Miracle-dz/UniFAR-FTUs huggingface dataset:
Mutational Analysis and Biochemical Characterization of the Burkholderia thailandensis DW503 Quorum-Sensing Network

ABSTRACT Numerous gram-negative bacteria communicate and regulate gene expression through a cell density-responsive mechanism termed quorum sensing (QS), which involves the synthesis and perception of diffusible N-acyl-homoserine lactones (AHL). In this study we genetically and physiologically characterized the Burkholderia thailandensis DW503 QS network. In silico analysis of the B. thailandensis genome revealed the presence of at least three AHL synthases (AHS) and five transcriptional regulators belonging to the LuxIR family of proteins. Mass spectrometry demonstrated that wild-type B. thailandensis synthesizes N-hexanoyl-homoserine lactone (C6-HSL), N-octanoyl-homoserine lactone (C8-HSL), and N-decanoyl-homoserine lactone (C10-HSL). Mutation of the btaI1 (luxI) AHS gene prevented accumulation of C8-HSL in culture supernatants, enhanced beta-hemolysis of sheep erythrocytes, increased lipase production, and altered colony morphology on swarming and twitching motility plates. Disruption of the btaI3 (luxI) AHS prevented biosynthesis of C6-HSL and increased lipase production and beta-hemolysis, whereas mutagenesis of the btaI2 (luxI) allele eliminated C10-HSL accumulation and reduced lipase production. Complementation of the btaI1 and btaI3 mutants fully restored the synthesis of C8-HSL and C6-HSL to parental levels. In contrast, mutagenesis of the btaR1, btaR3, btaR4, and btaR5 (luxR) transcriptional regulators had no effect on AHL accumulation, enhanced lipase production, and resulted in extensive beta-hemolysis on sheep blood agar plates. Furthermore, interruption of the btaI1, btaR1, and btaR3 genes altered colony morphology on twitching and swarming motility plates and induced pigmentation. Additionally, phenotypic microarray analysis indicated that QS in B. thailandensis both positively and negatively affects the metabolism of numerous substrates, including citric acid, formic acid, glucose 6-phosphate, capric acid, γ-hydroxybutyric acid, and d-arabinose. These results demonstrate that mutagenesis of the B. thailandensis QS system affects various cellular processes, including lipase production, swarming and twitching motility, beta-hemolysis of sheep erythrocytes, and carbon metabolism and/or transport.
A systematic review of informal caregivers' needs in providing home-based end-of-life care to people with cancer.

AIMS This paper presents the results of a systematic review examining the practical information needs of informal caregivers providing home-based palliative and end-of-life care to people with advanced cancer. BACKGROUND Modern hospice care has led to increases in home-based palliative care services, with informal caregivers assuming responsibility for the majority of care. In response, health policy emphasises the provision of palliative care services in which both the patient and carer receive adequate support throughout illness and death. While the emotional needs of carers have been extensively researched, their practical needs with respect to the provision of physical care are yet to receive systematic attention. DESIGN Systematic review. METHODS Eligible articles were identified via electronic searches of research and evidence-based databases, hand-searching of academic journals and searches of non-academic grey literature websites. Quality of research was assessed via accepted guidelines for reviewing non-randomised, observational and qualitative literature. Data were synthesised by comparing and contrasting the findings to identify prominent themes. RESULTS Research consistently highlights this lack of practical support, often related to inadequate information exchange. These deficits typically manifest in relatives adopting a 'trial and error' approach to palliative care. Informal carers request a greater quantity of practically-focussed information, improvements in quality and increased methods of dissemination. CONCLUSION Synthesis of the literature suggests that home-based palliative care services have been insufficiently focussed on assisting informal caregivers acquire practical nursing skills. RELEVANCE TO CLINICAL PRACTICE Enhanced access to professional advice represents a potentially effective method of increasing carers' confidence in their ability to undertake practical aspects of home-based care. Evidence suggests that nurses and other health providers may better assist home-based carers by providing the information and skills-training necessary to facilitate this. This may necessitate the involvement of carers in the design and testing of new educational interventions.
Borderline personality disorder in adolescence : An expert research review with implications for clinical practice

Borderline personality disorder (BPD) has onset in adolescence but is typically first diagnosed in young adulthood. This paper provides a narrative review of the current evidence on diagnosis, comorbidity, phenomenology and treatment of BPD in adolescence. Instruments available for diagnosis are reviewed and their strengths and limitations discussed. Having confirmed the robustness of the diagnosis and the potential for its reliable clinical assessment, we then explore current understandings of the mechanisms of the disorder and focus on neurobiological underpinnings and research on psychological mechanisms. Findings are accumulating to suggest that adolescent BPD has an underpinning biology that is similar in some ways to adult BPD but differs in some critical features. Evidence for interventions focuses on psychological therapies. Several encouraging research studies suggest that early effective treatment is possible. Treatment development has just begun, and while adolescent-specific interventions are still in the process of evolution, most existing therapies represent adaptations of adult models to this developmental phase. There is also a significant opportunity for prevention, albeit there are few data to date to support such initiatives. This review emphasises that there can be no justification for failing to make an early diagnosis of this enduring and pervasive problem.
Nef stimulates human immunodeficiency virus type 1 proviral DNA synthesis

The Nef protein of human immunodeficiency virus type 1 (HIV-1) stimulates viral infectivity. The mechanism of this phenotype was investigated. Viruses containing disrupted nef genes were 4 to 40 times less infectious than wild-type HIV-1 in a single-round infection. The Nef-mediated stimulation HIV-1 infectivity was dependent on the association of Nef with the plasma membrane and could be observed when Nef was provided in trans in the virus producer but not target cells. The impaired infectiousness of nef-defective (delta Nef) virions was observed whether or not CD4 was present in either of these cells. Furthermore, it was independent of the mode of viral entry, since it was not rescued by pseudotyping Env- HIV-1 virions with the amphotropic murine leukemia virus envelope glycoproteins. As predicted from this result, wild-type and delta Nef virions entered cells with equal efficiencies. However, despite their normal content in viral genomic RNA and reverse transcriptase activity, delta Nef viruses were limited in their ability to perform reverse transcription once internalized in several cell types, including peripheral blood lymphocytes. Since Nef does not appear to be abundant in virions, these results suggest that Nef acts in producer cells to allow the generation of particles fully competent for completing steps that follow entry, leading to efficient reverse transcription of the HIV-1 genome. Using a trans complementation assay, we found that Nef proteins from a number of primary HIV-1 isolates as well as, to a milder degree, those from HIV-2ST and SIVMAC239 could enhance the infectivity of delta Nef HIV-1. This indicates that the Nef-mediated stimulation of proviral DNA synthesis is highly conserved and likely plays an important role in vivo.
99mTc‐Tetrofosmin for Functional Imaging of P‐glycoprotein Modulation In Vivo

Tetrofosmin is a widely available and conveniently prepared tracer that has been shown to be a transport substrate for Pgp and MRP in vitro and in vivo. Its properties are similar but not identical to those of sestamibi. The available data suggest that clinical studies involving imaging of MDR function and in vivo modulation of MDR function could be performed with tetrofosmin or sestamibi, but the two should probably not be used interchangeably.
Forecasting volatility data based on Wavelet transforms and ARIMA model

This article suggests a novel technique for forecasting the volatility data based on Wavelet transforms and ARIMA model. The volatility data are decomposed via Wavelet transforms. Then, the future observations of this series are forecasted using a suitable and best fitted ARIMA model. Daily prices from Amman Stocks Market (Jordan) from 1993 until 2009 are used in this study.
Ultrastructure of ubiquitin‐positive, TDP‐43‐negative neuronal inclusions in cerebral cortex of C9ORF72‐linked frontotemporal lobar degeneration/amyotrophic lateral sclerosis

In a recent issue of Neuropathology, Troakes and colleagues described four cases of clinically pure motor neuron disease/amyotrophic lateral sclerosis (MND/ALS) phenotype (without dementia) but with distinctive cortical and cerebellar pathology that were different from other proteinopathies of TDP-43 (transactive response DNSbinding protein of 43 kD). Neuronal inclusions (NCIs) in cerebral cortex, hippocampus and cerebellum were immuno-positive for p62, a ubiquitin-binding protein, but negative for TDP-43. The inclusions were also positive for ubiquitin, albeit weaker than p62. Genetic analysis showed that all cases contained the C9ORF72 repeat expansion, the recently reported cause of chromosome 9-linked ALS and frontotemporal dementia (c9FTD/ALS). Tissues from one of the cases were processed for routine electron microscopy (EM). The authors described the ultrastructure of NCI as “ill-defined round bodies of granular and membranous material with few mitochondria mixed with a large amount of what appeared to be lipofuscin. Occasional filaments and microtubules were also seen”. During our study of c9FTD/ALS cases from our brain bank, we characterized ultrastructural features of NCIs and found them to be different from those reported by Troakes et al. Since routine EM may not distinguish TDP-43-positive from TDP-43-negative NCIs, we performed serial section, immunogold EM labeling with antibodies to ubiquitin and to TDP-43 on tissues from the entorhinal cortex of a c9FTD/ALS case. The tissue was processed for embedding in LR White resin (medium grade, Electron Microscopy Sciences, Hatfield, PA, USA) as previously described. Thin sections collected on Formvar-coated nickle grids were: (i) heated over citrate buffer, pH 6, in a 100°C oven for 10 min before incubation with a rabbit polyclonal antibody to TDP-43 (ProteinTech Group, Chicago. IL, USA); or (ii) incubated with a rabbit polyclonal antibody to ubiquitin without antigen retrieval pretreatment, followed by gold-conjugated goat anti-rabbit IgG (Jackson ImmunoResearch, West Grove, PA, USA). Images were taken with a Philips 208S electron microscope fitted with a Gatan charged-coupled device camera (Orius 831), and processed with Adobe Photoshop software. Neuronal inclusions were discernible at low magnification as distinct structures, usually one NCI per cell. None of the NCIs were membrane-bound. In the same section we were able to find NCIs that were immunopositive for TDP-43 (Fig. 1) as well as those that were
Elimination of Low-Frequency Ripples and Regulation of Neutral-Point Voltage in Stacked Multicell Converters

This paper introduces a modulation method for the stacked multicell converters (SMCs). The proposed method is implemented using phase-disposition pulse width modulation and is capable of balancing and regulating the voltages of all the capacitors in the topology, i.e., the flying capacitors and the dc-link capacitors. The proposed method is also able to eliminate the lowfrequency voltage ripples that may appear in the neutral point (NP) of SMCs. In SMCs with two stacks, the NP voltage level can be generated by direct connection of the output to the dc-link NP, but also using two extra states available. This redundancy is used to regulate the NP voltage. Furthermore, since the proposed method can eliminate the low-frequency voltage ripples in the capacitors, the capacitances of all the capacitors of the SMCs can be reduced, while maintaining high quality of the output voltages and currents. This enables the use of film capacitors. Simulation and experimental results are presented from a three-phase five-level 2 × 2 SMC to verify the effectiveness of the proposed method.
Randomized phase III trial of maintenance bevacizumab with or without pemetrexed after first-line induction with bevacizumab, cisplatin, and pemetrexed in advanced nonsquamous non-small-cell lung cancer: AVAPERL (MO22089).

PURPOSE Maintenance therapy is associated with improved survival in patients with non-small-cell lung cancer (NSCLC), but few studies have compared active agents in this setting. AVAPERL evaluated the safety and efficacy of bevacizumab with or without pemetrexed as continuation maintenance treatment. PATIENTS AND METHODS Patients with advanced nonsquamous NSCLC received first-line bevacizumab 7.5 mg/kg, cisplatin 75 mg/m(2), and pemetrexed 500 mg/m(2) once every 3 weeks for four cycles. Those achieving response or stable disease were randomly assigned at a ratio of 1:1 to maintenance bevacizumab 7.5 mg/kg or bevacizumab 7.5 mg/kg plus pemetrexed 500 mg/m(2) once every 3 weeks until disease progression or unacceptable toxicity. The primary end point was progression-free survival (PFS) after random assignment. RESULTS In total, 376 patients received induction treatment, 71.9% achieved disease control, and 67.3% were randomly assigned to maintenance therapy, with 125 and 128 receiving single-agent bevacizumab and bevacizumab plus pemetrexed treatment, respectively. At a median follow-up of 8.1 months, PFS from random assignment was significantly improved in the bevacizumab plus pemetrexed arm (median, 3.7 v 7.4 months; hazard ratio, 0.48; 95% CI, 0.35 to 0.66; P < .001) per a stratified model. The PFS benefit extended across age, performance status, smoking history, and induction response (stable disease v partial response) subgroups. Any grade, grade ≥ 3, and serious adverse events occurred more often with bevacizumab plus pemetrexed maintenance. No new safety signals were observed. CONCLUSION In an unselected population of patients with nonsquamous NSCLC who had achieved disease control with platinum-based chemotherapy plus bevacizumab, bevacizumab plus pemetrexed maintenance was associated with a significant PFS benefit compared with bevacizumab alone. The combination was well tolerated.
A study on modeling nitrogen dioxide concentrations using land-use regression and conventionally used exposure assessment methods

The land-use regression (LUR) approach to estimate the levels of ambient air pollutants is becoming popular due to its high validity in predicting small-area variations. However, only a few studies have been conducted in Asian countries, and much less research has been conducted on comparing the performances and applied estimates of different exposure assessments including LUR. The main objectives of the current study were to conduct nitrogen dioxide (NO2) exposure assessment with four methods including LUR in the Republic of Korea, to compare the model performances, and to estimate the empirical NO2 exposures of a cohort. The study population was defined as the year 2010 participants of a government-supported cohort established for bio-monitoring in Ulsan, Republic of Korea. The annual ambient NO2 exposures of the 969 study participants were estimated with LUR, nearest station, inverse distance weighting, and ordinary kriging. Modeling was based on the annual NO2 average, traffic-related data, land-use data, and altitude of the 13 regularly monitored stations. The final LUR model indicated that area of transportation, distance to residential area, and area of wetland were important predictors of NO2. The LUR model explained 85.8% of the variation observed in the 13 monitoring stations of the year 2009. The LUR model outperformed the others based on leave-one out cross-validation comparing the correlations and root-mean square error. All NO2 estimates ranged from 11.3–18.0 ppb, with that of LUR having the widest range. The NO2 exposure levels of the residents differed by demographics. However, the average was below the national annual guidelines of the Republic of Korea (30 ppb). The LUR models showed high performances in an industrial city in the Republic of Korea, despite the small sample size and limited data. Our findings suggest that the LUR method may be useful in similar settings in Asian countries where the target region is small and availability of data is low.
Estimación del spread de tasas de corto y largo plazo: Un indicador de alerta temprana

The relation between short and long term rates spread and economic growth has been widely argued on the international literature. Evidence from developed countries shows that the term structure of interest rates, frequently, contains relevant information concerning the economic growth dynamics. In many cases, the recession periods on the economy has been preceded by negative spreads, that means the short term interest rates exceed the long term ones (an interest rate reversion). Lately in Chile, it has been observed a greater convergence between short term interest rates (measured by the monetary policy real interest rate) and long term interest rates (measured by the 15 years mortgage rate). In fact, if we consider that the interest rate spread could be a leading indicator for future economic activity it would be interesting to know the spread evolution. The objective of this paper is to measure statistically the persistence of the present spread and estimate its long term evolution. The main finding is that the spread level is likely to stay on a low spread and volatility regime, but the statistic evidence does not show that the economy presents an interest rate reversion on the long run. Then, the most likely scenario is that on the long run the economy presents a growth rate similar to its potential.
Structure of D -lactate dehydrogenase from Aquifex aeolicus complexed with NAD + and lactic acid (or pyruvate)

Molecular Biophysics Group, School of Biological Sciences, University of Liverpool, Crown Street, Liverpool L69 7ZB, England, STFC Daresbury Laboratory, Warrington, Cheshire WA4 4AD, England, Systems and Structural Biology Center, Yokohama Institute, RIKEN, 1-7-22 Suehiro, Tsurumi, Yokohama 230-0045, Japan, RIKEN SPring-8 Center, Harima Institute, 1-1-1 Kouto, Sayo, Hyogo 679-5148, Japan, Department of Biological Sciences, Graduate School of Science, Osaka University, 1-1 Machikaneyama, Toyonaka, Osaka 560-0043, Japan, and Department of Biophysics and Biochemistry, Graduate School of Science, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan
Next-Generation Beneficial Microbes: The Case of Akkermansia muciniphila

Metabolic disorders associated with obesity and cardiometabolic disorders are worldwide epidemic. Among the different environmental factors, the gut microbiota is now considered as a key player interfering with energy metabolism and host susceptibility to several non-communicable diseases. Among the next-generation beneficial microbes that have been identified, Akkermansia muciniphila is a promising candidate. Indeed, A. muciniphila is inversely associated with obesity, diabetes, cardiometabolic diseases and low-grade inflammation. Besides the numerous correlations observed, a large body of evidence has demonstrated the causal beneficial impact of this bacterium in a variety of preclinical models. Translating these exciting observations to human would be the next logic step and it now appears that several obstacles that would prevent the use of A. muciniphila administration in humans have been overcome. Moreover, several lines of evidence indicate that pasteurization of A. muciniphila not only increases its stability but more importantly increases its efficacy. This strongly positions A. muciniphila in the forefront of next-generation candidates for developing novel food or pharma supplements with beneficial effects. Finally, a specific protein present on the outer membrane of A. muciniphila, termed Amuc_1100, could be strong candidate for future drug development. In conclusion, as plants and its related knowledge, known as pharmacognosy, have been the source for designing drugs over the last century, we propose that microbes and microbiomegnosy, or knowledge of our gut microbiome, can become a novel source of future therapies.
A general modeling framework for describing spatially structured population dynamics

Abstract Variation in movement across time and space fundamentally shapes the abundance and distribution of populations. Although a variety of approaches model structured population dynamics, they are limited to specific types of spatially structured populations and lack a unifying framework. Here, we propose a unified network‐based framework sufficiently novel in its flexibility to capture a wide variety of spatiotemporal processes including metapopulations and a range of migratory patterns. It can accommodate different kinds of age structures, forms of population growth, dispersal, nomadism and migration, and alternative life‐history strategies. Our objective was to link three general elements common to all spatially structured populations (space, time and movement) under a single mathematical framework. To do this, we adopt a network modeling approach. The spatial structure of a population is represented by a weighted and directed network. Each node and each edge has a set of attributes which vary through time. The dynamics of our network‐based population is modeled with discrete time steps. Using both theoretical and real‐world examples, we show how common elements recur across species with disparate movement strategies and how they can be combined under a unified mathematical framework. We illustrate how metapopulations, various migratory patterns, and nomadism can be represented with this modeling approach. We also apply our network‐based framework to four organisms spanning a wide range of life histories, movement patterns, and carrying capacities. General computer code to implement our framework is provided, which can be applied to almost any spatially structured population. This framework contributes to our theoretical understanding of population dynamics and has practical management applications, including understanding the impact of perturbations on population size, distribution, and movement patterns. By working within a common framework, there is less chance that comparative analyses are colored by model details rather than general principles.