Miracle-dz/UniFAR-FTUs huggingface dataset:
A Family of Negative Regulators Targets the Committed Step of de Novo Fatty Acid Biosynthesis[OPEN]

A novel, interacting protein with acetyl-CoA carboxylase resembles a known subunit but functions as a dominant-negative regulator of this multienzyme complex. Acetyl-CoA carboxylase (ACCase) catalyzes the committed step of de novo fatty acid biosynthesis. In prokaryotes, green algae, and most plants, this enzyme is a heteromeric complex requiring four different subunits for activity. The plant complex is recalcitrant to conventional purification schemes and hence the structure and composition of the full assembly have been unclear. In vivo coimmunoprecipitation using subunit-specific antibodies identified a novel family of proteins in Arabidopsis thaliana annotated as biotin/lipoyl attachment domain containing (BADC) proteins. Results from yeast two-hybrid and coexpression in Escherichia coli confirmed that all three BADC isoforms interact with the two biotin carboxyl carrier protein (BCCP) isoforms of Arabidopsis ACCase. These proteins resemble BCCP subunits but are not biotinylated due to a mutated biotinylation motif. We demonstrate that BADC proteins significantly inhibit ACCase activity in both E. coli and Arabidopsis. Targeted gene silencing of BADC isoform 1 in Arabidopsis significantly increased seed oil content when normalized to either mass or individual seed. We conclude the BADC proteins are ancestral BCCPs that gained a new function as negative regulators of ACCase after initial loss of the biotinylation motif. A functional model is proposed.
The compact FBG-based humidity sensor setup

This paper presents a concept of novel intensity-modulated humidity optical sensor with cascaded and spectrally overlapped fiber Bragg gratings (FBGs). Basically, the sensor consists of broadband light source, circulator, FBG sensitive to humidity and temperature (polymer-coated FBG), standard FBG (compensation of temperature influence) and optical power meter. In this setup the light is propagating through circulator to these FBGs and the whole reflected light is then directed to detector. Both standard FBG and polymer-coated FBG are assumed to be placed serially. This approach provides that the value of detected optical power is a complex function of the reflections from FBGs. Although polymer-coated FBG is sensitive not only to humidity, but also to temperature, the proposed sensor is an attempt of overcoming this problem. Overlapping spectra of FBGs and similar temperature sensitivities of FBGs imply that the sensor is able to response to change of relative humidity (RH), simultaneously having minimized temperature sensitivity. The sensor setup was verified experimentally in a temperature range from 25°C to 50°C and relative humidity from 30%RH to 70%RH. Instead of usage of high cost and complex devices, such as optical spectrum analyzer, the concept of alternative intensity-modulated FBG-based optical sensor for humidity measurement is clearly presented.
Efficacy and safety of paricalcitol therapy for chronic kidney disease: a meta-analysis.

BACKGROUND AND OBJECTIVES Observational data indicate that newer vitamin D compounds such as paricalcitol can suppress serum intact parathyroid hormone (iPTH) and reduce proteinuria in patients with CKD. To systematically evaluate the efficacy and safety of paricalcitol for CKD, we conducted a meta-analysis of the published randomized controlled trials (RCTs). DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS MEDLINE, Embase, the Cochrane Library, and article reference lists were searched for RCTs that compared paricalcitol with placebo in the treatment of patients with stage 2-5 CKD. The quality of the studies was evaluated using the Jadad method. The results are summarized as risk ratios (RRs) for dichotomous outcomes or mean differences for continuous outcomes. RESULTS Nine studies (832 patients) were included. Compared with placebo, paricalcitol suppressed serum iPTH (RR, 6.37; 95% confidence interval [95% CI], 4.64-8.74; P<0.001) and reduced proteinuria (RR, 1.68; 95% CI, 1.25-2.25; P<0.001). Compared with the control group, the RR for hypercalcemia associated with paricalcitol use was 2.25 (95% CI, 0.81-6.26; P=0.12). Patients receiving paricalcitol therapy did not have an increased risk of endocrine system and cardiovascular system adverse effects (RR, 1.07; 95% CI, 0.84-1.36; P=0.58). CONCLUSIONS We conﬁrm that paricalcitol suppresses iPTH and lowers proteinuria in patients with stage 2-5 CKD without an increased risk of adverse events. A trend toward increased hypercalcemia did not reach statistical signiﬁcance, but may be clinically relevant. A randomized trial is needed to determine if paricalcitol affects the development of ESRD or mortality.
Long-Chain Acyl-Homoserine Lactone Quorum-Sensing Regulation of Rhodobacter capsulatus Gene Transfer Agent Production

ABSTRACT Many proteobacteria use acyl-homoserine lactones as quorum-sensing signals. Traditionally, biological detection systems have been used to identify bacteria that produce acyl-homoserine lactones, although the specificities of these detection systems can limit discovery. We used a sensitive approach that did not require a bioassay to detect production of long-acyl-chain homoserine lactone production by Rhodobacter capsulatus and Paracoccus denitrificans. These long-chain acyl-homoserine lactones are not readily detected by standard bioassays. The most abundant acyl-homoserine lactone was N-hexadecanoyl-homoserine lactone. The long-chain acyl-homoserine lactones were concentrated in cells but were also found in the culture fluid. An R. capsulatus gene responsible for long-chain acyl-homoserine lactone synthesis was identified. A mutation in this gene, which we named gtaI, resulted in decreased production of the R. capsulatus gene transfer agent, and gene transfer agent production was restored by exogenous addition of N-hexadecanoyl-homoserine lactone. Thus, long-chain acyl-homoserine lactones serve as quorum-sensing signals to enhance genetic exchange in R. capsulatus.
Characterization of parathyroid hormone/receptor interactions: structure of the first extracellular loop.

The structural features of the first extracellular loop (ECL1) of the parathyroid hormone receptor (PTH1R) in the presence of dodecylphosphocholine micelles have been determined using high-resolution NMR techniques. The structure of the receptor fragment, PTH1R(241-285), includes three alpha-helices for residues 241-244, 256-264, and 275-284. The first and third correspond to the end and the beginning of transmembrane helices 2 and 3, respectively. Centrally located in the second helix is L(261), found to cross-link to Lys(27) of parathyroid hormone, PTH(1-34) [Greenberg, Z. , Bisello, A. , Mierke, D. F. , Rosenblatt, M. , and Chorev, M. (2000) Biochemistry 39, 8142-8152]. On the basis of nitroxide radical-induced relaxation studies, the central helix is found to associate with the surface of the membrane mimetic. These data, in conjunction with previous results indicating a preference of PTH for the lipid surface, suggest a membrane-associated pathway for the initial recognition and binding of PTH to its G-protein-coupled receptor. Using the structural features of ECL1 as determined here, along with the structure of the PTH(1-34), the intermolecular interactions consistent with the contact point between L(261)(receptor)-Lys(27)(ligand) are identified.
Previous antimalarial therapy in patients diagnosed with lupus nephritis: Influence on outcomes and survival

The aim of this study was to analyze the effect of exposure to antimalarial drugs at diagnosis of lupus nephritis on the outcome of the disease, especially renal failure, comorbid processes, and survival. We analyzed a cohort of 206 consecutive patients with biopsy-proven lupus nephritis. Renal biopsies were categorized according to the classification proposed by the ISN/RPS in 2003. Exposure to antimalarial drugs (chloroquine and hydroxychloroquine) was defined as the use of these drugs before the diagnosis of lupus nephritis independent of dose and duration. Fifty-six (27%) patients had received antimalarials before the diagnosis of lupus nephritis. During the follow-up, these patients had a lower frequency of creatinine values >4 mg/dL (2% vs 11%, P = 0.029) and end-stage renal failure (2% vs 11%, P = 0.044) in comparison with those never treated with antimalarials. Patients exposed to antimalarials also had a lower frequency of hypertension (32% vs 50%, P = 0.027), infections (11% vs 29%, P = 0.006), and thrombotic events (5% vs 17%, P = 0.039). Twenty patients (10%) died during the study period. Patients exposed to antimalarials had a lower mortality rate at the end of the follow-up (2% vs 13% for those not exposed to antimalarials, P = 0.029). Multivariate analysis identified thrombosis and infections as statistically significant independent variables. Kaplan–Meier plots showed a lower rate of end-stage renal failure (log rank = 0.04) in patients exposed to antimalarials. In conclusion, exposure to antimalarials before the diagnosis of lupus nephritis was negatively associated with the development of renal failure, hypertension, thrombosis and infection, and with a better survival rate at the end of the follow-up. This, together with other published data, suggests that antimalarials should be considered a mandatory therapeutic option in all patients diagnosed with systemic lupus erythematosus.
Chronic fishing disturbance has changed shelf sea benthic community structure

Summary 1. Bottom fishing using towed nets and dredges is one of the most widespread sources of physical disturbance to the continental shelf seas throughout the world. Previous studies suggest that degradation and ecosystem changes have occurred in intensively fished areas. Nevertheless, to date it has been difficult to attribute habitat and benthic community changes to fishing effort at a spatial scale that is truly representative of commercial fishing activities. 2. In this study we present convincing evidence that chronic bottom-fishing disturbance has caused significant and widespread changes in the structure of two distinct soft-sediment benthic assemblages and habitats. 3. Our study compared the benthic fauna found in areas that have been exposed to either high or low levels of bottom-fishing disturbance over the past 10 years. We were able to validate the fishing effort data in some areas using scars in the shells of a long-lived bivalve mollusc (Glycymeris glycymeris) which result from fishing disturbance. Shell scars occurred most frequently in bivalves collected from the area of highest fishing effort. 4. Multivariate analyses and the response of abundance/biomass curves indicated that chronic fishing has caused a shift from communities dominated by relatively sessile, emergent, high biomass species to communities dominated by infaunal, smaller-bodied fauna. Removal of emergent fauna has thus degraded the topographic complexity of seabed habitats in areas of high fishing effort. The communities within these areas currently may be in an alternative stable state.
Multi-nucleate retinal pigment epithelium cells of the human macula exhibit a characteristic and highly specific distribution

Abstract Background: The human retinal pigment epithelium (RPE) is reportedly 3% bi-nucleated. The importance to human vision of multi-nucleated (MN)-RPE cells could be clarified with more data about their distribution in central retina. Methods: Nineteen human RPE-flatmounts (9 ≤ 51 years, 10 > 80 years) were imaged at 12 locations: 3 eccentricities (fovea, perifovea, near periphery) in 4 quadrants (superior, inferior, temporal, nasal). Image stacks of lipofuscin-attributable autofluorescence and phalloidin labeled F-actin cytoskeleton were obtained using a confocal fluorescence microscope. Nuclei were devoid of autofluorescence and were marked using morphometric software. Cell areas were approximated by Voronoi regions. Mean number of nuclei per cell among eccentricity/quadrant groups and by age were compared using Poisson and binominal regression models. Results: A total of 11,403 RPE cells at 200 locations were analyzed: 94.66% mono-, 5.31% bi-, 0.02% tri-nucleate, and 0.01% with 5 nuclei. Age had no effect on number of nuclei. There were significant regional differences: highest frequencies of MN-cells were found at the perifovea (9.9%) and near periphery (6.8%). The fovea lacked MN-cells almost entirely. The nasal quadrant had significantly more MN-cells compared to other quadrants, at all eccentricities. Conclusion: This study demonstrates MN-RPE cells in human macula. MN-cells may arise due to endoreplication, cell fusion, or incomplete cell division. The topography of MN-RPE cells follows the topography of photoreceptors; with near-absence at the fovea (cones only) and high frequency at perifovea (highest rod density). This distribution might reflect specific requirements of retinal metabolism or other mechanisms addressable in further studies.
A Genomic Profile of the Immune Response to Stroke With Implications for Stroke Recovery

Objectives: The objectives of this study were to determine the change in gene expression between two time points following stroke and to identify biomarkers of stroke recovery through gene expression profiling and pathway analysis. Methods: Peripheral blood was collected from 34 ischemic stroke patients (confirmed by magnetic resonance imaging) ≥18 years of age, within 24 hr of symptom onset and 24–48 hr later, and from healthy controls. The Modified Rankin Scale (MRS) was used to determine 30-day recovery. Total RNA was extracted from whole blood in Paxgene RNA tubes, amplified, and hybridized to Illumina HumanRef-8v2 bead chips. Gene expression was compared in a univariate manner between stroke patients at both time points and good versus bad outcome using t-test in GeneSpring. Inflation of Type 1 error was corrected by false discovery rate (FDR), and Ingenuity Systems Pathway analysis (IPA) was performed. A secondary validation cohort was recruited from a local hospital. Results: Three genes were significantly downregulated over time (LY96, IL8, and SDPR; FDR corrected p < .05). This finding was confirmed in a validation cohort of stroke patients (n = 8). IPA revealed cytotoxic T-lymphocyte antigen 4 (CTLA4) signaling was the most significant pathway present in the peripheral whole blood of stroke patients 24–48 hr after onset. When controlling for age and National Institutes of Health Stroke Scale score, high baseline expression of TLR2 and TLR4 significantly predicted worse scores on the MRS. Conclusion: CTLA4 signaling is a novel pathway for the study of stroke-induced immune suppression. Markers of immune dysfunction early after stroke may prove useful for identifying patients with increased risk of poor recovery.
Interleukin 4 prevents the induction of tissue factor mRNA in human monocytes in response to LPS or PMA stimulation

Summary. Increased expression of tissue factor (TF) procoagulant activity by blood monocytes and tissue macrophages is implicated in a number of thrombotic disorders, as well as in fibrin deposition associated with inflammatory lesions and immunological diseases. We found that interleukin 4 (IL‐4), a T lymphocyte‐derived cytokine known to regulate a number of monocyte functions, inhibited the production of TF by monocytes in response to endotoxin and phorbol myristate acetate (PMA) in vitro. IL‐4 had a concentration‐dependent inhibitory effect on functional TF procoagulant activity (PCA) and reduced the binding of an anti‐TF antibody, as assessed by flow cytometry analysis. Moreover, IL‐4 reduced LPS‐ and PMA‐induced TF mRNA levels. TF mRNA stability was not modified by IL‐4 after the arrest of transcription by actinomycin D. We thus conclude that mRNA suppression is mediated by an effect occurring at the transcriptional level. Our results also show that the suppressive effect of IL‐4 is independent of an increase in the intracellular concentration of cyclic AMP, another established inhibitor of TF production. Locally produced IL‐4 might thus contribute to limiting the consequences of monocyte activation.
A prototypic platelet septin and its participation in secretion

Studies are presented characterizing platelet CDCrel-1, a protein expressed to high levels by megakaryocytes and belonging to a family of conserved proteins, termed septin. Septin filaments originally were identified in yeast as essential for budding but have become increasingly associated with processes in higher eukaryotic cells involving active membrane movement such as cytokinesis and vesicle trafficking. Direct proof of an in vivo function for septins in higher eukaryotes is limited to the characterization of the Drosophila septin, termed PNUT. We present studies identifying platelet CDCrel-1 as a protein kinase substrate in the presence of known platelet agonists. The immunopurification of CDCrel-1 revealed it to be part of a macromolecular complex containing a protein involved in platelet secretion, syntaxin 4. Moreover, CDCrel-1 was localized in situ to areas surrounding platelet-storage granules. The relevance of CDCrel-1 to normal platelet function was established with the characterization of platelets from a CDCrel-1Null mouse. As compared with platelets from wild-type littermates, CDCrel-1Null platelets aggregate and release stored [14C]serotonin in the presence of subthreshold levels of collagen. These results provide new insights into the mechanisms regulating platelet secretion and identify platelet septins as a protein family contributing to membrane trafficking within the megakaryocyte and platelet.
The Impact of Obesity on the Incidence and Treatment of Gynecologic Cancers: A Review

Sixty-five percent of the adult population in the United States is overweight and 30% of the population is obese. There is mounting evidence that obesity is a risk factor for gynecologic cancers and may also adversely impact survival. The objectives of this review were to systematically evaluate and discuss the impact of overweight and obesity on endometrial, ovarian, and cervical cancer incidence and to review the data on the impact of obesity on treatment of these same gynecologic cancers. A PUBMED literature search was performed to identify articles in the English language that focused on the impact of obesity on cancer incidence and treatment. References of identified articles were also used to find additional related articles. Obesity profoundly increases the incidence of endometrial cancer, predominantly through the effects of unopposed estrogen. Although the data are less compelling in ovarian and cervical cancer, obesity may modestly increase the incidence of premenopausal ovarian cancer and might potentially increase cervical cancer incidence, perhaps as a result of the impact on glandular cancers or decreased screening compliance. Obese women with cancer have decreased survival; this may be disease-specific, the result of comorbid illnesses, or response to treatment. Obese women have increased surgical complications, may also have increased radiation complications, and there is no current consensus regarding appropriate chemotherapy dosing in the obese patient. Obesity is a serious health problem with significant effects on the incidence and treatment of the gynecologic malignancies. Target Audience: Obstetricians & Gynecologists, Family Physicians. Learning Objectives: After completion of this article, the reader should be able to summarize the clear evidence that obesity is a risk factor for many cancers, including gynecologic malignancies; describe the role of unopposed estrogen in gynecologic cancers; and explain that obese women overall have a poorer survival rate when afflicted with cancer.
Intrusive memories in depression: an index of schema activation?

Synopsis A sample of 31 male and female depressed patients was interviewed to investigate spontaneous, intrusive memories of immediate and past life events. Previous findings that depressed patients experience high frequency intrusive memories were confirmed, as was an association between intrusive memories of childhood abuse and severity of depression. Patients reported intrusive memories for a variety of other events, particularly involving illness and death. Limited support was obtained for the hypotheses that the course of depression would be related to the activation of negative memories, and that immediate life events would trigger the activation of memories of similar events from the past.
A Co-Evolutionary Multi-Objective approach for a K-adaptive graph-based clustering algorithm

Clustering is a field of Data Mining that deals with the problem of extract knowledge from data blindly. Basically, clustering identifies similar data in a dataset and groups them in sets named clusters. The high number of clustering practical applications has made it a fertile research topic with several approaches. One recent method that is gaining popularity in the research community is Spectral Clustering (SC). It is a clustering method that builds a similarity graph and applies spectral analysis to preserve the data continuity in the cluster. This work presents a new algorithm inspired by SC algorithm, the Co-Evolutionary Multi-Objective Genetic Graph-based Clustering (CEMOG) algorithm, which is based on the Multi-Objective Genetic Graph-based Clustering (MOGGC) algorithm and extends it by introducing an adaptative number of clusters. CEMOG takes an island-model approach where each island keeps a population of candidate solutions for ki clusters. Individuals in the islands can migrate to encourage genetic diversity and the propagation of individuals around promising search regions. This new approach shows its competitive performance, compared to several classical clustering algorithms (EM, SC and K-means), through a set of experiments involving synthetic and real datasets.
Multi-UAV collision avoidance with separation assurance under uncertainties

This paper presents a collision avoidance method for multiple UAVs and other non-cooperative aircraft based on velocity planning and taking into account the trajectory prediction under uncertainties. The proposed method finds a safe trajectory from the predicted trajectory modifying the velocity profile of the different co-operative vehicles involved in the collision. A particle filter is used to predict the trajectories under uncertainties dealing with the influence of different sources of uncertainty such as the atmospheric conditions, the UAV model and the limitations of the sensors and control system on board the UAV.
Early life stress and telomere length: Investigating the connection and possible mechanisms

How can adverse experiences in early life, such as maltreatment, exert such powerful negative effects on health decades later? The answer may lie in changes to DNA. New research suggests that exposure to stress can accelerate the erosion of DNA segments called telomeres. Shorter telomere length correlates with chronological age and also disease morbidity and mortality. Thus, telomere erosion is a potential mechanism linking childhood stress to health problems later in life. However, an array of mechanistic, methodological, and basic biological questions must be addressed in order to translate telomere discoveries into clinical applications for monitoring health and predicting disease risk. This paper covers the current state of the science and lays out new research directions.