronous. Conversely, the cell cycle in primary EKs of mice was much longer than that of the IDE. Therefore, the difference of cell cycle of the IDE and the EK is related to the diversity of cusp patterning and would provide a new insight into tooth morphogenesis. [ABSTRACT FROM AUTHOR]

Most secondary metabolism in Actinobacteria is controlled by multi-layered, gene-regulatory networks. These regulatory mechanisms are not easily identified due to their complexity. As a result, when a strong transcriptional regulator (TR) governs activation of biosynthetic pathways of target antibiotics such as actinorhodin (ACT), additional enhancement of the biosynthesis is difficult in combination with other TRs. To find out any “synergistic transcriptional regulators (sTRs)” that show an additive effect on the major, often strong, transcriptional regulator (mTR), here, we performed a clustering analysis using the transcriptome datasets of an mTR deletion mutant and wild-type strain. In the case of ACT biosynthesis in Streptomyces coelicolor, PhoU (SCO4228) and RsfA (SCO4677) were selected through the clustering analysis, using AfsS (SCO4425) as a model mTR, and experimentally validated their roles as sTRs. Furthermore, through analysis of synergistic effects, we were able to suggest a novel regulation mechanism and formulate a strategy to maximize the synergistic effect. In the case of the double TR mutant strain (ΔrsfA pIBR25::afsS), it was confirmed that the increase of cell mass was the major cause of the synergistic effect. Therefore, the strategy to increase the cell mass of double mutant was further attempted by optimizing the expression of efflux pump, which resulted in 2-fold increase in the cell mass and 24-fold increase in the production of ACT. This result is the highest ACT yield from S. coelicolor ever reported. [ABSTRACT FROM AUTHOR]

Background: Laparoscopic surgery involves the creation of a carbon dioxide (CO2) pneumoperitoneum to facilitate a clear surgical view, which may result in an elevated intracranial pressure (ICP). Depending on the surgical area, steep Trendelenburg positioning may be used as well, further increasing the ICP. The objective of this study was to assess the effects of laparoscopic surgery on changes in ICP assessed by ultrasonographic measurement of optic nerve sheath diameter (ONSD), which is a generally accepted simple, reliable, and non-invasive ICP measurement technique.Methods: A computerized literature search was performed in August 2016 to identity prospective studies that measured ONSD to assess ICP changes during laparoscopic surgery. The primary outcome was the change in ONSD during the early (0-30 min) and late (30-120 min) periods after initiating pneumoperitoneum, compared with baseline values measured after anesthesia induction. Mean differences (MDs) with 95% confidence intervals [CIs] were calculated.Results: Nine observational studies and one randomized controlled trial, with a total of 460 subjects, were analyzed. Compared to the baseline value after anesthesia induction, significant increases in ONSD were observed in both the early period (MD 0.46, 95% CI 0.31-0.61, P < 0.001, I 2 = 97.3%) and late period (MD 0.67, 95% CI 0.20-1.14, P = 0.005, I 2 = 99.2%). Comparing the ONSD during the early and late periods revealed no significant differences over time.Conclusions: The current meta-analysis revealed that ICP elevation during laparoscopy could be anticipated through a significant increase in the ONSD in the early (0-30 min) and late (30-120 min) periods during CO2 pneumoperitoneum. [ABSTRACT FROM AUTHOR]

There is limited information on the role of GABA type A receptors (GABARs) containing α1, α5 and γ2 subunits in learning and memory. Here, we assessed the possible role of such receptors in spatial learning using the multiple T-maze (MTM) paradigm. C57BL/6J mice were trained in the MTM which induced elevated levels of α1 and α5 subunit-containing hippocampal GABAR complexes. Moreover, spatial learning evoked a significant increase in the colocalization of α1 and α5 subunits in both, CA1 and dentate gyrus regions of the hippocampus suggesting the formation of complexes containing both subunits. Additionally, the presence of α1, α5 and γ2 subunits in high molecular weight GABARs was detected and significant correlation in the level of α1-containing complexes with those containing α5 and γ2 subunits was demonstrated. Accordingly, α1 deficiency led to decreased levels of γ2 subunit-containing complexes, however, had no effect on α5-containing ones. On the other hand, α1 knockout mice showed impaired performance in the MTM correlating with increased levels of α5 subunit-containing GABARs in comparison to trained floxed control animals which quickly learned the task. Taken together, these results suggest that α1, α5 and γ2-containing hippocampal GABAR complexes play an essential role in spatial learning and memory in which targeted disruption of the α1 subunit produces profound deficits. [ABSTRACT FROM AUTHOR]

Menopausal women are associated with an increase in obesity accompanying changes in the body's condition and composition. Polygonatum stenophyllum (PS) rhizome, which is a traditional herbal remedy, has been used to treat various diseases including obesity. However, the effect of PS on menopausal obesity remains unclear. Female C57BL/6 mice were ovariectomized (OVX) and fed on high fat diet (HFD) to induce menopausal obesity. Aqueous extract of PS of 1, 10, and 100 mg/kg was orally administrated for 6 weeks after 7 weeks of induction. The weights of body, uterine, and ovarian fat were investigated. Histological analysis was performed to monitor the changes of liver and fat. In addition, lipid profiles were measured in serum and the expression of lipolysis-related enzymes was analyzed in uterine tissues. PS significantly decreased the weights of body and ovarian fat and increased the uterine weight compared to control group. Administration of PS significantly decreased the adipocyte diameter and the lipid droplets within the hepatocytes. In addition, PS-treated mice had lower levels of triglyceride (TG), total cholesterol, and LDL-cholesterol than control mice. The expression of lipolysis-related genes, including adipose triglyceride lipase (ATGL) and hormone-sensitive lipase (HSL), was increased in PS-treated groups. Taken together, these results demonstrate that PS might have efficacy on menopausal obesity by activating ATGL and HSL. [ABSTRACT FROM AUTHOR]

The transcription factor Sox2 is a stem cell marker that dictates cell lineage. It has been shown to mark the epithelial stem cells of the continuously growing mouse incisors. Sox2 also interferes with Wnt signaling by binding to β-catenin, a central mediator of the Wnt pathway. We show that these functions of Sox2 are essential for mouse molar development. Sox2 has previously been shown to play a role in the formation of new teeth from the existing dental epithelium. To assess Sox2 function related to cell migration within a tooth, we monitored cell movement by using a DiI system and observed that DiI moves from molar 1 to molar 2 during tooth development. However, upon temporal knockdown of Sox2, DiI remains in the molar 1 region. This study also provides novel insights into the role of Sox2 and the important validation of Sox2 as a potent target in Wnt signaling during tooth development. Our data reveal that the degradation of Wnt signaling caused by the knockdown of Sox2 results in a lack of cell migration during tooth development. [ABSTRACT FROM AUTHOR]

Manufacturing can be defined as the transformation of raw materials into desired products by various processes, such as machining, welding and coating. Today, laser and arc heat sources are largely used as the means for processing raw materials. The laser is one of the most widely used non-contact thermal energy sources in various processes, and the development of laser processes and devices for effective manufacturing is still ongoing. Arc heat sources are widely used in welding and coating processes. In particular, the types of welding processes using arc heat sources are very different depending on the materials used and the purpose of welding. In this paper, individual processes using laser and arc heat that have been reported over the past five years are reviewed, including machining, welding, sintering and coating. Then, hybrid processes that use laser and arc heat sources together are also reviewed. The final part of this review provides a summary and discusses future trends for individual and hybrid processes using laser and arc heat sources. [ABSTRACT FROM AUTHOR]

High-grade gliomas are considered the most malignant of brain tumors and have a poor prognosis. In a previous study, we showed that LIM domain only 2 (LMO2) regulates glioma stem cell properties and tumor angiogenesis and gave rise to highly invasive glioma xenografts. Glioma invasion in the surrounding parenchymal tissues is a major hurdle with respect to eliminating glioma by surgery. Invasive glioma cells are considered one of the main culprits for the recurrence of tumors after therapies. In the current study, we focused on determining the molecular mechanism(s) by which LMO2 regulates glioma cell migration and invasion. Forced expression of LMO2 in human U87MG glioma cells led to glioma invasion, as determined by in vivo xenograft assays and enhanced in vitro migration and invasion. LMO2 was associated with increased levels of cytosolic p27 protein. LMO2 possibly induced the stabilization and augmented interactions between p27 and RhoA. We knocked down the expression of p27, which led to a decrease in LMO2-driven glioma cell migration and invasion. Taken together, our findings indicate that LMO2 promotes glioma cell migration and invasion by increasing the levels of cytosolic p27. [ABSTRACT FROM AUTHOR]

In recent years, there has been an increase in the adoption of Shari'a in Europe and North America as an arbitration protocol for the resolution of potential contractual disputes. In a largely secular Western business environment, this reality raises corporate policy implications for business organizations. In particular, questions are raised about whether Shari'a is by nature too unpredictable-and too dismissive of women's rights-to be properly and ethically permitted by Western companies as a possible dispute resolution alternative. This article examines the dynamics and factors that are involved as corporate managers decide whether Shari'a arbitration ought to be banned entirely from contractual negotiations. Arguments for and against the inclusion of a Shari'a arbitration clauses in commercial contracts and contract negotiations are presented. The article concludes that while managers should exercise great prudence and consider the moral implications of negotiating arbitration clauses, an organizational ban of the use of faith-informed arbitration generally, or Shari'a in particular, would be neither morally required nor optimally serve the interests of the organization or its stakeholders. [ABSTRACT FROM AUTHOR]

Peremptory norms of general international law ( jus cogens) are universally binding prohibitions that override any consideration for non-compliance (e.g., genocide and slavery). The question is how nonconsensual norms emerge from a consensual international legal order. It appears that either the peremptoriness of jus cogens renders consent superfluous to the norm's binding force or consent divests jus cogens of its peremptory status. The goal of this paper is to resolve the dilemma by explaining why jus cogens is exempt from the general requirement of consent that binds states to the rules of international law. The paper provides an impartiality-based account of enforcement that explains why a state's refusal to give consent to jus cogens may be overridden in a consensual legal order. [ABSTRACT FROM AUTHOR]

The activation of Wingless-type (Wnt)/β-catenin signaling is of fundamental importance in organogenesis. Wnt signaling is also known to regulate signaling crucial for tooth development. However, the underlying mechanism of Wnt activation or inhibition remains largely unknown. Here, we demonstrate that Wnt inhibitory factor 1 (Wif1), a secreted Wnt antagonist, localizes to the dental epithelium and mesenchyme during early tooth development. Specifically, Wif1 is strictly expressed in the enamel knot at embryonic day 14.5 (E14.5) and E16.5. The functional significance of Wif1 during tooth morphogenesis remains to be clarified. Our results reveal that the promotion of apoptosis by the knockdown of Wif1 leads to a delay in an early event during tooth development. This study therefore provides novel insights into the role of Wif1 and validates Wif1 as a potent target in WNT signaling during tooth development. We suggest that the enamel knots are central regulators of tooth development. Furthermore, Wif1 localizes to the enamel knot in which Wif1 regulates apoptosis by mediating and regulating Wnt-β-catenin signaling. Thus, Wif1 plays an essential role in tooth development. [ABSTRACT FROM AUTHOR]

Gastrin-releasing peptide (GRP) is considered to be one of the cancer growth factors. This peptide's receptor (GRPR) is known as a G protein-coupled receptor, regulating intracellular calcium storage and releasing signals. This study is the first to investigate the function of GRP during mouse incisor development. We hypothesized that GRP is one of the factors that affects the regulation of calcification during tooth development. To verify the expression pattern of GRP, in situ hybridization was processed during incisor development. GRP was expressed at the late bell stage and hard tissue formation stage in the epithelial tissue. To identify the genuine function of GRP during incisor development, a gain-of-function analysis was performed. After GRP overexpression in culture, the phenotype of ameloblasts, odontoblasts and predentin was altered compared to control group. Moreover, enamel and dentin thickness was increased after renal capsule transplantation of GRP-overexpressed incisors. With these results, we suggest that GRP plays a significant role in the formation of enamel and dentin by regulating ameloblasts and predentin formation, respectively. Thus, GRP signaling is strongly related to calcium acquisition and secretion during mouse incisor development. [ABSTRACT FROM AUTHOR]

Hydroxylated fatty acids (HFAs) are used as important precursors for bulk and fine chemicals in the chemical industry. Here, to overproduce long-chain (C16-C18) fatty acids and hydroxy fatty acid, their biosynthetic pathways including thioesterase ( Lreu_0335) from Lactobacillus reuteri DSM20016, β-hydroxyacyl-ACP dehydratase ( fabZ) from Escherichia coli, and a P450 system (i.e., CYP153A from Marinobacter aquaeolei VT8 and camA/ camB from Pseudomonas putida ATCC17453) were overexpressed. Acyl-CoA synthase ( fadD) involved in fatty acid degradation by β-oxidation was also deleted in E. coli BW25113 . The engineered E. coli FFA4 strain without the P450 system could produce 503.0 mg/l of palmitic (C) and 508.4 mg/l of stearic (C) acids, of which the amounts are ca. 1.6- and 2.3-fold higher than those of the wild type. On the other hand, the E. coli HFA4 strain including the P450 system for ω-hydroxylation could produce 211.7 mg/l of ω-hydroxy palmitic acid, which was 42.1 ± 0.1 % of the generated palmitic acid, indicating that the hydroxylation reaction was the rate-determining step for the HFA production. For the maximum production of ω-hydroxy palmitic acid, NADH, i.e., an essential cofactor for P450 reaction, was overproduced by the integration of NAD-dependent formate dehydrogenase (FDH) from Candida boidinii into E. coli chromosome and the deletion of alcohol dehydrogenase (ADH). Finally, the NADH-level-optimized E. coli strain produced 610 mg/l of ω-hydroxy palmitic acid (ω-HPA), which was almost a threefold increase in its yield compared to the same strain without NADH overproduction. [ABSTRACT FROM AUTHOR]

Copper (Cu) is often found strongly bound to natural organic matter (NOM) in soil through the formation of strong Cu-NOM complexes. Therefore, in order to successfully remediate Cu-contaminated soils, effective removal of Cu bound to soil organic matter should be considered. In this study, we investigated soil washing methods for Cu removal from a synthetic Cu-contaminated model silica soil coated with humic acid (HA) and from field contaminated soil. Various reagents were studied to extract Cu bound to NOM, which included oxidant (HO), base (NaOH), and chelating agents (citric acid and ethylenediaminetetraacetic acid (EDTA)). Among the wash reagents, EDTA extracted Cu most effectively since EDTA formed very strong complexes with Cu, and Cu-HA complexes were transformed into Cu-EDTA complexes. NaOH extracted slightly less Cu compared to EDTA. HA was effectively extracted from the model soil under strongly alkaline conditions with NaOH, which seemed to concurrently release Cu bound to HA. However, chemical oxidation with HO was not effective at destroying Cu-HA complexes. Fourier transform infrared spectroscopy and elemental analysis revealed that chelating agents such as citrate and EDTA were adsorbed onto the model soil via possible complexation between HA and extraction agents. The extraction of Cu from a field contaminated soil sample was effective with chelating agents, while oxidative removal with HO and extractive removal with NaOH separated negligible amounts of Cu from the soil. Based on these results, Cu bound to organic matter in soil could be effectively removed by chelating agents, although remnant agents may remain in the soil. [ABSTRACT FROM AUTHOR]

Glioblastoma is a highly aggressive primary brain tumor in which the majority of cancer cells are undifferentiated. One of the most common oncogenic drivers for this malignancy is the epidermal growth factor receptor variant III (EGFRvIII), which lacks a portion of the extracellular ligand-binding domain due to deletion of exons 2-7 of the EGFR gene. EGFRvIII plays a critical role in tumor progression, promoting acquisition of stem cell-like features including an undifferentiated state and therapy resistance. However, the molecular mechanisms by which EGFRvIII contributes to cancer cell aggressiveness remain poorly understood. Here, we show that EGFR expression correlates with JAGGED1 expression in glioblastoma patients. Overexpression of EGFRvIII in glioma cell lines augmented JAGGED1 expression at the transcriptional level through the mitogen-activated protein kinase signaling pathway. Consequently, EGFRvIII overexpression drove partial dedifferentiation of glioma cells, as determined by tumorsphere-forming ability and expression of stem cell markers, through JAGGED1 induction. EGFRvIII-mediated radioresistance, but not chemoresistance, was also modulated by JAGGED1. Taken together, our results provide new insight into the mechanism underlying EGFRvIII-driven glioblastoma aggressiveness. [ABSTRACT FROM AUTHOR]