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Four control systems are generated using Matlab software based on different regulators for the granulation process in a fluidized bed: PID controller and optimal LQR for linear systems and MPC and those based on fuzzy logic for nonlinear systems. For each control system, transient characteristics are obtained and system efficiency indicators are given. [ABSTRACT FROM AUTHOR]

The object of the conducted research is dynamically unstable objects and processes of the third order with a transfer function of the third order. The problem that has been considered and solved is related to the provision of dynamically unstable systems with such a stable tate in which transients are set to the technical optimum. Analytical formulas have been obtained to determine the values of the roots of a third-order characteristic equation tuned to a technical optimum. The only variable of the obtained mathematical expressions is the time constant of the system or object, which determines the time of establishment or termination of periodic processes. Since the obtained analytical expressions directly determine the constant coefficients of the polynomial of the characteristic equation based on just one variable, which in the physical sense is a normalized value of the transition time, the synthesis of any dynamically unstable system leads to a state in which the system is optimized, according to the condition of technical optimum. In other words, only the analytical expressions obtained for the coefficients of the characteristic equation determine the system tuned to the technical optimum. Before synthesizing the regulator and feedback, this time constant is set as a set requirement for the time of termination of the transient process. Thus, the formulation of an equation for the coefficients of the characteristic equation of the system is equated to the found equations and the unknown coefficients of the feedback and rcgulator are calculated from the resulting system equation. The practical applications of the obtained results can be limited with two conditions: it is assumed that the dynamically unstable systems under consideration are linear or linelized; the selected solutions and feedback elements are tactically feasible. The results obtained after applying the proposed technique allow to conclude that by changing the ratio between the values of the adjustable coefficients, the performance is increased by about two times. At the same time, the overshoot does not exceed 6 %, which is normalized by the conditions of the technical optimum. [ABSTRACT FROM AUTHOR]

Current methods for the classification of number fields with small regulator depend mainly on an upper bound for the discriminant, which can be improved by looking for the best possible upper bound of a specific polynomial function over a hypercube. In this paper, we provide new and effective upper bounds for the case of fields with one complex embedding and degree between five and nine: this is done by adapting the strategy we have adopted to study the totally real case, but for this new setting several new computational issues had to be overcome. As a consequence, we detect the four number fields of signature (r_1,r_2)=(6,1) with smallest regulator; we also expand current lists of number fields with small regulator in signatures (3,1), (4,1) and (5,1). [ABSTRACT FROM AUTHOR]

To cope with a high-salinity environment, haloarchaea generally employ the twin-arginine translocation (Tat) pathway to transport secretory proteins across the cytoplasm membrane in a folded state, including Tat-dependent extracellular subtilases (halolysins) capable of autocatalytic activation. Some halolysins, such as SptA of Natrinema gari J7-2, are produced at late-log phase to prevent premature enzyme activation and proteolytic damage of cellular proteins in haloarchaea; however, the regulation mechanism for growth phase-dependent expression of halolysins remains largely unknown. In this study, a DNA-protein pull-down assay was performed to identify the proteins binding to the 5'-flanking sequence of sptA encoding halolysin SptA in strain J7-2, revealing a TrmBL2-like transcription factor (NgTrmBL2). The ΔtrmBL2 mutant of strain J7-2 showed a sharp decrease in the production of SptA, suggesting that NgTrmBL2 positively regulates sptA expression. The purified recombinant NgTrmBL2 mainly existed as a dimer although monomeric and higher-order oligomeric forms were detected by native-PAGE analysis. The results of electrophoretic mobility shift assays (EMSAs) showed that NgTrmBL2 binds to the 5'-flanking sequence of sptA in a nonspecific and concentration-dependent manner and exhibits an increased DNA-binding affinity with the increase in KCl concentration. Moreover, we found that a distal cisregulatory element embedded in the neighboring upstream gene negatively regulates trmBL2 expression and thus participates in the growth phase-dependent biosynthesis of halolysin SptA. [ABSTRACT FROM AUTHOR]

Methanogenic archaea play a key role in the global carbon cycle because these microorganisms remineralize organic compounds in various anaerobic environments. The microorganism Methanosarcina barkeri is a metabolically versatile methanogen, which can utilize acetate, methanol, and H2/CO2 to synthesize methane. However, the regulatory mechanisms underlying methanogenesis for different substrates remain unknown. In this study, RNA-seq analysis was used to investigate M. barkeri growth and gene transcription under different substrate regimes. According to the results, M. barkeri showed the best growth under methanol, followed by H2/CO2 and acetate, and these findings corresponded well with the observed variations in genes transcription abundance for different substrates. In addition, we identified a novel regulator, MSBRM_RS03855 (designated as HdrR), which specifically activates the transcription of the heterodisulfide reductase hdrBCA operon in M. barkeri. HdrR was able to bind to the hdrBCA operon promoter to regulate transcription. Furthermore, the structural model analyses revealed a helix-turn-helix domain, which is likely involved in DNA binding. Taken together, HdrR serves as a model to reveal how certain regulatory factors control the expression of key enzymes in the methanogenic pathway. [ABSTRACT FROM AUTHOR]

Simple Summary: Crosstalk regulation is a common regulatory phenomenon in Streptomyces, typically mediated by regulatory factors within gene clusters. Utilizing these regulatory factors to enhance the production of target compounds represents an important approach. This study focuses on two regulatory factors, PteF and PteR, within the filipin gene cluster in Streptomyces avermitilis, investigating their effects on both avermectin production and overall cellular metabolism. The findings provide theoretical groundwork for constructing high-yielding engineered strains of avermectins and provide new insights into the role of PteF in the biosynthesis of avermectins and its impact on cellular metabolic processes. Crosstalk regulation is widespread in Streptomyces species. Elucidating the influence of a specific regulator on target biosynthetic gene clusters (BGCs) and cell metabolism is crucial for strain improvement through regulatory protein engineering. PteF and PteR are two regulators that control the biosynthesis of filipin, which competes for building blocks with avermectins in Streptomyces avermitilis. However, little is known about the effects of PteF and PteR on avermectin biosynthesis. In this study, we investigated their impact on avermectin biosynthesis and global cell metabolism. The deletion of pteF resulted in a 55.49% avermectin titer improvement, which was 23.08% higher than that observed from pteR deletion, suggesting that PteF plays a more significant role in regulating avermectin biosynthesis, while PteF hardly influences the transcription level of genes in avermectin and other polyketide BGCs. Transcriptome data revealed that PteF exhibited a global regulatory effect. Avermectin production enhancement could be attributed to the repression of the tricarboxylic acid cycle and fatty acid biosynthetic pathway, as well as the enhancement of pathways supplying acyl-CoA precursors. These findings provide new insights into the role of PteF on avermectin biosynthesis and cell metabolism, offering important clues for designing and building efficient metabolic pathways to develop high-yield avermectin-producing strains. [ABSTRACT FROM AUTHOR]

BACKGROUND: Cell death and neuroinflammation are two important targets in the treatment of spinal cord injury. Pyroptosis is a programmed cell death closely related to neuroinflammation and targeted inhibition of pyroptosis after spinal cord injury is a promising therapeutic strategy. OBJECTIVE: To summarize the molecular mechanism, positive and negative regulatory factors and therapeutic strategies of pyroptosis in spinal cord injury. METHODS: The search terms were “spinal cord injury, pyroptosis, nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3), Caspase, Gasdermin D (GSDMD), IL-1β, IL-18” and 93 English literatures included in PubMed and Web of Science were finally selected for review. RESULTS AND CONCLUSION: As a newly discovered programmed cell death, pyroptosis has been shown to play an important role in the secondary injury stage after spinal cord injury. Among the regulatory factors of pyroptosis after spinal cord injury, CD73, NRF2, GDF-11, dopamine, FANCC and miR-423-5P could inhibit pyroptosis, while TLR4 and Aopps could promote pyroptosis. In terms of treatment, the active ingredients of traditional Chinese medicine (paeonol, tripterine, betulinic acid, piperine, kaempferol, and camptothecin), exosomes of various cell origins, and some drugs (metformin, topotecan, lithium, zinc, and carbon monoxide-releasing molecule 3) can effectively inhibit pyroptosis and reduce secondary spinal cord injury, but the toxicity and specific dose of these drugs need to be further studied. The specific molecular mechanism by which pyroptosis aggravates spinal cord injury is still poorly understood. The role of non-classical pathways and other inflammasomes is worth further exploration. At present, the research on pyroptosis after spinal cord injury only stays at the animal experiment stage. There are no related clinical studies and no approved targeted therapeutic drugs. (6) The application of pyroptosis after spinal cord injury has great potential, and its specific regulatory mechanism should be further studied in the future to provide a new target for the treatment of spinal cord injury. [ABSTRACT FROM AUTHOR]

The oleaginous yeast, Lipomyces starkeyi can have diverse industrial applications due to its remarkable capacity to use various carbon sources for the biosynthesis intracellular triacylglycerides (TAGs). In L. starkeyi , TAG synthesis is enhanced through upregulation of genes involved in citrate-mediated acyl-CoA synthesis and Kennedy pathways through the transcriptional regulator LsSpt23p. High expression of LsSPT23 can considerably enhance TAG production. Altering the regulatory factors associated with lipid production can substantially augment lipid productivity. In this study, we identified and examined the L. starkeyi homolog sucrose nonfermenting 1 SNF1 (LsSNF1) of YlSNF1 , which encodes a negative regulator of lipid biosynthesis in the oleaginous yeast Yarrowia lipolytica. The deletion of LsSNF1 enhanced TAG productivity in L. starkeyi , suggesting that LsSnf1p is a negative regulator in TAG production. The enhancement of TAG production following deletion of LsSNF1 can primarily be attributed to the upregulation of genes in the citrate-mediated acyl-CoA synthesis and Kennedy pathways, pivotal routes in TAG biosynthesis. The overexpression of LsSPT23 enhanced lipid productivity; strain overexpressing LsSPT23 and without LsSNF1 exhibited increased TAG production capacity per cell. LsSnf1p also has a significant role in the utilization of carbon sources, including xylose or glycerol, in L. starkeyi. Our study results elucidated the role of LsSnf1p in the negative regulation of TAG synthesis in L. starkeyi , which has not previously been reported. • Lipomyces starkeyi SNF1 homolog (LsSNF1) was identified and the LsSNF1 deletion mutant was constructed. • LsSnf1p had important roles in lipid production and carbon-source utilization in L. starkeyi. • The overexpression of LsSpt23p and without LsSnf1p exhibited increased TAG production capacity per cell. [ABSTRACT FROM AUTHOR]

There is divalent magnesium and calcium ions existed in seawater. Under alkaline conditions, magnesium and calcium ions would react with hydroxide ions to generate insoluble hydroxyl complexes or hydroxide precipitates. In flotation process, the hydrophilic substances and collectors compete for adsorption on the surface of minerals, thereby reducing the floatability of minerals. In this study, the effects of seawater on the flotation separation of sphalerite from pyrite were investigated. The results show that under strong alkaline conditions, seawater has significant adverse effects on the flotation separation. Flotation regulators such as ethylenediamine tetraacetic acid, sodium hexametaphosphate, and sodium silicate can eliminate the adverse effect to a certain extent. The mechanisms were revealed through micro-flotation experiments, contact angle measurements, zeta potential measurements, XPS analysis and FT-IR analysis. [ABSTRACT FROM AUTHOR]

As a parameter to measure wettability, wetting heat change occurs when the interface substitution happened. There are few researches on the relationship between coal flotation and wetting heat. The wetting heat is the key variable that determines wettability. Calorimeter is a reliable means to measure the wetting heat. In this study, the heat flow during the wetting process of ultrafine coal particles was measured by calorimetry (UCP). The contact angle of the samples was determined by a contact angle meter. These wettability indexes were then related to the flotation response as determined by micro-flotation tests. The effects of regulators on the wettability of UCP were analyzed. It was found that there was a positive correlation between wetting heat reduction and flotation combustible recovery. The variance in the contact angle induced by regulators was also a factor affecting the flotation response. Results indicated that the wettability interpreted by wetting heat and contact angle is an excellent indicator for the flotation response of UCP. This research will help to understand the relationship between wettability and UCP flotation response. The research provided considerable regulators for improving UCP flotation. [ABSTRACT FROM AUTHOR]

An algebraic integer is said large if all its real or complex embeddings have absolute value larger than 1. An integral ideal is said large if it admits a large generator. We investigate the notion of largeness, relating it to some arithmetic invariants of the field involved, such as the regulator and the covering radius of the lattice of units. We also study its connection with the Weil height and the Bogomolov property. We provide an algorithm for testing largeness and give some applications to the construction of floor functions arising in the theory of continued fractions. [ABSTRACT FROM AUTHOR]

The purpose of the research was to assess the legitimacy of the establishment and functioning of the regulator (PGW Wody Polskie), responsible for approving tariffs for water supply and sewage disposal. Answers were sought as to the sense of its functioning and whether the tasks entrusted to it are performed properly. The main research method used in this study was a document survey consisting of a quantitative and qualitative analysis of the content contained. A review of available documents on the subject matter addressed was carried out. tMoreover, he opinion of local government officials and water and sewer entrepreneurs themselves on the functioning of PGW Wody Polskie was read. The author considers whether it is not better to return to the approval of tariffs at the level of municipal councils, as was the case before the amendment of the law. A thesis is put forward relating to the current way in which the regulator approves tariffs for the supply of municipal water and sewage by paying attention to the political issues of decision-making in this regard. [ABSTRACT FROM AUTHOR]

Biofilms are common living states for microorganisms, allowing them to adapt to environmental changes. Numerous Bacillus strains can form complex biofilms that play crucial roles in biocontrol processes. However, our current understanding of the molecular mechanisms of biofilm formation in Bacillus is mainly based on studies of Bacillus subtilis. Knowledge regarding the biofilm formation of other Bacillus species remains limited. In this study, we identified a novel transcriptional regulator, BmfR, belonging to the GntR family, that regulates biofilm formation in marine-derived Bacillus methylotrophicus B-9987. We demonstrated that BmfR induces biofilm formation by activating the extracellular polysaccharide structural genes epsA-O and negatively regulating the matrix gene repressor, SinR; of note it positively affects the expression of the master regulator of sporulation, Spo0A. Furthermore, database mining for BmfR homologs has revealed their widespread distribution among many bacterial species, mainly Firmicutes and Proteobacteria. This study advances our understanding of the biofilm regulatory network of Bacillus strains, and provides a new target for exploiting and manipulating biofilm formation. [ABSTRACT FROM AUTHOR]

In the era of stem cell research and regenerative medicine, understanding the regulatory networks that drive cellular reprogramming is fundamental. The study entitled "Cross-lineage potential of Ascl1 uncovered by comparing diverse reprogramming regulatomes" published in Stem Cell Reports sheds light on the remarkable versatility of Ascl1, a transcription factor known for its pivotal role in neurogenesis. By comparing regulatomes across multiple cell lineages, the authors have elucidated the potential of Ascl1 to facilitate the conversion of non-neural cells into various lineages beyond its canonical neural fate, suggesting its potential as a master regulator for lineage reprogramming. These observations challenge our current understanding of cell fate determination and open exciting avenues for regenerative medicine. [ABSTRACT FROM AUTHOR]

This work presents a fully integrated mixed-mode low-dropout voltage regulator that achieves a fast transient response by utilizing two feedback mechanisms. The first feedback mechanism is the conventional analog regulation that includes an operational amplifier. The second feedback mechanism is based on digitizing any fast change in the output voltage using multiple comparators and subsequently enabling either an NMOS-based or a PMOS-based current DAC. The DAC provides current in opposite polarity to the sharp transient change in load current. As a result, addressing sharp changes in load current is not limited by the gain–bandwidth product of the error amplifier. The LDO was implemented using 180-nm CMOS technology devices. It uses a supply voltage input range of 1.6–2 V and produces an output voltage of 1.2 V. In simulations, the LDO regulator achieves 143- μ A quiescent current, − 56-dB PSRR @ 1-kHz noise frequency and an output voltage drop of around 200 mV for a load current step of 100 mA. The LDO can provide a maximum load current of 200 mA. [ABSTRACT FROM AUTHOR]

Flowering is the transition process from vegetative to reproductive growth determined by many endogenous and exogenous factors. Nitrogen (N), as a dominant macronutrient for plant growth, can largely affect flowering time. A complex network integrates multiple environmental signals consisting of N status and photoperiod condition into internal regulation of flowering time in plants. So far, several transcription factors, kinases, N transporters and N assimilation enzymes have been identified to participate in the N-dependent regulation of flowering time. In this review, we summarize prominent mechanisms and key players that govern the N-dependent response of flowering time, and further discuss the interaction between N utilization and growth phase transitions in plants. Since the impact of N status on flowering time varies over plant species and shows large genetic diversities, we focus on current state of knowledge on regulatory pathways of N-determined flowering time in Arabidopsis and graminaceous plants, especially in rice. These understanding of the N-dependent flowering response can provide valuable inspirations and novel strategies to coordinate growth period with N availability for improving N use efficiency and crop productivity. [ABSTRACT FROM AUTHOR]

Microbial communities enmeshed in a matrix of macromolecules, termed as biofilms, are the natural setting of bacteria. Exopolysaccharide is a critical matrix component of biofilms. Here, we focus on biofilm matrix exopolysaccharides in Pseudomonas aeruginosa. This opportunistic pathogen can adapt to a wide range of environments and can form biofilms or aggregates in a variety of surfaces or environments, such as the lungs of people with cystic fibrosis, catheters, wounds, and contact lenses. The ability to synthesize multiple exopolysaccharides is one of the advantages that facilitate bacterial survival in different environments. P. aeruginosa can produce several exopolysaccharides, including alginate, Psl, Pel, and lipopolysaccharide. In this review, we highlight the roles of each exopolysaccharide in P. aeruginosa biofilm development and how bacteria coordinate the biosynthesis of multiple exopolysaccharides and bacterial motility. In addition, we present advances in antibiofilm strategies targeting matrix exopolysaccharides, with a focus on glycoside hydrolases. [ABSTRACT FROM AUTHOR]

Microbial communities enmeshed in a matrix of macromolecules, termed as biofilms, are the natural setting of bacteria. Exopolysaccharide is a critical matrix component of biofilms. Here, we focus on biofilm matrix exopolysaccharides in Pseudomonas aeruginosa. This opportunistic pathogen can adapt to a wide range of environments and can form biofilms or aggregates in a variety of surfaces or environments, such as the lungs of people with cystic fibrosis, catheters, wounds, and contact lenses. The ability to synthesize multiple exopolysaccharides is one of the advantages that facilitate bacterial survival in different environments. P. aeruginosa can produce several exopolysaccharides, including alginate, Psl, Pel, and lipopolysaccharide. In this review, we highlight the roles of each exopolysaccharide in P. aeruginosa biofilm development and how bacteria coordinate the biosynthesis of multiple exopolysaccharides and bacterial motility. In addition, we present advances in antibiofilm strategies targeting matrix exopolysaccharides, with a focus on glycoside hydrolases. [ABSTRACT FROM AUTHOR]

Toll-like receptor 8 (TLR8), an important innate immune receptor recognizing single stranded RNA and the antiviral imidazoquinoline compounds, can activate intracellular signaling pathway and produce an inflammatory response to kill and eliminate pathogens. However, the molecular regulation mechanisms of TLR8 signaling and its anti-infection activity are not fully elucidated. Our previous transcriptome analysis of porcine TLR8 (pTLR8) signaling suggested the immune checkpoint receptor TIM-3 as the potential regulator for pTLR8. Here we investigated TIM-3 in the regulation of pTLR8 signaling and its anti-infection activity. Our results showed that porcine TIM-3 is upregulated by pTLR8 signaling and TIM-3 inhibits pTLR8 signaling activity in a negative feedback way. Accordingly, TIM-3 disturbs pTLR8 mediated anti-bacterial and anti-viral activity. Mechanistically, TIM-3 suppresses PI3K-AKT pathway by inhibiting the TLR8-PI3K p85 interaction and subsequent AKT phosphorylation which is essential for TLR8 signaling and anti-infection activity. Therefore, our study reveals new insights into innate immune TLR8 signaling and its anti-infection function. [ABSTRACT FROM AUTHOR]

Theft of electricity is a significant loss of power sources. This fraud is mostly attributed to users' actions such as removing the power supply, misuse of the power supply, etc. This analysis provides a way to handle the bypass and abuse of energy meters. A detection method of disconnection of low voltage anti-theft transformer (DM-DLVATT) to detect electricity theft is proposed in this research. The device architecture on a designed microcontroller's measurement of two sensors. Although one of the new sensors controls the consumer charge's power, the consumer has mounted the energy consumed by all modules while maintaining the device. The robbery suggests some difference between the interpreted values. There is also a temporary adjustment in the meter to restart the meter until it is altered. To recharge power products and track carbon emissions, the consumer often has remote access to electricity monitors. The device has been calculated correctly, and any effort has been made to circumvent or modify the voltage regulator. Finally, all disreputable actions using GSM technologies have been registered. [ABSTRACT FROM AUTHOR]

The Agency for the Cooperation of Energy Regulators (acer) was launched in 2011 to contribute to the establishment and functioning of the eu's internal energy market. This study aims to evaluate acer's success in establishing and ensuring the functioning of the internal energy market, both from acer's and its stakeholders' (energy regulators and energy traders in the eu member states) perspective. The paper includes the results of interviews with nine national regulatory authorities (nras) and ten energy traders fromthe eu member states. This research revealed that, based on their perception, acer is actually crucial for the operation of the internal market. In addition, nras and energy traders mostly agree that the eu has a nearly functional internal energy market and that acer is vitally important for the functioning of the internal market. [ABSTRACT FROM AUTHOR]

The assessment of ecosystem services provides an intuitive source of information on the benefits humans derive from ecosystems. The equivalent factor method was applied to calculate the ecosystem service value (ESV) in combination with net primary productivity (NPP) calculated by the process-based Carnegie–Ames–Stanford approach (CASA) model. This study evaluated grassland ESV and its spatial evolution characteristics in China from 2001 to 2020 and revealed the impact of climate factors. For 2001–2020, the annual grassland ESV ranged from 1.17 × 1012 to 1.51 × 1012 yuan (renminbi, China yuan—the same below; $0.15 × 1012–$0.20 × 1012, US dollar), with an average of 1.37 × 1012 yuan ($0.18 × 1012). The spatial pattern of ESV per unit area of grassland was notably characterized by an increase from northwest to southeast. However, the value of grassland ecosystem services was relatively large (exceeding 10 × 106 yuan; $1.30 × 106) in northern and western provinces and was the lowest (less than 0.2 × 106 yuan; $0.03 × 106) in eastern and southern provinces. In the last 20 years, grassland ESV has increased in most areas of China and has decreased only in some western and northern areas. Compared with the first 10 years, the average ESV of grassland in most areas increased in the last 10 years, usually by less than 20%. However, it decreased in the western and northern parts of China, mainly concentrated in the alpine meadow and alpine grassland of the Qinghai–Tibet Plateau and the grassland around the Yili region of Xinjiang. Precipitation was the main regulating factor of grassland ESV and had a positive impact in 79% grassland areas, especially in northern China. Evapotranspiration and sunshine hours exhibited a marginal impact on ESV, but temperature and relative humidity had no significant effect. Overall, this study contributes to exploring the spatiotemporal patterns of grassland ecosystem service value and the impact of climate factors in China, thereby providing reliable guidance for grassland ecosystem management. [ABSTRACT FROM AUTHOR]

Background: Amyotrophic lateral sclerosis (ALS) is a complex, late-onset, neurodegenerative disease with a genetic contribution to disease liability. Genome-wide association studies (GWAS) have identified ten risk loci to date, including the TNIP1/GPX3 locus on chromosome five. Given association analysis data alone cannot determine the most plausible risk gene for this locus, we undertook a comprehensive suite of in silico, in vivo and in vitro studies to address this. Methods: The Functional Mapping and Annotation (FUMA) pipeline and five tools (conditional and joint analysis (GCTA-COJO), Stratified Linkage Disequilibrium Score Regression (S-LDSC), Polygenic Priority Scoring (PoPS), Summary-based Mendelian Randomisation (SMR-HEIDI) and transcriptome-wide association study (TWAS) analyses) were used to perform bioinformatic integration of GWAS data (Ncases = 20,806, Ncontrols = 59,804) with 'omics reference datasets including the blood (eQTLgen consortium N = 31,684) and brain (N = 2581). This was followed up by specific expression studies in ALS case-control cohorts (microarray Ntotal = 942, protein Ntotal = 300) and gene knockdown (KD) studies of human neuronal iPSC cells and zebrafish-morpholinos (MO). Results: SMR analyses implicated both TNIP1 and GPX3 (p < 1.15 × 10−6), but there was no simple SNP/expression relationship. Integrating multiple datasets using PoPS supported GPX3 but not TNIP1. In vivo expression analyses from blood in ALS cases identified that lower GPX3 expression correlated with a more progressed disease (ALS functional rating score, p = 5.5 × 10−3, adjusted R2 = 0.042, Beffect = 27.4 ± 13.3 ng/ml/ALSFRS unit) with microarray and protein data suggesting lower expression with risk allele (recessive model p = 0.06, p = 0.02 respectively). Validation in vivo indicated gpx3 KD caused significant motor deficits in zebrafish-MO (mean difference vs. control ± 95% CI, vs. control, swim distance = 112 ± 28 mm, time = 1.29 ± 0.59 s, speed = 32.0 ± 2.53 mm/s, respectively, p for all < 0.0001), which were rescued with gpx3 expression, with no phenotype identified with tnip1 KD or gpx3 overexpression. Conclusions: These results support GPX3 as a lead ALS risk gene in this locus, with more data needed to confirm/reject a role for TNIP1. This has implications for understanding disease mechanisms (GPX3 acts in the same pathway as SOD1, a well-established ALS-associated gene) and identifying new therapeutic approaches. Few previous examples of in-depth investigations of risk loci in ALS exist and a similar approach could be applied to investigate future expected GWAS findings. [ABSTRACT FROM AUTHOR]

Background: Bioconversion of levoglucosan, a promising sugar derived from the pyrolysis of lignocellulose, into biofuels and chemicals can reduce our dependence on fossil-based raw materials. However, this bioconversion process in microbial strains is challenging due to the lack of catalytic enzyme relevant to levoglucosan metabolism, narrow production ranges of the native strains, poor cellular transport rate of levoglucosan, and inhibition of levoglucosan metabolism by other sugars co-existing in the lignocellulose pyrolysate. The heterologous expression of eukaryotic levoglucosan kinase gene in suitable microbial hosts like Escherichia coli could overcome the first two challenges to some extent; however, no research has been dedicated to resolving the last two issues till now. Results: Aiming to resolve the two unsolved problems, we revealed that seven ABC transporters (XylF, MalE, UgpB, UgpC, YtfQ, YphF, and MglA), three MFS transporters (KgtP, GntT, and ActP), and seven regulatory proteins (GalS, MhpR, YkgD, Rsd, Ybl162, MalM, and IraP) in the previously engineered levoglucosan-utilizing and ethanol-producing E. coli LGE2 were induced upon exposure to levoglucosan using comparative proteomics technique, indicating these transporters and regulators were involved in the transport and metabolic regulation of levoglucosan. The proteomics results were further verified by transcriptional analysis of 16 randomly selected genes. Subsequent gene knockout and complementation tests revealed that ABC transporter XylF was likely to be a levoglucosan transporter. Molecular docking showed that levoglucosan can bind to the active pocket of XylF by seven H-bonds with relatively strong strength. Conclusion: This study focusing on the omics discrepancies between the utilization of levoglucosan and non-levoglucosan sugar, could provide better understanding of levoglucosan transport and metabolism mechanisms by identifying the transporters and regulators related to the uptake and regulation of levoglucosan metabolism. The protein database generated from this study could be used for further screening and characterization of the transporter(s) and regulator(s) for downstream enzymatic/genetic engineering work, thereby facilitating more efficient microbial utilization of levoglucosan for biofuels and chemicals production in future. [ABSTRACT FROM AUTHOR]

The Fan‐Led Review of Football Governance, chaired by Tracey Crouch MP, has recently been published and makes forty‐seven recommendations in relation to the professional game in England. The core recommendations are: the creation of an independent regulator; more scrutiny of ownership and directors; financial review and redistribution; governance over issues of history and heritage; fan consultation; golden shares; parity for women's football; diversity and player welfare. The report has led to a lukewarm response from football authorities and clubs, but has been welcomed by fans and commentators. [ABSTRACT FROM AUTHOR]

This article argues that in qualitative research into the work of a regulator, it is as important to watch out for that regulator's omissions and silences as it is to examine what the regulator does and says. The argument is illustrated by data drawn from a study of the Independent Custody Visiting Scheme, the purpose of which is (or should be) to safeguard detainees and to deter police from misconduct which might lead to deaths in custody. Research into the scheme included using the technique of watching out for what the visitors did not do and did not say. The data obtained by this method are interpreted through the lens of Lukes' theory of power to suggest that this watchdog has been debarked as a result of the power of the police. [ABSTRACT FROM AUTHOR]

The article considers the option of improving the automatic control systems for natural gas combustion as a fuel for boilers. The aim of the improvement is to optimize the gas-air ratio to maintain the set temperature in the heated rooms, depending on the ambient temperature. In most of the currently used hot water boilers, the gas / air ratio is maintained in accordance with the regime maps without taking into account the economic and environmental combustion of gas, without automatically taking into account the ambient temperature. The desire to reduce excess fuel consumption necessitates the creation of automatic control systems that would maintain the required temperature of the coolant at the boiler outlet at different ambient temperatures. The main principle of increasing efficiency is the maximum possible use of available (lower) heat of combustion QnP. The main components of losses of warmth at the same time are losses with q2 flue gases and losses from so incomplete combustion of q3 fuel. The amount of harmful emissions into the atmosphere depends of both of these indicators that are closely related to the coefficient of excess air α in the burning fuel flare. The paper analyzes several types of fuel-air ratio control systems, notes their advantages and disadvantages. It is con-cluded that the greatest positive effect can be achieved only with the use of systems of continuous automatic control and regulation of the fuel-air ratio. The article proposes the structure of the control system that moni-tors the ambient temperature and changes the temperature at the boiler outlet accordingly. At the same time, in order to be able to operate the system in a significant range of ambient temperatures and maintain economical fuel combustion, the use of adaptive PID controllers is proposed on the basis of tabular changes in their set-tings. To ensure environmentally friendly fuel combustion, a "rebound" mode is used. The simulation of tem-perature change in the control system showed the possibility of its practical for house heating systems with low-power boilers. [ABSTRACT FROM AUTHOR]

• Companies are increasingly seeking HTA insights from stakeholders during development. • We examined companies' strategies for seeking HTA-related scientific advice. • Single HTA agency advice was most frequently used, particularly from G-BA and NICE. • HTA advice tended to focus on efficacy/effectiveness evaluation and trial design. • Parallel scientific advice was the most influential on development programmes. There is a growing trend for pharmaceutical companies to seek scientific advice on drug development from a Health Technology Assessment (HTA) perspective, to improve the efficiency of their studies, enable better trial design, and support the goals of positive HTA recommendation for reimbursement. This study uses information collected directly from companies on individual products to assess their strategies and practices for seeking HTA-related scientific advice in terms of which stakeholders to engage and for what purpose, when to seek scientific advice, and whether to implement that advice within global clinical development. [ABSTRACT FROM AUTHOR]

In this study, comprehensive analyses were performed to determine the function of an atypical MarR homolog in Achromobacter sp. strain As-55. Genomic analyses of Achromobacter sp. As-55 showed that this marR is located adjacent to an arsV gene. ArsV is a flavin-dependent monooxygenase that confers resistance to the antibiotic methylarsenite [MAs(III)], the organoarsenic compound roxarsone(III) [Rox (III)], and the inorganic antimonite [Sb(III)]. Similar marR genes are widely distributed in arsenic-resistant bacteria. Phylogenetic analyses showed that these MarRs are found in operons predicted to be involved in resistance to inorganic and organic arsenic species, so the subfamily was named MarRars. MarRars orthologs have three conserved cysteine residues, which are Cys36, Cys37, and Cys157 in Achromobacter sp. As-55, mutation of which compromises the response to MAs(III)/Sb(III). GFP-fluorescent biosensor assays show that AdMarRars (MarR protein of Achromobacter deleyi As-55) responds to trivalent As(III) and Sb(III) but not to pentavalent As(V) or Sb(V). The results of RT-qPCR assays show that arsV is expressed constitutively in a marR deletion mutant, indicating that marR represses transcription of arsV. Moreover, electrophoretic mobility shift assays (EMSAs) demonstrate that AdMarRars binds to the promoters of both marR and arsV in the absence of ligands and that DNA binding is relieved upon binding of As(III) and Sb(III). Our results demonstrate that AdMarRars is a novel As(III)/Sb(III)-responsive transcriptional repressor that controls expression of arsV, which confers resistance to MAs(III), Rox(III), and Sb(III). AdMarRars and its orthologs form a subfamily of MarR proteins that regulate genes conferring resistance to arsenic-containing antibiotics. [ABSTRACT FROM AUTHOR]

Shigella is an intracellular pathogen that primarily infects the human colon and causes shigellosis. Shigella virulence relies largely on the type III secretion system (T3SS) and secreted effectors. VirF, the master Shigella virulence regulator, is essential for the expression of T3SS-related genes. In this study, we found that YhjC, a LysR-type transcriptional regulator, is required for Shigella virulence through activating the transcription of virF. Pathogenicity of the yhjC mutant, including colonization in the colons of guinea pigs as well as its ability for host cell adhesion and invasion, was significantly lowered. Expression levels of virF and nearly all VirF-dependent genes were downregulated by yhjC deletion, indicating that YhjC can activate virF transcription. Electrophoretic mobility shift assay analysis demonstrated that YhjC could bind directly to the virF promoter region. Therefore, YhjC is a novel virulence regulator that positively regulates the virF expression and promotes Shigella virulence. Additionally, genome-wide expression analysis identified the presence of other genes in the large virulence plasmid and a genome exhibiting differential expression in response to yhjC deletion, with 169 downregulated and 99 upregulated genes, indicating that YhjC also functioned as a global regulatory factor. [ABSTRACT FROM AUTHOR]

Background: Sepsis is a dysregulated host response to pathogens. Delay in sepsis diagnosis has become a primary cause of patient death. This study determines some factors to prevent septic shock in its early stage, contributing to the early treatment of sepsis. Methods: The sequencing data (RNA- and miRNA-sequencing) of patients with septic shock were obtained from the NCBI GEO database. After re-annotation, we obtained lncRNAs, miRNA, and mRNA information. Then, we evaluated the immune characteristics of the sample based on the ssGSEA algorithm. We used the WGCNA algorithm to obtain genes significantly related to immunity and screen for important related factors by constructing a ceRNA regulatory network. Result: After re-annotation, we obtained 1708 lncRNAs, 129 miRNAs, and 17 326 mRNAs. Also, through the ssGSEA algorithm, we obtained 5 important immune cells. Finally, we constructed a ceRNA regulation network associated with SS pathways. Conclusion: We identified 5 immune cells with significant changes in the early stage of septic shock. We also constructed a ceRNA network, which will help us explore the pathogenesis of septic shock. [ABSTRACT FROM AUTHOR]

Summary: Plant glandular secretory trichomes (GSTs) produce various specialized metabolites. Increasing GST density represents a strategy to enhance the yield of these chemicals; however, the gene regulatory network that controls GST initiation remains unclear.In a previous study of Artemisiaannua L., we found that a HD‐ZIP IV transcription factor, AaHD1, promotes GST initiation by directly regulating AaGSW2. Here, we identified two AaHD1‐interacting transcription factors, namely AaMIXTA‐like 2 (AaMYB16) and AaMYB5.Through the generation and characterization of transgenic plants, we found that AaMYB16 is a positive regulator of GST initiation, whereas AaMYB5 has the opposite effect. Notably, neither of them regulates GST formation independently. Rather, they act competitively, by interacting and modulating AaHD1 promoter binding activity. Additionally, the phytohormone jasmonic acid (JA) was shown to be associated with the AaHD1‐AaMYB16/AaMYB5 regulatory network through transcriptional regulation via a JASMONATE‐ZIM DOMAIN (JAZ) protein repressor.These results bring new insights into the mechanism of GST initiation through regulatory complexes, which appear to have similar functions in a range of vascular plant taxa. [ABSTRACT FROM AUTHOR]

Caenorhabditis elegans T09F3.2 is a homolog of the human mitochondrial pyrimidine nucleotide transporter. We isolated a T09F3.2 mutant (TOG2) with a 0.7 kb deletion in T09F3.2 , which exhibited low growth and movement. TOG2 worms exhibited high glucose content and low lipid content in intestinal cells and oocytes, suggesting glucose leakage from these cells. The glucose transport inhibitor phloretin improved the growth of TOG2 worms, suggesting that T09F3.2 regulates the phloretin-sensitive glucose transporter FGT-1. The localization of T09F3.2 was examined to assess the regulation of FGT-1 by T09F3.2. Distinct expression of T09F3.2 fused with DsRed-Monomer (T09F3.2:DsRed-Monomer) was observed in the basal domain of intestinal cells and was weakly expressed in many cells. Colocalization of FGT-1 and T09F3.2 was observed in the intestinal cell surface and body wall muscle. This colocalization supports the regulation of FGT-1 by T09F3.2. These results reveal new aspects of glucose transporter regulation. • Caenorhabditis elegans T09F3.2 is a homolog of pyrimidine nucleotide transporters. • T09F3.2 mutant exhibited slow growth and movement, which was improved by phloretin. • T09F3.2 colocalizes with phloretin-sensitive glucose transporter FGT-1. • T09F3.2 regulates glucose transporters. [ABSTRACT FROM AUTHOR]

DNA polymerase IV (pol IV) is expressed at increased levels in Escherichia coli cells that suffer DNA damage. In a recent live-cell single-molecule fluorescence microscopy study, we demonstrated that the formation of pol IV foci is strongly recB-dependent in cells treated with the DNA break-inducing antibiotic ciprofloxacin. The results of that study support a model in which pol IV acts to extend D-loop structures during recombinational repair of DNA double-strand breaks. In the present study, we extend upon this work, investigating the UmuD and UmuDʹ proteins as potential modulators of pol IV activity in ciprofloxacin-treated cells. We found that the non-cleavable mutant UmuD(K97A) promotes long-lived association of pol IV with the nucleoid, whereas its cleaved form, UmuDʹ, which accumulates in DNA-damaged cells, reduces binding. The results provide additional support for a model in which UmuD and UmuDʹ directly modulate pol IV-binding to the nucleoid. [ABSTRACT FROM AUTHOR]

Although better known as a pathogen of wheat stem bases, Fusarium pseudograminearum also causes Fusarium head blight. A natural isolate of F. pseudograminearum was identified that showed severely reduced virulence towards wheat heads and a map-based cloning approach was undertaken to identify the genetic basis of this phenotype. Using a population of 95 individuals, a single locus on chromosome 1 was shown to be responsible for the low virulence. Fine mapping narrowed the region to just five possible SNPs of which one was in the F. pseudograminearum homologue of velvet A. Knockout mutants of velvet A, which were non-pathogenic towards wheat, confirmed that velvet A regulates virulence in this pathogen. The mutation in velvet A was only found in a single field isolate and the origin of the mutation is unknown. •An isolate of F. pseudograminearum showed reduced virulence towards wheat heads. •Map-based cloning delimited the trait to a region on Chromosome 1. •Fine mapping narrowed the region to just 5 possible SNPs with one in velvet A. •Knockout mutants of velvet A, were non-pathogenic towards wheat. •The mutation in velvet A was only found in a single field isolate. [ABSTRACT FROM AUTHOR]

We prove a formula relating the Mahler measure of an infinite family of three-variable polynomials to a combination of the Riemann zeta function at s = 3 and special values of the Bloch–Wigner dilogarithm by evaluating a regulator. The evaluation requires two different applications of Jensen's formula and analyzing the integral in two different planes, as opposed to the more common strategy of using only one plane. The degrees of the monomials involving one of the variables are allowed to vary freely, leading to an interesting application of the Boyd–Lawton formula. [ABSTRACT FROM AUTHOR]

Ferroptosis is a newly proposed cell death mode in recent years, which is different from the traditional cell death mode, apoptosis, cell necrosis and autophagy. Its molecular characteristics include iron-dependent accumulation of lipid reactive oxygen species (ROS), mitochondrial morphological changes and damage to membrane permeability. In the nervous system, studies have found that it plays an important role in neurodegenerative diseases such as Parkinson's disease (PD) and Alzheimer's disease (AD) . With the further study on ferroptosis, it has been revealed that ferroptosis plays an important role in is chemic and hemorrhagic stroke and nervous system tumors. At present, the reviews on this aspect in China are relatively few. In this paper, the research progress in the mechanism of ferroptosis in nervous system tumors will be reviewed. [ABSTRACT FROM AUTHOR]

Shigella is an intracellular pathogen that primarily infects the human colon and causes shigellosis. Shigella virulence relies largely on the type III secretion system (T3SS) and secreted effectors. VirF, the master Shigella virulence regulator, is essential for the expression of T3SS-related genes. In this study, we found that YhjC, a LysR-type transcriptional regulator, is required for Shigella virulence through activating the transcription of virF. Pathogenicity of the yhjC mutant, including colonization in the colons of guinea pigs as well as its ability for host cell adhesion and invasion, was significantly lowered. Expression levels of virF and nearly all VirF-dependent genes were down-regulated by yhjC deletion, indicating that YhjC can activate virF transcription. Electrophoretic mobility shift assay analysis demonstrated that YhjC could bind directly to the virF promoter region. Therefore, YhjC is a novel virulence regulator that positively regulates the virF expression and promotes Shigella virulence. Additionally, genome-wide expression analysis identified the presence of other genes in the large virulence plasmid and a genome exhibiting differential expression in response to yhjC deletion, with 169 downregulated and 99 upregulated genes, indicating that YhjC also functioned as a global regulatory factor. [ABSTRACT FROM AUTHOR]

In this article, the formulation for the estimation of state variables in closed loop and open loop in a control system was initially presented; Next, the advantages and disadvantages that could arise when implementing either of the two models were shown and explained. Finally, as an application, the case of a hydraulic system was studied with which it is concluded on the importance of estimating the state variables of a system that it is desired to control. [ABSTRACT FROM AUTHOR]

This article proposes a bandgap reference (BGR) recursive low-dropout (LDO) regulator chip that achieves a high power supply rejection (PSR) in the low- to mid-frequency range. The presented LDO design enables the total PSR of LDO to be free from the finite ripple-rejection of the BGR circuit, resulting in low design complexity and low power consumption. To improve the PSR further, the gate buffer is modified to provide an additional ripple feedforward cancellation. The modified gate buffer also offers fast transient response and stable operation. Moreover, a light-load stabilizer loop is also suggested to provide high stability over all load conditions. A prototype chip able to supply up to 300 mA output current was implemented by 0.5-μm 5-V CMOS devices. The PSR was measured to be –102 to –80 dB at frequencies from 100 Hz to 0.1 MHz, which is higher than that of prior LDOs with COUT ≥ 1 μF. The proposed LDO consumes only 50 μA at a load current of 300 mA, and a peak current efficiency of 99.98% was achieved. The line and load regulations were measured as 0.003%/V and 0.28%/A, respectively. This chip shows a figure-of-merit of 11 ps in the transient response. [ABSTRACT FROM AUTHOR]

Microvibrations may affect the quality and yield of products in precision processes. Therefore, vibration control is essential for minimizing position errors and improving the quality of production. Conventional active vibration isolation systems (AVISs) do not consider the effect of inertia variation, such as the movement of the stage and manipulator, on the system. Variations in inertia are associated with rotational motion, and they require a change in the modeling of an AVIS. Owing to this change, the system may not be optimal and may become unstable because the gain value is close to the critical point of the system. This results in insufficient performance. To overcome these issues, in this study, active vibration isolation was evaluated with the aim of actively controlling an AVIS while considering the effect of inertia variation. The system used in this study consists of an adaptive linear quadratic Gaussian (LQG) controller with six degrees of freedom. The inertia of the entire system changes based on the position of a stage mover. This variation in inertia alters the model of the system. The model is updated using the LQG controller, and the performance of the controller is evaluated. The LQG controller is used to evaluate the followability and transmissibility of the AVIS. The feedback loop is analyzed using Nyquist plots to determine the correlation between inertia variation and robustness. As a result, the phase margin decreases to 40 ° or lower as the rate of inertia variation increases. When the model is updated, the Nyquist's path is included in the unit circle. The correlation between inertia variation and performance is analyzed using Bode plots. The correlation shows a difference of approximately 10 dB depending on whether the model is updated. • Effect of inertia change on an active vibration isolation system was analyzed. • Active vibration isolation system was controlled depending on inertia change. • Adaptive linear quadratic Gaussian controller was employed. • Relation between inertia and control performance was determined. • Controller performance is robust near the resonance frequency. [ABSTRACT FROM AUTHOR]

Acute gouty arthritis (AGA) is characterized by the accumulation of pro-inflammatory cytokines, which are immunological responses to monosodium urate (MSU) crystals. It has been demonstrated that long non-coding RNA (lncRNA)-MM2P is a novel regulator of M2 polarization of macrophages. The aim of the present study was to investigate whether lncRNA-MM2P regulates the MSU-induced inflammatory process. In cell models of RAW 264.7 and THP-1-derived macrophages, decreased expression of lncRNA-MM2P was observed in lipopolysaccharide- and MSU-treated macrophages, which was accompanied with obvious inflammatory responses. Using small interfering RNA to knockdown lncRNA-MM2P led to the upregulation of MSU-mediated inflammatory responses, both in RAW 264.7 and THP-1-derived macrophages. In conclusion, lncRNA-MM2P could be an important regulator of MSU-induced inflammation, and therefore could be involved in the development of AGA. [ABSTRACT FROM AUTHOR]

We consider a functional relation between a given Wilsonian renormalization group (RG) flow, which has to be related to a specific coarse-graining procedure, and an infinite family of (UV cutoff) scale-dependent field redefinitions. Within this framework, one can define a family of Wilsonian proper-time (PT) exact RG equations associated to an arbitrary regulator function. New applications of these RG flow schemes to the Ising Universality class in three dimensions in the derivative expansion are shortly illustrated. [ABSTRACT FROM AUTHOR]

When two or more bacterial species inhabit a shared niche, often, they must compete for limited nutrients. Iron is an essential nutrient that is especially scarce in the marine environment. Bacteria can use the production, release, and re‐uptake of siderophores, small molecule iron chelators, to scavenge iron. Siderophores provide fitness advantages to species that employ them by enhancing iron acquisition, and moreover, by denying iron to competitors incapable of using the siderophore–iron complex. Here, we show that cell‐free culture fluids from the marine bacterium Vibrio fischeri ES114 prevent the growth of other vibrio species. Mutagenesis reveals the aerobactin siderophore as the inhibitor. Our analysis reveals a gene, that we name aerE, encodes the aerobactin exporter, and LuxT is a transcriptional activator of aerobactin production. In co‐culture, under iron‐limiting conditions, aerobactin production allows V. fischeri ES114 to competitively exclude Vibrio harveyi, which does not possess aerobactin production and uptake genes. In contrast, V. fischeri ES114 mutants incapable of aerobactin production lose in competition with V. harveyi. Introduction of iutA, encoding the aerobactin receptor, together with fhuCDB, encoding the aerobactin importer are sufficient to convert V. harveyi into an "aerobactin cheater." [ABSTRACT FROM AUTHOR]

This study addressed the functionality of genetic circuits carrying natural regulatory elements of Clostridium acetobutylicum ATCC 824 in the presence of the respective inducer molecules. Specifically, promoters and their regulators involved in diverse carbon source utilization were characterized using mCherryOpt or beta-galactosidase as a reporter. Consequently, most of the genetic circuits tested in this study were functional in Clostridium acetobutylicum ATCC 824 in the presence of an inducer, leading to the expression of reporter proteins. These genetic sensor-regulators were found to be transferable to another Clostridium species, such as Clostridium beijerinckii NCIMB 8052. The gradual expression of reporter protein was observed as a function of the carbohydrates of interest. A xylose-inducible promoter allows a titratable and robust expression of a reporter protein with stringency and efficacy. This xylose-inducible circuit was seen to enable induction of the expression of reporter proteins in the presence of actual sugar mixtures incorporated in woody hydrolysate wherein glucose and xylose are present as predominant carbon sources. [ABSTRACT FROM AUTHOR]

Fine-resolution differentiation trajectories of adult human hematopoietic stem cells (HSCs) involved in the generation of red cells is critical for understanding dynamic developmental changes that accompany human erythropoiesis. Using single-cell RNA sequencing (scRNA-seq) of primary human terminal erythroid cells (CD34-CD235a+) isolated directly from adult bone marrow (BM) and umbilical cord blood (UCB), we documented the transcriptome of terminally differentiated human erythroblasts at unprecedented resolution. The insights enabled us to distinguish polychromatic erythroblasts (PolyEs) at the early and late stages of development as well as the different development stages of orthochromatic erythroblasts (OrthoEs). We further identified a set of putative regulators of terminal erythroid differentiation and functionally validated three of the identified genes, AKAP8L, TERF2IP, and RNF10, by monitoring cell differentiation and apoptosis. We documented that knockdown of AKAP8L suppressed the commitment of HSCs to erythroid lineage and cell proliferation and delayed differentiation of colony-forming unit-erythroid (CFU-E) to the proerythroblast stage (ProE). In contrast, the knockdown of TERF2IP and RNF10 delayed differentiation of PolyE to OrthoE stage. Taken together, the convergence and divergence of the transcriptional continuums at single-cell resolution underscore the transcriptional regulatory networks that underlie human fetal and adult terminal erythroid differentiation. [ABSTRACT FROM AUTHOR]

The Agency for the Cooperation of Energy Regulators (acer) was launched in 2011 to contribute to the establishment and functioning of the eu's internal energy market. This study aims to evaluate acer's success in establishing and ensuring the functioning of the internal energy market, both from acer's and its stakeholders' (energy regulators and energy traders in the eu member states) perspective. The paper includes the results of interviews with nine national regulatory authorities (nras) and ten energy traders fromthe eu member states. This research revealed that, based on their perception, acer is actually crucial for the operation of the internal market. In addition, nras and energy traders mostly agree that the eu has a nearly functional internal energy market and that acer is vitally important for the functioning of the internal market. [ABSTRACT FROM AUTHOR]

Thyroid cancer is the most common sort of endocrine-related cancer with more prevalent in women and elderly individuals which has quickly widespread expansion in worldwide over the recent decades. Common features of malignant thyroid cells are to have accelerated metabolism and increased glucose uptake to optimize their energy supply which provides a fundamental advantage for growth. In tumor cells the retaining of required energy charge for cell survival is imperative, indeed glucose transporters are enable of promoting of this task. According to this relation it has been reported the upregulation of glucose transporters in various types of cancers. Human studies indicated that poor survival can be occurred following the high levels of GLUT1 expression in tumors. GLUT-1 and GLUT3 are the glucose transporters which seems to be mainly engaged with the oncogenesis of thyroid cancer and their expression in malignant tissues is much more than in the normal one. They are promising targets for the advancement of anticancer strategies. The lack of oncosuppressors have dominant effect on the membrane expression of GLUT1 and glucose uptake. Overexpression of hypoxia inducible factors have been additionally connected with distant metastasis in thyroid cancers which mediates transcriptional regulation of glycolytic genes including GLUT1 and GLUT3. Though the physiological role of the thyroid gland is well illustrated, but the metabolic regulations in thyroid cancer remain evasive. In this study we discuss proliferation pathways of the key regulators and signaling molecules such as PI3K-Akt, HIF-1, MicroRNA, PTEN, AMPK, BRAF, c-Myc, TSH, Iodide and p53 which includes in the regulation of GLUTs in thyroid cancer cells. Incidence of deregulations in cellular energetics and metabolism are the most serious signs of cancers. In conclusion, understanding the mechanisms of glucose transportation in normal and pathologic thyroid tissues is critically important and could provide significant insights in science of diagnosis and treatment of thyroid disease. Video Abstract [ABSTRACT FROM AUTHOR]