Miracle-dz/UniFAR-FTUs huggingface dataset:
The DNA Binding Activity of the RIPE3b1 Transcription Factor of Insulin Appears to Be Influenced by Tyrosine Phosphorylation*

The RIPE3b1 DNA binding factor plays a critical role in pancreatic islet β cell-specific and glucose-regulated transcription of the insulin gene. Recently it was shown that RIPE3b1 binding activity in β cell nuclear extracts is reduced by treatment with either calf intestinal alkaline phosphatase (CIAP) or a brain-enriched phosphatase preparation (BPP) (Zhao, L., Cissell, M. A., Henderson, E., Colbran, R., and Stein, R. (2000)J. Biol. Chem. 275, 10532–10537). Evidence is presented here suggesting that a tyrosine phosphatase(s) influences the ability of RIPE3b1 to bind to the insulin C1 element in β cells. We found that RIPE3b1 binding was inhibited upon incubating β cell nuclear extracts at 30 °C. In contrast, PDX-1 and MLTF-1 transcription factor binding activity was unaffected under these conditions. The loss in RIPE3b1 binding activity was prevented by inhibitors of tyrosine phosphatases (sodium orthovanadate and sodium molybdate) but not by inhibitors of serine/threonine phosphatases (sodium fluoride, okadaic acid, and microcystin LR). CIAP- and BPP-catalyzed inhibition of RIPE3b1 binding was also blocked by these tyrosine phosphatase inhibitors. Collectively, the data suggested that removal of a tyrosine(s) within RIPE3b1 prevented activator binding to insulin C1 control element sequences. The presence of a key phosphorylated tyrosine(s) within this transcription factor was further supported by the ability of the 4G10 anti-phosphotyrosine monoclonal antibody to immunoprecipitate RIPE3b1 DNA binding activity. We discuss how tyrosine phosphorylation, a very rare and highly significant regulatory modification, may control RIPE3b1 activator function.
Happiness, Economics and Public Policy: a critique : Review article on “Happiness, Economics and Public Policy” by Helen Johns and Paul Ormerod

textabstractIf politicians and their advisers want to promote the well-being or happiness of citizens they have three ways to find out what they should do. (1) They can analyse the behaviour and the decisions of citizens to find out what they want, in other words: they can try to identify their “revealed preferences”. This is common practice in economics. (2) They can analyse the “stated preferences” of people as they express them explicitly in inquiries, referenda, polls and elections. (3) They can analyse the conditions that make people happy by comparing the conditions of people at different levels of happiness. Economists, like Helen Johns and Paul Ormerod, have an outspoken preference for the first option and they are sceptical about the third. Their argument is unbalanced because they are too critical about the authenticity and complexity of self-reported happiness and not critical enough about the authenticity and complexity of revealed preferences. Economists should appreciate the comparative advantages and additional value of each option and try to find optimal combinations with synergistic effects. Economists should appreciate happiness research as an option to assess the nature and magnitude of “externalities” within their own discipline.
NF‐κB pathway: a target for preventing β‐amyloid (Aβ)‐induced neuronal damage and Aβ42 production

Beta‐amyloid (Aβ) peptides are key proteins in the pathophysiology of Alzheimer's disease (AD). While Aβ42 aggregates very rapidly to form early diffuse plaques, supplemental Aβ40 deposition is required to form mature neuritic plaques. We here investigated the role of nuclear factor‐κB (NF‐κB) pathway in Aβ40‐mediated neuronal damage and amyloid pathology. In rat primary neurons and human postmitotic neuronal cells, the Aβ peptide induced a dose‐dependent neuronal death, reduced the levels of the anti‐apoptotic protein Bcl‐XL, enhanced the cytosolic release of cytochrome c, and elicited the intracellular accumulation and secretion of Aβ42 oligomers. Moreover, Aβ40 activated the NF‐κB pathway by selectively inducing the nuclear translocation of p65 and p50 subunits, and promoted an apoptotic profile of gene expression. As inhibitors of the NF‐κB pathway, we tested the capability of a double‐stranded κB decoy oligonucleotide, the anti‐inflammatory drug aspirin and the selective IκB kinase 2 inhibitor, AS602868, to modify the Aβ40‐mediated effects. These treatments, transiently applied before Aβ exposure, completely inhibited p50/p65 nuclear translocation and neuronal damage. The κB decoy also inhibited the Aβ‐induced release of cytochrome c, restored the levels of Bcl‐XL, and prevented intraneuronal accumulation and secretion of Aβ42. These results open up interesting perspectives on the development of novel strategies targeting out NF‐κB p50/p65 dimers for pharmacological intervention in AD.
Genetics of food preferences: a first view from silk road populations.

Food preferences are the main factor driving food intake and choice. There are good reasons to suspect some genetic influence on food acceptance, not least because genetic factors are implicated in a number of factors that are likely to be related to food choice. In addition, some food dislikes show themselves early in life, before there is any evidence for aversive experiences. Although taste has been widely studied in regards of pure tastes such as bitter or sweet perception, the relationship between taste-related genes and food preferences has seldom been explored. In this work we investigated relationship of 37 taste-related genes with food preferences. The study was carried out during a scientific expedition through Caucasus and Central Asia (Silk Road) analyzing more than 400 samples from 5 different countries. A food preference questionnaire was administered to each participant and a DNA sample was obtained. Other information, such as age, sex, life style and anthropometrical measures, were also collected. We found significant associations with variants of: (1) TAS1R2 [Correction added after initial online publication on 27 Aug 2012. TAS1R3 was changed to TAS1R2. ] gene and liking of Vodka (P= 1.6 × 10(-3)), white wine (P= 4.0 × 10(-4)) and lamb meat (P= 1.6 × 10(-3)); (2) PCLB2 gene and preference for Hot Tea (P= 8.0 × 10(-4)); (3) TPRV1 gene and beet liking (P= 3.8 × 10(-5)); and (4) ITPR3 gene and liking of both lamb meat (5.8 × 10(-4)) and sheep cheese (8.9×10(-4)). These findings give a new insight on a better understanding, of genetic factors influencing food preferences which is critical to the development of effective dietary interventions, especially for people that may be genetically not predisposed for liking specific nutrients.
WristAuthen: A Dynamic Time Wrapping Approach for User Authentication by Hand-Interaction through Wrist-Worn Devices

The growing trend of using wearable devices for context-aware computing and pervasive sensing systems has raised its potentials for quick and reliable authentication techniques. Since personal writing habitats differ from each other, it is possible to realize user authentication through writing. This is of great significance as sensible information is easily collected by these devices. This paper presents a novel user authentication system through wrist-worn devices by analyzing the interaction behavior with users, which is both accurate and efficient for future usage. The key feature of our approach lies in using much more effective Savitzky-Golay filter and Dynamic Time Wrapping method to obtain fine-grained writing metrics for user authentication. These new metrics are relatively unique from person to person and independent of the computing platform. Analyses are conducted on the wristband-interaction data collected from 50 users with diversity in gender, age, and height. Extensive experimental results show that the proposed approach can identify users in a timely and accurate manner, with a false-negative rate of 1.78\%, false-positive rate of 6.7\%, and Area Under ROC Curve of 0.983 . Additional examination on robustness to various mimic attacks, tolerance to training data, and comparisons to further analyze the applicability.
Update in airway stents.

PURPOSE OF REVIEW Malignant central airway obstruction heavily impacts patients' quality of life and its management continues to be a challenge. The current article will review the use of airway stents in this population. RECENT FINDINGS Airway stenting is highly effective in palliating symptoms of airway obstruction. There are several types of stents available with different advantages and disadvantages depending mainly on the material they are made from. Clinical outcomes seem to be comparable between silicone and self-expanding metal stents. Self-expanding metal stents have proven to be efficient in recanalizing 'complex' central airway obstructions. Preliminary data show that a new self-expanding 'hybrid' stent appears to be effective and safe for malignant airway obstruction. Airway stent complications vary according to the type of stent and the type of obstruction. Multidetector computed tomography seems to be a valuable adjunct to bronchoscopy in detecting and characterizing stent complications. A clear definition of airway stent-related infection is urgently needed to provide adequate diagnosis and management of this complication. Metal stent fracture is less common in patients with malignant airway obstruction as compared with benign disease, and this could be partially explained by the decreased survival and shorter exposure to stent in the former population. SUMMARY Airway stents are of great help in palliating symptoms of malignant central airway obstruction. Unfortunately, there have been no recent striking advances in stent technology and the ideal stent has yet to be designed.
Empirical Awakening: The New Science on Mutual Help and Implications for Cost Containment under Health Care Reform

Over the past 75 years, Alcoholics Anonymous (AA) has grown from 2 members to over 2 million members. AA and similar organizations (e.g., Narcotics Anonymous [NA]) are among the most commonly sought sources of help for substance-related problems in the United States. It is only relatively recently, however, that the scientific community has conducted rigorous studies on the clinical utility and health care cost-offset potential of mutual-help groups and developed and tested professional treatments to facilitate their use. As a result of this research, AA as an organization has experienced an “empirical awakening,” evolving from its peripheral status as a “nuisance variable” and perceived obstacle to progress to playing a more central role in a scientifically informed recovery oriented system of care. Also, professionally delivered interventions designed to facilitate the use of AA and NA (“Twelve-Step Facilitation” [TSF]) are now “empirically supported treatments” as defined by US federal agencies and the American Psychological Association. Under the auspices of health care reform, a rational societal response to the prodigious health and social burden posed by alcohol and other drug misuse should encompass the implementation of empirically based strategies (e.g., TSF) in order to maximize the use of ubiquitous mutual-help recovery resources.
Systemic cytokine response in pigs infected orally with a Lawsonia intracellularis isolate of South Korean origin

In the swine industry, Lawsonia intracellularis is one of the main enteric pathogens; it causes acute intestinal hemorrhage (proliferative hemorrhagic enteropathy) in naïve adult pigs and a wasting disease (proliferative enteropathy) in growing pigs. Among many kinds of cytokines, interferon-γ (IFN-γ) has previously been reported to play a significant role in limiting intracellular infection and increasing cellular proliferation associated with L. intracellularis. However, the levels of various circulating inflammatory cytokines, including IFN-γ, in animals infected with L. intracellularis is still an area of considerable interest for understanding immunity against this bacterium. In addition, there has been no information on cytokine response in animals infected with any L. intracellularis isolate of South Korean origin or Asian origin. To determine the relationship between the changes in the systemic inflammatory cytokine response in the peripheral blood of the host after L. intracellularis infection, we measured the levels of some pro-inflammatory cytokines such as tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and IFN-γ), anti-inflammatory cytokines (IL-4, IL-10, and transforming growth factor-β (TGF-β)), and a chemokine (IL-8) in pigs infected with L. intracellularis isolated from South Korea. This study demonstrated that a L. intracellularis isolate of South Korean origin induced cytokine (TNF-α, IL-6, and IFN-γ) responses in infected animals within 15 days post-infection although the circulating levels of IL-4, IL-10, IL-8 and TGF-β were induced relatively late.
Effect of inhalation of different mixtures of O2 and CO2 on retinal blood flow

Aim: To determine the effects of various mixtures of O2 and CO2 on retinal blood flow in healthy subjects. Methods: A randomised, double masked, four way crossover trial was carried out in 12 healthy male non-smoking subjects. Gas mixtures (100% O2, 97.5% O2 + 2.5% CO2, 95% O2 + 5% CO2, and 92% O2 + 8% CO2) were administered for 10 minutes each. Two non-invasive methods were used: laser Doppler velocimetry (LDV) for measurement of retinal blood velocity and fundus imaging with the Zeiss retinal vessel analyser (RVA) for the assessment of retinal vessel diameters. Arterial pH, pCO2, and pO2 were determined with an automatic blood gas analysis system. Retinal blood flow through a major temporal vein was calculated. Results: Retinal blood velocity, retinal vessel diameter, and retinal blood flow decreased during all breathing periods (p <0.001 each). Administration of 92% O2 + 8% CO2 significantly increased SBP, MAP, and PR (p <0.001 each, versus baseline), whereas the other gas mixtures had little effect on systemic haemodynamics. Addition of 2.5%, 5%, and 8% CO2 to oxygen caused a marked decrease in pH and an increase in pCO2 (p <0.001 versus pure oxygen). Conclusions: Breathing of pure oxygen and oxygen in combination with carbon dioxide significantly decreases retinal blood flow. Based on these data the authors speculate that hyperoxia induced vasoconstriction is not due to changes in intravascular pH and cannot be counteracted by an intravascular increase in pCO2.
The effect of nerve lesions on the inflammatory response to injury

The effects of surgical denervation, capsaicin, and 6‐Hydroxydopamine pretreatment on the inflammatory response to thermal injury have been investigated in the rat. Surgical denervation and capsaicin pretreatment reduced the cellular and exudative reactions to the injury. 6‐Hydroxydopamine appeared to have a selective effect on the exudative reaction only. The effects of surgical denervation are partly explained by local and systemic effects of the procedure.
Lipopolysaccharide Modulation of Dendritic Cells Is Insufficient to Mature Dendritic Cells to Generate CTLs from Naive Polyclonal CD8+ T Cells In Vitro, Whereas CD40 Ligation Is Essential1

Many cytotoxic CD8+ T cell responses are dependent on the interactions between CD40 ligand on the helper CD4+ T cell and CD40 on the APC. Although CD40 triggering of dendritic cells (DC) has been shown to mature the DC by increasing the level of expression of costimulatory molecules and inducing IL-12 secretion, the precise mechanisms by which CD40-CD40 ligand interactions allow DC to drive CTL responses remain unknown. We have used an in vitro model in which naive polyclonal CD8+ T cells can be activated by bone marrow-derived DC to investigate factor(s) that are responsible for this CD40-dependent generation of CTLs. DC modulated with agonistic anti-CD40 mAb (aCD40) are able to generate Ag-specific CTL responses while DC modulated with the microbial stimulus LPS alone do not. We compared the Ag-presenting capacity, levels of costimulatory molecules, and release of cytokines and chemokines of DC modulated with aCD40 to that of DC modulated by LPS. None of the factors assayed account for the unique capacity of anti-CD40-matured DC to drive CTL but this model provides a simplified system for further investigation. Although we attempted to use an LPS-free system for these studies, we are unable to rule out the possibility that very low levels of endotoxin (<20 pg/ml) may synergize with CD40 ligation in the generation of CTLs.
Quantification assessment of bradykinesia in Parkinson's disease based on a wearable device

Bradykinesia is one of the primary characteristic symptoms of Parkinson's disease (PD). Ten-second whole-hand-grasps action was chosen to assess bradykinesia severity in this study. A quantification assessment system based on a self-developed wearable device was proposed to assess the severity of the parkinsonian bradykinesia. The proposed assessment method used an attitude-estimation algorithm to extract the parkinsonian bradykinesia parameters. A regression model was adopted to fit the characteristic parameters with the clinical UPDRS ratings judged by neurologists. Clinical experiment with 15 PD patients and 5 age-matched healthy controls demonstrated that the predicted bradykinesia scores by proposed model correlated well with the judgments of neurologists (r2=0.99). The proposed quantification model demonstrated the greater goodness-of-fit compared with the related works.
Bone marrow-derived mesenchymal stem cells in fibrin augment angiogenesis in the chronically infarcted myocardium.

AIMS Current efforts to treat myocardial infarction include the delivery of cells and matrix scaffolds. Bone marrow-derived mesenchymal stem cells (BM-MSCs) are multipotent stem cells that secrete angiogenic growth factors, and fibrin has been shown to be a biomaterial that provides structural support to cells and tissues. The objective of this study was to characterize the attachment and viability of BM-MSCs in fibrin in vitro, and then to assess the efficacy of treatment with BM-MSCs in fibrin for promoting neovascularization in the chronically infarcted myocardium. MATERIALS & METHODS BM-MSCs were cultured in fibrin and assessed for cell attachment and viability by using immunofluorescence staining for actin filaments and Live/Dead((R)) viability assays, respectively. To determine the efficacy of BM-MSCs in fibrin in vivo, chronically infarcted rat hearts were treated with either cells, cells in fibrin, fibrin or saline (n = 9). After 5 weeks, the infarct scar tissues were assessed for neovascularization. RESULTS BM-MSCs exhibited robust cell attachment and viability when cultured in fibrin in vitro. Furthermore, when injected together into the infarcted tissue, BM-MSCs in fibrin could enhance neovasculature formation by increasing capillary density, in comparison to treatment by cells or fibrin separately. Concomitant to significant improvement in capillary density was an increase in the levels of VEGF in the infarct scar. CONCLUSION This study demonstrates the angiogenic potential of the combined delivery of BM-MSCs and fibrin, and highlights the advantage of stem cell-matrix approaches for myocardial repair.
Achieving physical layer security with massive MIMO beamforming

Physical layer security allows secure communications between a source and destination without the need to resort to key-based encryption techniques. Its increasing importance stems from the difficulty of implementing advanced encryption techniques in certain networks, such as the internet of things (IoT). In this paper, physical layer security is implemented by using massive multiple input multiple output (MIMO) techniques. Specifically, beamforming with large cylindrical antenna arrays is investigated. These arrays allow the transmission of both the useful signal to the destination and the jamming signal to the eavesdropper without resorting to the help of other nodes for relaying the signal and/or jamming the eavesdropper. Simulation results show that high levels of secrecy capacity can be achieved with the proposed approach.
Cardiac metabolic adaptations in response to chronic hypoxia

Since a constant supply of oxygen is essential to sustain life, organisms have evolved multiple defence mechanisms to ensure maintenance of the delicate balance between oxygen supply and demand. However, this homeostatic balance is perturbed in response to a severe impairment of oxygen supply, thereby activating maladaptive signalling cascades that result in cardiac damage. Past research efforts have largely focused on determining the pathophysiological effects of severe lack of oxygen. By contrast, and as reviewed here, exposure to moderate chronic hypoxia may induce cardioprotective properties. The hypothesis put forward is that chronic hypoxia triggers regulatory pathways that mediate long‐term cardiac metabolic remodelling, particularly at the transcriptional level. The novel proposal is that exposure to chronic hypoxia triggers (a) oxygen‐sensitive transcriptional modulators that induce a switch to increased carbohydrate metabolism (fetal gene programme) and (b) enhanced mitochondrial respiratory capacity to sustain and increase efficiency of mitochondrial energy production. These compensatory protective mechanisms preserve contractile function despite hypoxia.
SufU Is an Essential Iron-Sulfur Cluster Scaffold Protein in Bacillus subtilis

ABSTRACT Bacteria use three distinct systems for iron-sulfur (Fe/S) cluster biogenesis: the ISC, SUF, and NIF machineries. The ISC and SUF systems are widely distributed, and many bacteria possess both of them. In Escherichia coli, ISC is the major and constitutive system, whereas SUF is induced under iron starvation and/or oxidative stress. Genomic analysis of the Fe/S cluster biosynthesis genes in Bacillus subtilis suggests that this bacterium's genome encodes only a SUF system consisting of a sufCDSUB gene cluster and a distant sufA gene. Mutant analysis of the putative Fe/S scaffold genes sufU and sufA revealed that sufU is essential for growth under minimal standard conditions, but not sufA. The drastic growth retardation of a conditional mutant depleted of SufU was coupled with a severe reduction of aconitase and succinate dehydrogenase activities in total-cell lysates, suggesting a crucial function of SufU in Fe/S protein biogenesis. Recombinant SufU was devoid of Fe/S clusters after aerobic purification. Upon in vitro reconstitution, SufU bound an Fe/S cluster with up to ∼1.5 Fe and S per monomer. The assembled Fe/S cluster could be transferred from SufU to the apo form of isopropylmalate isomerase Leu1, rapidly forming catalytically active [4Fe-4S]-containing holo-enzyme. In contrast to native SufU, its D43A variant carried a Fe/S cluster after aerobic purification, indicating that the cluster is stabilized by this mutation. Further, we show that apo-SufU is an activator of the cysteine desulfurase SufS by enhancing its activity about 40-fold in vitro. SufS-dependent formation of holo-SufU suggests that SufU functions as an Fe/S cluster scaffold protein tightly cooperating with the SufS cysteine desulfurase.
Healing under pressure: hyperbaric oxygen and myocutaneous flap repair for extreme persistent perineal sinus after proctectomy for inflammatory bowel disease

Persistent perineal sinus (PPS) following proctectomy for inflammatory bowel disease affects about 50% of patients. Up to 33% of cases of PPS remain unhealed at 12 months and the most refractory cases are unhealed at 24 months despite optimal conventional therapy. Reports of hyperbaric oxygen therapy (HBOT) for chronic wounds and Crohn's perianal disease led us to explore perioperative HBOT with rectus abdominis myocutaneous (RAM) flap repair in a highly selected group of patients with extreme PPS who had failed all other interventions.