Miracle-dz/UniFAR-FTUs huggingface dataset:
CcpA and CodY Coordinate Acetate Metabolism in Streptococcus mutans

ABSTRACT In the dental caries pathogen Streptococcus mutans, phosphotransacetylase (Pta) and acetate kinase (Ack) convert pyruvate into acetate with the concomitant generation of ATP. The genes for this pathway are tightly regulated by multiple environmental and intracellular inputs, but the basis for differential expression of the genes for Pta and Ack in S. mutans had not been investigated. Here, we show that inactivation in S. mutans of ccpA or codY reduced the activity of the ackA promoter, whereas a ccpA mutant displayed elevated pta promoter activity. The interactions of CcpA with the promoter regions of both genes were observed using electrophoretic mobility shift and DNase protection assays. CodY bound to the ackA promoter region but only in the presence of branched-chain amino acids (BCAAs). DNase footprinting revealed that the upstream region of both genes contains two catabolite-responsive elements (cre1 and cre2) that can be bound by CcpA. Notably, the cre2 site of ackA overlaps with a CodY-binding site. The CcpA- and CodY-binding sites in the promoter region of both genes were further defined by site-directed mutagenesis. Some differences between the reported consensus CodY binding site and the region protected by S. mutans CodY were noted. Transcription of the pta and ackA genes in the ccpA mutant strain was markedly different at low pH relative to transcription at neutral pH. Thus, CcpA and CodY are direct regulators of transcription of ackA and pta in S. mutans that optimize acetate metabolism in response to carbohydrate, amino acid availability, and environmental pH. IMPORTANCE The human dental caries pathogen Streptococcus mutans is remarkably adept at coping with extended periods of carbohydrate limitation during fasting periods. The phosphotransacetylase-acetate kinase (Pta-Ack) pathway in S. mutans modulates carbohydrate flux and fine-tunes the ability of the organisms to cope with stressors that are commonly encountered in the oral cavity. Here, we show that CcpA controls transcription of the pta and ackA genes via direct interaction with the promoter regions of both genes and that branched-chain amino acids (BCAAs), particularly isoleucine, enhance the ability of CodY to bind to the promoter region of the ackA gene. A working model is proposed to explain how regulation of pta and ackA genes by these allosterically controlled regulatory proteins facilitates proper carbon flow and energy production, which are essential functions during infection and pathogenesis as carbohydrate and amino acid availability continually fluctuate.
On the determination of the volume fraction of Ni4Ti3 precipitates in binary Ni-rich NiTi shape memory alloys

Abstract The size distributions and volume fractions of Ni4Ti3 precipitates in Ni-rich Ni –Ti shape memory alloys affect their mechanical and functional properties. In the present work precipitate sizes and volume fractions were measured after various thermo-mechanical treatments using transmission electron microscopy (TEM) in combination with quantitative metallography. TEM tilting experiments revealed that the Ni4Ti3 particles have a disk-like shape with a disk diameter D and a disk thickness t. These two parameters together with the number density of particles per unit volume were determined after stress-free and stress-assisted aging at 400, 500 and 530 °C. Volume fraction results are presented after different thermo-mechanical treatments and our quantitative metallographic procedure is documented.
Alantolactone, a sesquiterpene lactone, inhibits breast cancer growth by antiangiogenic activity via blocking VEGFR2 signaling

Alantolactone (ALA), a sesquiterpene lactone isolated from several medicinal plants such as Inula helenium, has been identified to have attractive anticancer activity. However, its role in the inhibition of angiogenesis during tumor development remains unclear. In this study, we found ALA can inhibit the proliferation, motility, migration, and tube formation of human umbilical vein endothelial cells. ALA also restrained angiogenesis in chick embryo chorioallantoic membrane and delayed the growth of human MDA‐MB‐231 breast cancer xenograft in mice through angiogenesis inhibition. Furthermore, ALA suppressed the phosphorylation of vascular endothelial growth factor receptor 2 and its downstream protein kinase including PLCγ1, FAK, Src, and Akt in endothelial cells. Taken together, the antiangiogenic activity of ALA and its molecular mechanism are identified for the first time, indicating that ALA may be a potential drug candidate or lead compound for antiangiogenic cancer therapy.
States With Prescription Drug Monitoring Mandates Saw A Reduction In Opioids Prescribed To Medicaid Enrollees.

Prescription drug monitoring programs are promising tools to use in addressing the prescription opioid epidemic, yet prescribers' participation in these state-run programs remained low as of 2014. Statutory mandates for prescribers to register with their state's program, use it, or both are believed to be effective tools to realize the programs' full potential. Our analysis of aggregate Medicaid drug utilization data indicates that state mandates for prescriber registration or use adopted in 2011-14 were associated with a reduction of 9-10 percent in population-adjusted numbers of Schedule II opioid prescriptions received by Medicaid enrollees and amounts of Medicaid spending on these prescriptions. This effect was largely associated with mandates of registration, which were comprehensive in all adopting states, and not with mandates of use, which were largely limited in scope or strength before 2015. Our findings support the use of mandates of registration in prescription drug monitoring programs as an effective and relatively low-cost policy. Future research should further assess the value of strong mandates of use to ensure safer and more appropriate prescribing of opioids.
Magnetic-field sensor based on tapered all-solid waveguide-array fiber and magnetic fluids

A compact fiber-optic magnetic-field sensor based on tapered all-solid waveguide-array fiber (WAF) and magnetic fluid (MF) has been proposed and experimentally demonstrated. The transmission spectra of the fiber-optic magnetic field sensor have been measured and analyzed under different magnetic field intensities. Experimental results show that the acquired magnetic field sensitivity is 44.57 pm/Oe for a linear magnetic field intensity range from 50 Oe to 200 Oe. It also indicates that the magnetic field sensor based on tapered all-solid WAF and MF is helpful to reduce temperature cross-sensitivity for the measurement of magnetic field.
Immune response‐related genes associated to blocking midgut dengue virus infection in Aedes aegypti strains that differ in susceptibility

Aedes (Stegomyia) aegypti, the principal global vector of dengue viruses, has differences in its susceptibility to dengue virus infection. We compared the global expression of genes in the midguts of Colombian Ae. aegypti dengue‐susceptible (Cali‐S) and dengue‐refractory (Cali‐MIB) field derived strains after ingesting either a sugarmeal, a bloodmeal, or a bloodmeal containing dengue virus serotype 2 (DENV‐2). Microarray‐based transcriptome analysis among treatments indicated a total of 4725 transcripts with differential expression between the two strains. Eleven genes were selected from different functional groups based on their significant up or down expression levels as well as reports in the literature suggesting they are associated with dengue virus elimination. We measured mRNA abundance of these 11 genes at 0, 8, 24, and 36 h postinfection using quantitative real time PCR (qPCR) to confirm the microarray results and assess any temporal patterns. Four genes were selected (Gram‐negative binding protein—GNBP [AAEL009176], Niemann Pick Type‐C2—NPC2 [AAEL015136], Keratinocyte lectin [AAEL009842], and Cathepsin‐b [AAEL007585]) for knockdown experiments using RNA interference (RNAi) methodology to determine the phenotype (DENV‐2 susceptible or refractory). Silencing GNBP, Cathepsin‐b and Keratinocyte lectin reduced the percentage of mosquitoes with disseminated virus in the Cali‐S strain to 8%, 20%, and 12% respectively compared with 96% in the controls. Silencing of NPC2 increased the percentage of mosquitos with disseminated virus infections in Cali‐MIB to 66% compared with 35% in the controls. This study provides insight into genes that may contribute to the Cali‐S susceptible and Cali‐MIB refractory phenotypes in Ae. aegypti.
Optimization of Chitosan-Based Scaffolds Obtained via Cathodic Polarization

Cathodic polarization is a powerful technique largely used for the deposition of thin films on metallic substrates; it offers the distinctive advantage of an easy control over the composition, thickness, and morphology of the films by simply adjusting the process parameters such as the electrolyte bath composition, the applied potential (or current density), and the process duration. In this work, electrochemical deposition (ECD) was exploited to engender biopolymer blends composed by chitosan/collagen and chitosan/poly (ethylene oxide) and deposited at different weight ratios (5:1, 3:1) and compared to pristine material. Our findings demonstrate that ECD is an effective technique for the preparation of scaffolds made of chitosan blends in which morphology and mechanical properties can be optimized via scaffold composition.
Protocol for a single-centre, parallel-arm, randomised controlled superiority trial evaluating the effects of transcatheter arterial embolisation of abnormal knee neovasculature on pain, function and quality of life in people with knee osteoarthritis

Introduction Symptomatic knee osteoarthritis (OA) is common. Advanced knee OA is successfully treated with joint replacement surgery, but effectively managing mild to moderate knee OA can be difficult. Angiogenesis increases with OA and might contribute to pain and structural damage. Modifying angiogenesis is a potential treatment pathway for OA. The aim of the current study is to determine whether transcatheter arterial embolisation of abnormal neovasculature arising from the genicular arterial branches improves knee pain, physical function and quality of life in people with mild to moderate symptomatic knee OA. Methods and analysis The study is a single centre, parallel-arm, double-blinded (participant and assessor), randomised controlled superiority trial with 1:1 random block allocation. Eligible participants have mild to moderate symptomatic knee OA and will be randomly assigned to receive either embolisation of aberrant knee neovasculature of genicular arterial branches or a placebo intervention. Outcome measures will be collected prior to the intervention and again 1, 6 and 12 months postintervention. The primary outcome is change in knee pain between baseline and 12 month assessment as measured by the Knee Injury and Osteoarthritis Outcome Score (KOOS). Secondary outcomes include change in self-reported physical function (KOOS), self-reported quality of life (KOOS, EuroQol: EQ-5D-5L), self-reported knee joint stiffness (KOOS), self-reported global change, 6 min walk test performance, and 30 s chair-stand test performance. Intention-to-treat analysis will be performed including all participants as randomised. To detect a mean between group difference in change pain of 20% at the one year reassessment with a two-sided significance level of α=0.05 and power of 80% using a two-sample t-test, we require 29 participants per arm which allows for 20% of participants to drop out. Ethics and dissemination Barwon Health Human Research Ethics Committee, 30 May 2016, (ref:15/101). Study results will be disseminated via peer-reviewed publications and conference presentations. Trial registration number Universal trial number U1111-1183-8503, Australian New Zealand Clinical Trials Registry, ACTRN12616001184460, approved 29 August 2016.
Mechanical properties and failure mode of thermoplastic elastomers from natural rubber/poly(methyl methacrylate)/natural rubber‐g‐poly(methyl methacrylate) blends

The mechanical properties and fracture behavior of natural rubber/poly-(methyl methacrylate) blends were investigated as a function of composition, graft copolymer concentration, and mixing conditions. The mechanical properties and failure behavior vary with the blend ratio, graft copolymer concentration, and mixing conditions. Various two-phase models were used to fit the experimental mechanical properties. Mechanical properties such as stress–strain behavior, tensile strength, tensile modulus, tear strength, and Izod impact strength were evaluated as a function of compatibilizer concentration. The domain size of the dispersed phase decreases with graft copolymer concentration followed by a leveling off at higher concentration. The mechanical properties attain a maximum value at the leveling point, which is an indication of interfacial saturation and the attainment of maximum interfacial adhesion between the homopolymers. Tensile and tear fracture surfaces were examined by scanning electron microscopy. The detachment of the dispersed domains from the matrix is an indication of no adhesion between the two phases in the case of uncompatibilized blends. Microfibrils between the matrix and the dispersed phase indicate a sign of interfacial adhesion between the phases in the case of compatibilized blends. © 1997 John Wiley & Sons, Inc. J Appl Polm Sci 65:1245–1255, 1997
New Fundamental Defects in a-SO,

The atomic structure and spin properties of two previously undescribed amorphous silicon dioxide fundamental point defects have been characterized for the first time by ab initio quantum mechanical calculations. Both defects are electrically neutral trivalent silicon centers in the oxide. One of the defects, the X-center, is determined to have an O,Si=SiT atomic structure. The other defect, called the Ycenter, is found to have an OSi,=SiT structure. Calculated electronic and electrical properties of the new defect centers are consistent with the published characteristics of the oxide switching trap or border trap precursors.
Early childhood risk factors for constipation and soiling at school age: an observational cohort study

Objective Constipation and soiling are common in childhood. This study examines the comorbidity between childhood constipation and soiling and early childhood risk factors for these problems. Design The sample comprised 8435 participants from the Avon Longitudinal Study of Parents and Children with maternally reported measures of constipation (six time points between 4 and 10 years) and soiling (five time points between 4 and 9 years). We used latent class analysis to extract longitudinal patterns of constipation and soiling. We examined whether the latent classes are differentially associated with maternally reported risk factors in early childhood (stool consistency, breast feeding, socioeconomic background, gestation, birth weight, developmental level and age at initiation of toilet training) using multinomial logistic regression models. Results We extracted four latent classes: ‘normative’ (74.5%: very low probability of constipation or soiling), ‘constipation alone’ (13.2%), ‘soiling alone’ (7.5%) and ‘constipation with soiling’ (4.8%). Hard stools at 2½ years were associated with increased odds of constipation alone. Developmental delay at 18 months was associated soiling alone and constipation with soiling, but not constipation alone. We found limited evidence of associations with socioeconomic background and no evidence of associations with age at initiation of toilet training, breast feeding, gestational age or birth weight. Conclusion Constipation alone was the most prevalent pattern in this cohort. Treatment for hard stools in early childhood is needed to prevent chronic constipation at school age. Constipation with soiling was less common than soiling alone. Further research is needed into the causes of non-retentive soiling.
The Road to HLA Antibody Evaluation: Do Not Rely on MFI

Technological advances in HLA laboratory testing undoubtedly improved the sensitivity and specificity of HLA antibody assessment but not without introducing a set of challenges regarding data interpretation. In particular, the introduction of solid‐phase single‐antigen bead (SAB) antibody assessment brought the belief that mean fluorescence intensity (MFI) was a quantifiable value. As such, MFI levels heavily influenced HLA antibody reporting, monitoring, and clinical practice. However, given that SAB testing was neither intended for nor approved to be quantifiable, is the use of MFI in current clinical and laboratory practice valid? What, if anything, does this numerical value actually reveal about the pathogenic potential of the antibody? What are the pitfalls and caveats associated with reporting MFI? Herein, we travel the road to HLA antibody assessment and explore the reliability of MFI values to make clinical decisions.
Recent and Prospective Development of Functionally Graded Materials in Japan

The concept of functionally graded materials (FGMs), originally developed for the purpose of reducing thermal stress, has now greatly expanded and is being applied to the development of electrical, optical, magnetic, and biochemical materials. Here in Japan, several FGM research projects have been promoted with the support of the government and other organizations. Many societies concerned with material science now include special sessions or symposia on FGMs at their annual conferences to promote FGM research, and FGM research in Japan has been increasing year by year Many novel fabrication processes have been developed. and various new materials with unique properties have been prepared by introducing graded structures For example, achievement of successful control of electrical properties of perovskite-type (La 1-x Ca x ) MnO 3 has led to a new approach to the control electronic transport behavior by a graded structure, and the advanced optical filter characteristics of graded TiO 2 /SiO 2 multilayer film provide a new avenue not only for application of FGMs but also for understanding their mechanisms In this paper, some recent interesting findings on the design, process, and characteristics of FGMs are described. Future possibilities and trends in FGM research are also discussed.
Three-Dimensional Structure of the Ultraoligotrophic Marine Bacterium “Candidatus Pelagibacter ubique”

ABSTRACT SAR11 bacteria are small, heterotrophic, marine alphaproteobacteria found throughout the oceans. They thrive at the low nutrient concentrations typical of open ocean conditions, although the adaptations required for life under those conditions are not well understood. To illuminate this issue, we used cryo-electron tomography to study “Candidatus Pelagibacter ubique” strain HTCC1062, a member of the SAR11 clade. Our results revealed its cellular dimensions and details of its intracellular organization. Frozen-hydrated cells, which were preserved in a life-like state, had an average cell volume (enclosed by the outer membrane) of 0.037 ± 0.011 μm3. Strikingly, the periplasmic space occupied ∼20% to 50% of the total cell volume in log-phase cells and ∼50% to 70% in stationary-phase cells. The nucleoid occupied the convex side of the crescent-shaped cells and the ribosomes predominantly occupied the concave side, at a relatively high concentration of 10,000 to 12,000 ribosomes/μm3. Outer membrane pore complexes, likely composed of PilQ, were frequently observed in both log-phase and stationary-phase cells. Long filaments, most likely type IV pili, were found on dividing cells. The physical dimensions, intracellular organization, and morphological changes throughout the life cycle of “Ca. Pelagibacter ubique” provide structural insights into the functional adaptions of these oligotrophic ultramicrobacteria to their habitat. IMPORTANCE Bacterioplankton of the SAR11 clade (Pelagibacterales) are of interest because of their global biogeochemical significance and because they appear to have been molded by unusual evolutionary circumstances that favor simplicity and efficiency. They have adapted to an ecosystem in which nutrient concentrations are near the extreme limits at which transport systems can function adequately, and they have evolved streamlined genomes to execute only functions essential for life. However, little is known about the actual size limitations and cellular features of living oligotrophic ultramicrobacteria. In this study, we have used cryo-electron tomography to obtain accurate physical information about the cellular architecture of “Candidatus Pelagibacter ubique,” the first cultivated member of the SAR11 clade. These results provide foundational information for answering questions about the cell architecture and functions of these ultrasmall oligotrophic bacteria.
Care and support for older adults in The Netherlands living independently

The growth in the numbers of older adults needing long-term care has resulted in rising costs which have forced the Dutch government to change its long-term care system. Now, the local authorities have greater responsibility for supporting older adults and in prolonging independent living with increased support provided by the social network. However, it is unclear whether these older adults have such a network to rely upon. The objective of this study was to gain insight into the providers of formal and informal care to older adults, and to assess possible differences between older adults who are frail and those who are not. In addition, we investigated their care and support needs. We used data from a quantitative survey using a cross-sectional design in different regions of the Netherlands from July until September 2014 (n = 181). Frailty was measured using the Tilburg Frailty indicator. To analyse the data chi-square tests, crosstabs and odds ratios were used for dichotomous data and the Mann-Whitney U-Test for nominal data. The number of formal care providers involved was significantly higher (median = 2) for those deemed frail than for those not deemed frail (median = 1), U = 2,130, p < . 005. However, more than one-third of the respondents deemed frail did not get the care or support they needed (33.7%). There was a significant positive association between being frail and having an informal care provider (χ2 = 18.78, df = 1, p < .005). However, more than one-third of those deemed frail did not have an informal care provider (36.8%). One-third of older adults deemed to be frail did not have their needs sufficiently addressed by their care network. For a substantial part of this group of older adults, the informal network seems to be unable to support them sufficiently. Additional attention for their needs and wishes is required to implement the policy reforms successfully.
Telling plant species apart with DNA: from barcodes to genomes

Land plants underpin a multitude of ecosystem functions, support human livelihoods and represent a critically important component of terrestrial biodiversity—yet many tens of thousands of species await discovery, and plant identification remains a substantial challenge, especially where material is juvenile, fragmented or processed. In this opinion article, we tackle two main topics. Firstly, we provide a short summary of the strengths and limitations of plant DNA barcoding for addressing these issues. Secondly, we discuss options for enhancing current plant barcodes, focusing on increasing discriminatory power via either gene capture of nuclear markers or genome skimming. The former has the advantage of establishing a defined set of target loci maximizing efficiency of sequencing effort, data storage and analysis. The challenge is developing a probe set for large numbers of nuclear markers that works over sufficient phylogenetic breadth. Genome skimming has the advantage of using existing protocols and being backward compatible with existing barcodes; and the depth of sequence coverage can be increased as sequencing costs fall. Its non-targeted nature does, however, present a major informatics challenge for upscaling to large sample sets. This article is part of the themed issue ‘From DNA barcodes to biomes’.