Miracle-dz/UniFAR-FTUs huggingface dataset:
Role of calcium-induced mitochondrial hydroperoxide in induction of apoptosis of RBL2H3 cells with eicosapentaenoic acid treatment

Eicosapentaenoic acid (EPA) was previously shown to induce caspase-independent apoptosis in rat basophilic leukemia cells (RBL2H3 cells) by translocation of apoptosis-inducing factor (AIF) [Free Radic Res (2005) 39, 225–235]. Here, we attempted to investigate the mechanism of EPA-induced apoptosis. A rapid and sustained increase in calcium was observed in mitochondria at 2 h after the addition of EPA prior to apoptosis. Coincidently, hydroperoxide was generated in the mitochondria after exposure to EPA. Production of mitochondrial hydroperoxide was significantly reduced by ruthenium red, an inhibitor of mitochondrial calcium uniporter, and BAPTA-AM, a cytoplasmic calcium chelator, indicating that generation of hydroperoxide is triggered by an accumulation of calcium in the mitochondria. The production of mitochondrial hydroperoxide was markedly attenuated by overexpression of phospholipid hydroperoxide glutathione peroxidase (PHGPx) in the mitochondria. Apoptosis was therefore, significantly prevented through inhibition of mitochondrial hydroperoxide generation with mitochondrial PHGPx, ruthenium red or BAPTA-AM. However, accumulation of calcium in the mitochondria was not prevented by mitochondrial PHGPx although apoptosis was blocked, indicating that elevated calcium does not directly induce apoptosis. Taken together, our results show that calcium-dependent hydroperoxide accumulation in the mitochondria is critical in EPA-induced apoptosis.
High Affinity Binding between Lipoprotein Lipase and Lipoproteins Involves Multiple Ionic and Hydrophobic Interactions, Does Not Require Enzyme Activity, and Is Modulated by Glycosaminoglycans*

Lipoprotein lipase (LPL) physically associates with lipoproteins and hydrolyzes triglycerides. To characterize the binding of LPL to lipoproteins, we studied the binding of low density lipoproteins (LDL), apolipoprotein (apo) B17, and various apoB-FLAG (DYKDDDDK octapeptide) chimeras to purified LPL. LDL bound to LPL with high affinity (K d values of 10−12 m) similar to that observed for the binding of LDL to its receptors and 1D1, a monoclonal antibody to LDL, and was greater than its affinity for microsomal triglyceride transfer protein. LDL-LPL binding was sensitive to both salt and detergents, indicating the involvement of both hydrophobic and hydrophilic interactions. In contrast, the N-terminal 17% of apoB interacted with LPL mainly via ionic interactions. Binding of various apoB fusion peptides suggested that LPL bound to apoB at multiple sites within apoB17. Tetrahydrolipstatin, a potent enzyme activity inhibitor, had no effect on apoB-LPL binding, indicating that the enzyme activity was not required for apoB binding. LDL-LPL binding was inhibited by monoclonal antibodies that recognize amino acids 380–410 in the C-terminal region of LPL, a region also shown to interact with heparin and LDL receptor-related protein. The LDL-LPL binding was also inhibited by glycosaminoglycans (GAGs); heparin inhibited the interactions by ∼50% and removal of trace amounts of heparin from LPL preparations increased LDL binding. Thus, we conclude that the high affinity binding between LPL and lipoproteins involves multiple ionic and hydrophobic interactions, does not require enzyme activity and is modulated by GAGs. It is proposed that LPL contains a surface exposed positively charged amino acid cluster that may be important for various physiological interactions of LPL with different biologically important molecules. Moreover, we postulate that by binding to this cluster, GAGs modulate the association between LDL and LPL and the in vivo metabolism of LPL.
Variability in Activity May Precede Diabetic Foot Ulceration: Response to LeMaster, Mueller, and Sinacore

We greatly appreciate the opportunity to reply to the very thoughtful and insightful letter by LeMaster, Mueller, and Sinacore (1). We believe that the comments raised are very important and deserve this sort of forum. As to the first suggestion that waist-mounted accelerometers may not be robust enough to capture short shuffling steps taken by many of our less active patients with diabetes, our only response is that we agree. While the devices we used were highly sensitive and could be very finely calibrated, they do not approach the ability of ankle-worn devices to capture very …
Sister Earth, Our Common Home: Toward a Sustainable, Planet Friendly Approach to Dialysis, a Paradigm of High Technology Medicine.

In our high-technology, highly polluted world, medicine plays an important role balancing saving lives with the expenses of growing amounts of waste products, not only biologically dangerous (the potentially "contaminated" or "hazardous" waste) but also potentially harmful for the planet (nonrecyclable, plastic waste). Dialysis, the prototype of high-technology medicine, is central to these problems, as the present treatment of about 2 million patients produces an enormous quantity of waste (considering hazardous waste only about 2 kg per session, with 160 sessions per year, that is 320 kg per patient, or about 640,000 tons of hazardous waste per year for 2 million patients, roughly corresponding to 6 nuclear aircraft carriers). Furthermore, obsolete dialysis machines, and water treatments are discharged, adding to the "technological waste. " Water produced by the reverse osmosis is also discharged; this is the only nonhazardous, nonpolluting waste, but in particular in dry areas, wasting water is a great ecologic concern. The present review is aimed at discussing strategies already in place and to be further implemented for reducing this particular "uremic toxin" for the earth: dialysis waste, including dialysis disposables, water, and dialysis machines.
Brain Cytokines and the 5‐HT System during Poly I:C‐Induced Fatigue

Abstract: Fatigue is evoked not only by peripheral factors, such as muscle fatigue, but also by the central nervous system (CNS). For example, it is generally known that the feeling of fatigue is greatly influenced by psychological aspects, such as motivation. However, little is known about the central mechanisms of fatigue. The clinical symptoms of chronic fatigue syndrome (CFS) are shown to include disorders in neuroendocrine, autonomic, and immune systems. On the other hand, it has been demonstrated that cytokines produced in the brain play significant roles in neural–immune interactions through their various central actions, including hypothalamo‐pituitary and sympathetic activation, as well as immunosuppression. In this article, using the immunologically induced fatigue model, which was achieved by intraperitoneal (i.p.) injection of synthetic double‐stranded RNAs, polyriboinosinic: polyribocytidylic acid (poly I:C) in rats, we show an involvement of brain interferon‐α (IFN‐α) and serotonin (5‐HT) transporter (5‐HTT) in the central mechanisms of fatigue. In the poly I:C‐induced fatigue rats, expression of IFN‐α and 5‐HTT increased, while extracellular concentration of 5‐HT in the medial prefrontal cortex decreased, probably on account of the enhanced expression of 5‐HTT. Since the poly I:C‐induced reduction of the running wheel activity was attenuated by a 5‐HT1A receptor agonist, but not by 5‐HT2, 5‐HT3, or dopamine D3 receptor agonists, it is suggested that the decrease in 5‐HT actions on 5‐HT1A receptors may at least partly contribute to the poly I:C‐induced fatigue.
The sparse discrete cosine transform with application to image compression

Presented here is a description and analysis of the N-point sparse discrete cosine transform (SDCT), where N is a power of two, which retains all of the properties of the parent DCT such as linearity, energy compaction, and having a fast transform implementation, while allowing arbitrarily-many known zeros, i.e., masked elements, in the input. It has application to image and video compression in that arbitrarily shaped regions may be transformed by the two-dimensional (2D) SDCT with approximately the same resulting compression efficiency as the standard 2D DCT applied to square blocks. The solution is based on a systematic application of symmetry and additive symmetry to the input elements. The four- and eight-point solutions are presented first, with emphasis on development of a set of generating matrices, and finally a general N-point solution is described. The 8×8 SDCT was implemented in VP9 and as expected the transform was found to be perfect and also improved compression efficiency for video objects with a known mask.
Fusion gene-negative alveolar rhabdomyosarcoma is clinically and molecularly indistinguishable from embryonal rhabdomyosarcoma.

PURPOSE To determine whether the clinical and molecular biologic characteristics of the alveolar rhabdomyosarcoma (ARMS) and embryonal rhabdomyosarcoma (ERMS) subtypes have relevance independent of the presence or absence of the PAX/FOXO1 fusion gene. PATIENTS AND METHODS The fusion gene status of 210 histopathologically reviewed, clinically annotated rhabdomyosarcoma samples was determined by reverse transcriptase polymerase chain reaction. Kaplan-Meier analysis was used to assess event-free survival and overall survival in fusion gene-negative ARMS (ARMSn; n = 39), fusion gene-positive ARMS (ARMSp; n = 94), and ERMS (n = 77). A total of 101 RMS samples were also profiled for whole-genome expression, and 128 were profiled for genomic copy number imbalances. Profiling data were analyzed by supervised and unsupervised methods to compare features related to histopathology and fusion gene status. Results were also projected by meta-analysis techniques across three separate publically available data sets. RESULTS Overall and event-free survival, frequency of metastases, and distribution of site at initial presentation were not significantly different between ARMSn and ERMS. Consistent with this, analysis of gene expression signatures could not reproducibly distinguish ARMSn from ERMS whereas fusion gene-positive cases were distinct. ARMSn and ERMS frequently show whole-chromosome copy number changes, notably gain of chromosome 8 with associated high levels of expression of genes from this chromosome. CONCLUSION The clinical behavior and molecular characteristics of alveolar cases without a fusion gene are indistinguishable from embryonal cases and significantly different from fusion-positive alveolar cases. This implies that fusion gene status irrespective of histology is a critical factor in risk stratification of RMS.
Role of nonrandomly oriented cell division in shaping and bending of the neural plate

Neural plate shaping and bending are crucial to the process of neural tube formation. Shaping requires intrinsic forces generated by alterations in neuroepithelial cell behavior, whereas bending requires similar intrinsic forces and extrinsic forces generated by alterations in cell behaviors outside the neural plate. This study evaluates the role of nonrandomly oriented cell division in neural plate shaping and epidermal ectoderm expansion during bending by examining mitotic spindle orientation in the neuroepithelium and epidermal ectoderm throughout neurulation. Neuroepithelial mitotic spindles are oriented preferentially in the rostrocaudal plane, suggesting a role for nonrandomly oriented (i.e., rostrocaudal) neuroepithelial cell division in longitudinal lengthening of the neural plate during shaping. Epidermal ectoderm mitotic spindles are oriented preferentially in both rostrocaudal and mediolateral planes, suggesting a role for nonrandomly oriented cell division in epidermal ectoderm elongation and expansion. In neural plate and epidermal ectoderm isolates separated prior to shaping and bending, mitotic spindles continued to be oriented preferentially in the rostrocaudal plane; however, a preferential mediolateral mitotic spindle orientation could not be demonstrated in the epidermal ectoderm isolates. We conclude that the nonrandom rostrocaudal orientation of cell division in the neuroepithelium and epidermal ectoderm is an autonomous process, occurring in the absence of forces from adjacent tissues, whereas the nonrandom mediolateral orientation of cell division in the epidermal ectoderm is dependent upon interactions with the neural plate. J. Comp. Neurol. 381:473‐488, 1997. © 1997 Wiley‐Liss, Inc.
A Randomized, Prospective Study of Operative and Non-Operative Treatment of Injuries of the Fibular Collateral Ligaments of the Ankle*

One hundred and forty-six adults who had an isolated injury of the fibular collateral ligaments of the ankle were randomized to be managed operatively or non-operatively. Disruption of the ligaments was diagnosed by means of a physical examination and on the basis of stress radiographs of the ankle made with use of a specially designed device to hold the leg. Operative treatment, performed in seventy-three patients, consisted of suture repair of the disrupted ligaments within seventy-two hours after the injury, followed by immobilization of the ankle in a below-the-knee plaster cast for six weeks. Non-operative treatment, used for seventy-three patients, consisted of the use of an ankle orthosis for six weeks. After a minimum of two years of follow-up, we could detect no significant differences, with the numbers available, between the two groups with regard to the functional result or the degree of joint laxity that was evident on stress radiographs. The non-operative group lost a mean of 1.6 weeks from work, and the operative group lost a mean of 7.0 weeks. We concluded that non-operative treatment of an injury of the fibular collateral ligaments of the ankle yields results that are comparable with those of operative repair and is associated with a shorter period of recovery.
Influence of Cyclooxygenase‐2 (COX‐2) Gene Promoter Polymorphism −765 on Graft Loss After Renal Transplantation

A G→C polymorphism has been identified in the human cyclooxygenase‐2 (COX‐2) gene promoter at position −765 with C allele leading to a decreased promoter activity with low prostaglandin E2 (PGE2) production. PGE2 has strong immunomodulatory properties that could influence graft survival. We studied the association between this polymorphism and allograft failure in two independent cohorts of renal transplant recipients (RTRs) including a total of 603 patients. The functional effect of COX‐2 gene promoter polymorphism was analyzed by measuring serum levels of PGE2. Median follow‐up was 8.7 and 7.9 years for the first and second cohort, respectively. Analysis of 603 patients identified 20 CC (3.3%), 179 GC (29.7%) and 404 GG (67%) carriers. Patients with the GG genotype had significantly higher serum PGE2 concentrations than patients with the C allele. Carriers with a C allele have an independent increased risk of graft loss (hazard ratio (HR) 2.43 [95% CI 1.19–4.97], p = 0.015 for cohort 1; HR 1.72 [95% CI 0.99–3.77], p = 0.051 for cohort 2) compared to GG patients. COX‐2 gene promoter polymorphism at position −765 (G→C) is associated with a higher rate of graft loss in RTRs. Such findings may be used to influence immunosuppressive strategies and optimize patient management.
Morality, Space, and the Power of Wind‐Energy Landscapes

Most of us have not known—or cared—where our electricity comes from. Our attitude is changing, however, as we turn toward wind energy, now the fastest‐growing renewable energy resource in the world. Because we cannot extract and transport the raw energy of the wind, reaping its many environmental benefits requires that we cope with the landscape presence of its development wherever it occurs. Sometimes this interferes with the value of open space, and sometimes it may be close to subdivisions. It is the immobility and very visibility of wind power that makes its presence unavoidable. In that regard it cannot be hidden underground, stored in tanks, or moved by trains. It is an energy resource that reminds us that our electricity comes from somewhere. The more we wish to tap the power of the wind, the less we will be able to avoid the responsibilities that our demand for energy brings. This necessary bargain, first evident near Palm Springs, California, is now being experienced wherever wind power is being developed.
Yeast Rpi1 Is a Putative Transcriptional Regulator That Contributes to Preparation for Stationary Phase

ABSTRACT The RPI1 gene of Saccharomyces cerevisiae was identified initially as a dosage suppressor of the heat shock sensitivity associated with overexpression of RAS2 (J. Kim and S. Powers, Mol. Cell. Biol. 11:3894–3904, 1991). Based on its failure to suppress mutationally activated RAS2, RPI1 was proposed to be a negative regulator of the Ras/cyclic AMP (cAMP) pathway that functions at a point upstream of Ras. We isolated RPI1 as a high-copy-number suppressor of the cell lysis defect associated with a null mutation in the MPK1 gene, which encodes the mitogen-activated protein kinase of the cell wall integrity-signaling pathway. Although the sequence of Rpi1 is not informative about its function, we present evidence that this protein resides in the nucleus, possesses a transcriptional activation domain, and affects the mRNA levels of several cell wall metabolism genes. In contrast to the previous report, we found that RPI1 overexpression suppresses defects associated with mutational hyperactivation of the Ras/cAMP pathway at all points including constitutive mutations in the cAMP-dependent protein kinase. We present additional genetic and biochemical evidence that Rpi1 functions independently of and in opposition to the Ras/cAMP pathway to promote preparations for the stationary phase. Among these preparations is a fortification of the cell wall that is antagonized by Ras pathway activity. This observation reveals a novel link between the Ras/cAMP pathway and cell wall integrity. Finally, we propose that inappropriate expression of RPI1 during log phase growth drives fortification of the cell wall and that this behavior is responsible for suppression of the mpk1 cell lysis defect.
Effect of isoniazid prophylaxis on mortality and incidence of tuberculosis in children with HIV: randomised controlled trial

Objectives To investigate the impact of isoniazid prophylaxis on mortality and incidence of tuberculosis in children with HIV. Design Two centre prospective double blind placebo controlled trial. Participants Children aged ≥8 weeks with HIV. Interventions Isoniazid or placebo given with co-trimoxazole either daily or three times a week. Setting Two tertiary healthcare centres in South Africa. Main outcome measures Mortality, incidence of tuberculosis, and adverse events. Results Data on 263 children (median age 24.7 months) were available when the data safety monitoring board recommended discontinuing the placebo arm; 132 (50%) were taking isoniazid. Median follow-up was 5.7 (interquartile range 2.0-9.7) months. Mortality was lower in the isoniazid group than in the placebo group (11 (8%) v 21 (16%), hazard ratio 0.46, 95% confidence interval 0.22 to 0.95, P=0.015) by intention to treat analysis. The benefit applied across Centers for Disease Control clinical categories and in all ages. The reduction in mortality was similar in children on three times a week or daily isoniazid. The incidence of tuberculosis was lower in the isoniazid group (5 cases, 3.8%) than in the placebo group (13 cases, 9.9%) (hazard ratio 0.28, 0.10 to 0.78, P=0.005). All cases of tuberculosis confirmed by culture were in children in the placebo group. Conclusions Prophylaxis with isoniazid has an early survival benefit and reduces incidence of tuberculosis in children with HIV. Prophylaxis may offer an effective public health intervention to reduce mortality in such children in settings with a high prevalence of tuberculosis. Trial registration. Clinical Trials NCT00330304
Low-density lipoprotein receptor-related protein 5 (LRP5) is essential for normal cholesterol metabolism and glucose-induced insulin secretion

A Wnt coreceptor low-density lipoprotein receptor-related protein 5 (LRP5) plays an essential role in bone accrual and eye development. Here, we show that LRP5 is also required for normal cholesterol and glucose metabolism. The production of mice lacking LRP5 revealed that LRP5 deficiency led to increased plasma cholesterol levels in mice fed a high-fat diet, because of the decreased hepatic clearance of chylomicron remnants. In addition, when fed a normal diet, LRP5-deficient mice showed a markedly impaired glucose tolerance. The LRP5-deficient islets had a marked reduction in the levels of intracellular ATP and Ca2+ in response to glucose, and thereby glucose-induced insulin secretion was decreased. The intracellular inositol 1,4,5-trisphosphate (IP3) production in response to glucose was also reduced in LRP5−/− islets. Real-time PCR analysis revealed a marked reduction of various transcripts for genes involved in glucose sensing in LRP5−/− islets. Furthermore, exposure of LRP5+/+ islets to Wnt-3a and Wnt-5a stimulates glucose-induced insulin secretion and this stimulation was blocked by the addition of a soluble form of Wnt receptor, secreted Frizzled-related protein-1. In contrast, LRP5-deficient islets lacked the Wnt-3a-stimulated insulin secretion. These data suggest that Wnt/LRP5 signaling contributes to the glucose-induced insulin secretion in the islets.
The effect of exercise and training status on platelet activation: Do cocoa polyphenols play a role?

Sedentary and trained men respond differently to the same intensity of exercise, this is probably related to their platelet reactivity and antioxidant capacity. There is growing interest in the utilization of antioxidant-rich plant extracts as dietary food supplements. The aim of this study was to investigate the effect of an acute bout of sub maximal exercise on platelet count and differential response of platelet activation in trained and sedentary subjects and to observe if cocoa polyphenols reverse the effect of exercise on platelet function. The practical significance of this study was that many sedentary people engage in occasional strenuous exercise that may predispose them to risk of heart disease. Fasting blood samples were collected from 16 male subjects, pre and post 1-h cycling exercise at 70% of maximal aerobic power (VO2max) before and after consumption of cocoa or placebo. Agonist stimulated citrated whole blood was utilized for measuring platelet aggregation, adenosine triphosphate (ATP) release and platelet activation. Baseline platelet count (221 ± 33 × 109/L) and ATP release (1.4 ± 0.6 nmol) increased significantly (P < 0.05) after exercise in all subjects. Baseline platelet numbers in the trained were higher (P < 0.05) than in the sedentary (235 ± 37 vs. 208 ± 34 × 109/L), where as platelet activation in trained was lower (P < 0.05) than sedentary (51 ± 6 vs. 59 ± 5%). Seven days of cocoa polyphenol supplementation had little effect on any of the parameters measured. We conclude that trained subjects show decreased activation of stimulated platelets when compared to the sedentary subjects and short-term cocoa polyphenol supplementation did not decrease platelet activity in response to exercise independent of prior training status.
A better heuristic for the minimum connected dominating set in ad hoc networks

Since no fixed infrastructure and no centralized management present in Wireless Ad Hoc Networks (WANETs), a Connected Dominating Set (CDS) representing the network is widely used as a virtual backbone. Given a graph, a CDS is a subset of vertices such that every vertex in the graph is either in the subset or adjacent to a vertex in the subset and the subgraph induced by the subset is connected. A smaller virtual backbone (a smaller size CDS) incurs less communication overhead. However, finding a minimum size CDS is NP-hard. Thus, it is important to design effective algorithms for the minimum CDS (MCDS) problem. In this article, a new efficient heuristic name as 2-Lenght Betweenness Heuristic for the MCDS problem is proposed. Comprehensive simulation results demonstrate that the proposed heuristic algorithm finds better solutions than the existing approach.