Miracle-dz/UniFAR-FTUs huggingface dataset:
The expanding role of mitochondria in apoptosis.

The initial insight into the genetic basis of apoptosis, or programmed cell death, was gained from ingenious studies of the roundworm Caenorhabditis elegans (for review, see Horvitz 1999). These studies revealed a linear pathway whereby the products of two genes, designated Ced-3 andCed-4, were necessary and sufficient to trigger the perfectly timed and orchestrated death of 131 preordained cells during development. The relevance of this pathway to higher animals was established by the discovery of apparent mammalian orthologs of these genes and the demonstration that the mammalian Ced-3-related genes encode proteases (designated caspases) whose activities are responsible for the morphological changes characteristic of apoptosis (for review, see Hengartner 2000). The complexity of the apoptotic program began to increase with the discovery of Bcl-2, a gene whose product causes resistance to apoptosis in lymphocytes (Vaux et al. 1988; McDonnell et al. 1989). Bcl-2 was shown to correct partially the phenotype of a C. elegans mutation in Ced-9, a cell survival gene that functions upstream of Ced-4 and Ced-3 (Vaux et al. 1992). This finding suggested an apparent one-for-one correlation between the C. elegans and mammalian proand antiapoptotic pathways. However, this correlation did not explain two observations made in mammalian cells. First, the Bcl-2 protein was found on the membrane of mitochondria, which were not implicated in C. elegans apoptosis; and second, apoptotic changes could be produced in Xenopus laevis oocyte extracts only when a membrane fraction enriched in mitochondria was present (Hockenberry et al. 1990; Newmeyer et al. 1994). The complex role of mitochondria in mammalian cell apoptosis came into focus when biochemical studies identified several mitochondrial proteins that are able to activate cellular apoptotic programs directly (Liu et al. 1996; Susin et al. 1999; Du et al. 2000; Verhagen et al. 2000; Li et al. 2001). Normally, these proteins reside in the intermembrane space of mitochondria. In response to a variety of apoptotic stimuli, they are released to the cytosol and/or the nucleus. They promote apoptosis either by activating caspases and nucleases or by neutralizing cytosolic inhibitors of this process. A complex picture has emerged in which mitochondrial and cytosolic proapoptotic proteins interact with antiapoptotic proteins with each cell’s life or death hanging in the balance. This review summarizes the recent data on the expanding and complex role of mitochondria in apoptosis.
Comprehensive comparison of health-related quality of life after contemporary therapies for localized prostate cancer.

PURPOSE Health-related quality-of-life (HRQOL) concerns are pivotal in choosing prostate cancer therapy. However, concurrent HRQOL comparison between brachytherapy, external radiation, radical prostatectomy, and controls is hitherto lacking. HRQOL effects of hormonal adjuvants and of cancer control after therapy also lack prior characterization. PATIENTS AND METHODS A cross-sectional survey was administered to patients who underwent brachytherapy, external-beam radiation, or radical prostatectomy during 4 years at an academic medical center and to age-matched controls. HRQOL among controls was compared with therapy groups. Comparison between therapy groups was performed using regression models to control covariates. HRQOL effects of cancer progression were evaluated. RESULTS One thousand fourteen subjects participated. Compared with controls, each therapy group reported bothersome sexual dysfunction; radical prostatectomy was associated with adverse urinary HRQOL; external-beam radiation was associated with adverse bowel HRQOL; and brachytherapy was associated with adverse urinary, bowel, and sexual HRQOL (P < or =.0002 for each). Hormonal adjuvant symptoms were associated with significant impairment (P <.002). More than 1 year after therapy, several HRQOL outcomes were less favorable among subjects after brachytherapy than after external radiation or radical prostatectomy. Progression-free subjects reported better sexual and hormonal HRQOL than subjects with increasing prostate-specific antigen (P <.0001). CONCLUSION Long-term HRQOL after prostate brachytherapy showed no benefit relative to radical prostatectomy or external-beam radiation and may be less favorable in some domains. Hormonal adjuvants can be associated with significant impairment. Progression-free survival is associated with HRQOL benefits. These findings facilitate patient counseling regarding HRQOL expectations and highlight the need for prospective studies sensitive to urinary irritative and hormonal concerns in addition to incontinence, sexual, and bowel HRQOL domains.
Expression of IL‐6 in the ischemic penumbra

We examined the expression of IL-6 within the ischemic penumbra at various time points after transient (3 h) middle cerebral occlusion (MCA-O) in rats. The animals were killed at 1, 3, 7 or 14 days following operation. Coronal brain sections were processed for immunohistochemistry with antibodies against GFAP, OX 42, IL-6 and Nissl-staining. Glial activation within the penumbra started on day one after ischemia and persisted up to day 14. Expression of IL-6 was not present in sham-operated controls. One day after MCA-O there were several IL-6-positive cells in the penumbra. This expression of IL-6 increased on day 3 and remained elevated up to day 14. According to the shape of the IL-6-positive cells they seem to be microglia and neurons. The present results demonstrate a longlasting expression of IL-6 in the ischemic penumbra.
La Ciclovía-Recreativa: Un Programa Masivo de Recreación con Potencial en Salud Pública

Sarmiento esta con el Departamento de Medicina Social, de la Universidad de los Andes, en Bogota, Colombia. Torres y Schmid estan con la Rama de Salud y Actividad Fisica, los Centros de Control y Prevencion para las Enfermedades en Atlanta, GA. Jacoby esta con el Departamento Alimentacion Saludable y Vida Activa, Unidad de Enfermedades No Transmisibles, la Organizacion Panamericana/ Mundial de Salud en Washington, D.C. Pratt esta con el Centro Nacional para la Prevencion de las Enfermedades Cronicas y la Promocion de la Salud, los Centros de Control y Prevencion de las Enfermedades en Atlanta, GA. Stierling esta con la CicloRecreoVia, Club Deportivo en Providencia, Chile. Journal of Physical Activity and Health, 2010, 7(Suppl 2), S163-S180 © 2010 Human Kinetics, Inc.
The endoscopic picture of upper digestive hemorrages secondary to stromal tumors (GIST): report of two cases.

A 74-year-old hypertensive patient with ischemic cardiomyopathy was consulted in the emergency room for experiencing several days of melena like symptoms. Endoscopy was performed, showing a submuscosal tumor around the papillary area. The use of the duodenoscope offered the best view of the tumor, reveling ulceration at its surface (Fig. 1). Ecoendoscopy was able to be done, showing a submuscosal lesion in the second portion of the duodenum (Fig. 2). Areas of necrosis were visible around the interior, solely affecting the muscle layer and leaving the serosa intact. Urgent surgery was performed, extracting the duodenal tumor. The pathological anatomy reported a GIST with a low risk of positive malignance for C-KIT.
MHC class I alleles and their exploration of the antigen‐processing machinery

Summary: At the cell surface, major histocompatibility complex (MHC) class I molecules present fragments of intracellular antigens to the immune system. This is the end result of a cascade of events initiated by multiple steps of proteolysis. Only a small part of the fragments escapes degradation by interacting with the peptide transporter associated with antigen presentation and is translocated into the endoplasmic reticulum lumen for binding to MHC class I molecules. Subsequently, these newly formed complexes can be transported to the plasma membrane for presentation. Every step in this process confers specificity and determines the ultimate result: presentation of only few fragments from a given antigen. Here, we introduce the players in the antigen processing and presentation cascade and describe their specificity and allelic variation. We highlight MHC class I alleles, which are not only different in sequence but also use different aspects of the antigen presentation pathway to their advantage: peptide acquaintance.
The use of biochemical markers of bone turnover in osteoporosis.

OBJECTIVE Present evidence-based recommendations on the use of biochemical markers of bone turnover in the management of osteoporosis. METHODS The English literature from 1999 to 2005 was reviewed by using data sources from MEDLINE. RESULTS Measurement of biochemical markers of bone turnover helps us identify a high bone turnover rate. Elevated levels of these markers points towards a pathology and at an accelerated loss of bone mass. Its main utility is in documenting the response to therapy. They have a limited role in the follow-up of patients with osteoporosis. To be useful, bone markers must be measured at baseline and periodically after the beginning of therapy. A fall of on fifty (50%) percent in the levels of resorption markers between the third and sixth month of therapy predicts a good response. Bone markers can not be used to establish the diagnosis of osteoporosis. Neither do they measure bone mass. Markers are not capable of predicting future loss of bone mass in an individual nor do they correlate with the occurrence of previous fractures. The greatest limitation of these measurements is not being able to measure bone remodeling in the individual subject. Bone resorption markers are more frequently used than those of formation. The levels of the markers can identify the failures to the therapy and responses to therapy. Lack of reduction in the resorption markers could indicate lack of compliance with therapy, problems of absorption of the medication or lack in response to treatment. There may be problems with the measurement and the interpretation of results of bone remodeling markers. Variability between individuals and intra-individual variability exist as well as inter-assay and intra-assay variability. CONCLUSION Biochemical markers of bone turnover along with measurements of bone density can help optimize the management of osteoporosis. The use of the bone markers is not recommended in a routine form, but they can be of utility in situations of poor compliance with the therapy or when there are difficulties in the management of the treatment of osteoporosis.
The Notch ligand Delta-like 4 negatively regulates endothelial tip cell formation and vessel branching

Delta-like 4 (Dll4) is a transmembrane ligand for Notch receptors that is expressed in arterial blood vessels and sprouting endothelial cells. Here we show that Dll4 regulates vessel branching during development by inhibiting endothelial tip cell formation. Heterozygous deletion of dll4 or pharmacological inhibition of Notch signaling using γ-secretase inhibitor revealed a striking vascular phenotype, with greatly increased numbers of filopodia-extending endothelial tip cells and increased expression of tip cell marker genes compared with controls. Filopodia extension in dll4+/− retinal vessels required the vascular growth factor VEGF and was inhibited when VEGF signaling was blocked. Although VEGF expression was not significantly altered in dll4+/− retinas, dll4+/− vessels showed increased expression of VEGF receptor 2 and decreased expression of VEGF receptor 1 compared with wild-type, suggesting they could be more responsive to VEGF stimulation. In addition, expression of dll4 in wild-type tip cells was itself decreased when VEGF signaling was blocked, indicating that dll4 may act downstream of VEGF as a “brake” on VEGF-mediated angiogenic sprouting. Taken together, these data reveal Dll4 as a negative regulator of vascular sprouting and vessel branching that is required for normal vascular network formation during development.
Mechanical and electrical evaluation for the long-term stability of implanted 3D retinal microelectrode

In this paper, the mechanical and electrical characteristics of 3D microelectrode are presented to provide the long-term stability of the implanted microelectrode. As the dimensions of the microelectrode become smaller, the microelectrode can be easily damaged by mechanical pressure and over-injected electric charge. In order to avoid these destructions, allowable mechanical and electrical stress should be determined. Experiments for durability evaluation are set up and performed to measure the mechanical force and safe charge injection limit. The result of the experiments shows that the allowable mechanical force in vertical and horizontal direction is 0.8165 N and 0.2068 N, respectively. In the charge injection test, it is observed that the density of injected charge is a prior factor in microelectrode dissolution rather than the total amount of injected charge.
A Review of the Pharmacological and Biological Activities of the Aerial Parts of Telfairia occidentalis Hook.f. (Cucurbitaceae)

Telfairia occidentalis Hook.f. (Cucurbitaceae) is cultivated in West Africa. The purpose of this article is to review information available in scientific literature on the pharmacological and biological activities of the plant. Searches were made and relevant information obtained from online resources such as Google Scholar, PubMed and Medline. Only literature highlighting the pharmacological, biological and biochemical activities of the plant were selected for this review. The antioxidant, antidiabetic, hepatoprotective, haematological, antiplasmodial, antimicrobial, testiculoprotective, anticancer, antiinflammatory, anxiolytic, sedative and anticonvulsant properties of the plant are documented in this paper. Some of these properties are attributable to the high antioxidant activity of the plant. The medicinal value of Telfairia occidentalis is no longer in doubt. It is expected that this review will be useful to researchers, herbal medical practitioners and agriculturists, and would also enhance optimum exploitation of the plants for its several benefits
Signaling by ROS drives inflammasome activation

Inflammasomes are innate immune signaling pathways that sense pathogens and injury to direct the proteolytic maturation of inflammatory cytokines such as IL‐1β and IL‐18. Among inflammasomes, the NLRP3/NALP3 inflammasome is the most studied. However, little is known on the molecular mechanisms that mediate its assembly and activation. Recent findings suggest that ROS are produced by NLRP3/NALP3 activators and are essential secondary messengers signaling NLRP3/NALP3 inflammasome activation.
A Geobacter sulfurreducens Strain Expressing Pseudomonas aeruginosa Type IV Pili Localizes OmcS on Pili but Is Deficient in Fe(III) Oxide Reduction and Current Production

ABSTRACT The conductive pili of Geobacter species play an important role in electron transfer to Fe(III) oxides, in long-range electron transport through current-producing biofilms, and in direct interspecies electron transfer. Although multiple lines of evidence have indicated that the pili of Geobacter sulfurreducens have a metal-like conductivity, independent of the presence of c-type cytochromes, this claim is still controversial. In order to further investigate this phenomenon, a strain of G. sulfurreducens, designated strain PA, was constructed in which the gene for the native PilA, the structural pilin protein, was replaced with the PilA gene of Pseudomonas aeruginosa PAO1. Strain PA expressed and properly assembled P. aeruginosa PilA subunits into pili and exhibited a profile of outer surface c-type cytochromes similar to that of a control strain expressing the G. sulfurreducens PilA. Surprisingly, the strain PA pili were decorated with the c-type cytochrome OmcS in a manner similar to the control strain. However, the strain PA pili were 14-fold less conductive than the pili of the control strain, and strain PA was severely impaired in Fe(III) oxide reduction and current production. These results demonstrate that the presence of OmcS on pili is not sufficient to confer conductivity to pili and suggest that there are unique structural features of the G. sulfurreducens PilA that are necessary for conductivity.
Synthesis of Aminoquinoline‐Based Aminoalcohols and Oxazolidinones and Their Antiplasmodial Activity

Novel aminoquinoline β‐aminoalcohol and oxazolidinone derivatives were designed, synthesized, and evaluated for in vitro antiplasmodial activity against a chloroquine‐sensitive (3D7) and chloroquine‐resistant (K1) strains of Plasmodium falciparum. A few β‐aminoalcohol derivatives were more potent than chloroquine against chloroquine‐sensetive Plasmodiums. The potency of these derivatives decreased against chloroquine‐resistant species in all cases (higher resistance indices), suggesting a possible cross‐resistance between this group of compounds and chloroquine which could be due to their structural similarity. Although changing β‐aminoalcohols to their oxazolidinone counterparts decreased the potency in all the cases, the compounds were still active and the resistance indices for these compounds improved significantly in comparison with those of β‐aminoalcohols. This may indicate the absence of cross‐resistance between these new derivatives and chloroquine.
Regulation Of Bovine Activated Protein C By Protein S: The Role Of The Cofactor Protein In Species Specificity

The anticoagulant activity of activated Protein C has been observed to be species specific. This could be due either to the inability of the bovine enzyme to recognize its substrate, Factor Va, in non-bovine plasmas, or the absence of cofactor-Protein S, a protein that has been shown to be necessary for the maximum expression of the anticoagulant activity of activated Protein C. Activated Protein C was found to be an effective inhibitor of Factor Xa-initiated clotting of bovine plasma, but without activity in either human or rabbit plasma. Human and rabbit plasma supplemented with bovine Protein S was sensitive to the anticoagulant activity of activated Protein C. Neither rabbit nor human plasma contained bovine activated Protein C cofactor activity as measured by the enhancement of bovine activated Protein C-catalyzed inactivation of Factor Va. However, bovine activated Protein C was able to inactivate both human and rabbit Factor Va. The inactivation of both of these proteins could be stimulated by the addition of bovine Protein S. These results indicate that the species specificity of bovine activated Protein C is due to the absence of a cofactor protein in non-bovine plasma that will interact with the bovine enzyme. Secondly, these findings further confirm that Protein S is required for the maximal expression of the anticoagulant activity of activated Protein C.
Elevated Tissue Factor and Tissue Factor Pathway Inhibitor Circulating Levels in Ischaemic Heart Disease Patients

Summary Several studies have shown that thrombosis and inflammation play an important role in the pathogenesis of Ischaemic Heart Disease (IHD). In particular, Tissue Factor (TF) is responsible for the thrombogenicity of the atherosclerotic plaque and plays a key role in triggering thrombin generation. The aim of this study was to evaluate the TF/Tissue Factor Pathway Inhibitor (TFPI) system in patients with IHD. We have studied 55 patients with IHD and not on heparin [18 with unstable angina (UA), 24 with effort angina (EA) and 13 with previous myocardial infarction (MI)] and 48 sex- and age-matched healthy volunteers, by measuring plasma levels of TF, TFPI, Prothrombin Fragment 1-2 (F1+2), and Thrombin Antithrombin Complexes (TAT). TF plasma levels in IHD patients (median 215.4 pg/ml; range 72.6 to 834.3 pg/ml) were significantly (p<0.001) higher than those found in control subjects (median 142.5 pg/ml; range 28.0-255.3 pg/ml). Similarly, TFPI plasma levels in IHD patients were significantly higher (median 129.0 ng/ml; range 30.3-316.8 ng/ml; p <0.001) than those found in control subjects (median 60.4 ng/ml; range 20.8-151.3 ng/ml). UA patients showed higher amounts of TF and TFPI plasma levels (TF median 255.6 pg/ml; range 148.8-834.3 pg/ml; TFPI median 137.7 ng/ml; range 38.3-316.8 ng/ml) than patients with EA (TF median 182.0 pg/ml; range 72.6-380.0 pg/ml; TFPI median 115.2 ng/ml; range 47.0-196.8 ng/ml) and MI (TF median 213.9 pg/ml; range 125.0 to 341.9 pg/ml; TFPI median 130.5 ng/ml; range 94.0-207.8 ng/ml). Similar levels of TF and TFPI were found in patients with mono- or bivasal coronary lesions. A positive correlation was observed between TF and TFPI plasma levels (r = 0.57, p <0.001). Excess thrombin formation in patients with IHD was documented by TAT (median 5.2 μg/l; range 1.7-21.0 μg/l) and F1+2 levels (median 1.4 nmol/l; range 0.6 to 6.2 nmol/l) both significantly higher (p <0.001) than those found in control subjects (TAT median 2.3 μg/l; range 1.4-4.2 μg/l; F1+2 median 0.7 nmol/l; range 0.3-1.3 nmol/l). As in other conditions associated with cell-mediated clotting activation (cancer and DIC), also in IHD high levels of circulating TF are present. Endothelial cells and monocytes are the possible common source of TF and TFPI. The blood clotting activation observed in these patients may be related to elevated TF circulating levels not sufficiently inhibited by the elevated TFPI plasma levels present.
Natural Diterpenoid Compound Elevates Expression of Bim Protein, Which Interacts with Antiapoptotic Protein Bcl-2, Converting It to Proapoptotic Bax-like Molecule*

Background: Bcl-2-related proteins regulate mitochondrial membrane permeabilization during apoptosis. Results: A natural compound increases Bim/Bcl-2 interaction, permeabilizing the membrane independently of Bax and Bak. Conclusion: Bim converts Bcl-2 to a Bax- or Bak-like molecule. Significance: We revealed a novel apoptotic mechanism that can be explored for developing therapeutics to treat cancers in which dysregulation of Bcl-2 family proteins is common. Overwhelming evidence indicates that Bax and Bak are indispensable for mediating cytochrome c release from mitochondria during apoptosis. Here we report a Bax/Bak-independent mechanism of cytochrome c release and apoptosis. We identified a natural diterpenoid compound that induced apoptosis in bax/bak double knock-out murine embryonic fibroblasts and substantially reduced the tumor growth from these cells implanted in mice. Treatment with the compound significantly increased expression of Bim, which migrated to mitochondria, altering the conformation of and forming oligomers with resident Bcl-2 to induce cytochrome c release and caspase activation. Importantly, purified Bim and Bcl-2 proteins cooperated to permeabilize a model mitochondrial outer membrane; this was accompanied by oligomerization of these proteins and deep embedding of Bcl-2 in the membrane. Therefore, the diterpenoid compound induces a structural and functional conversion of Bcl-2 through Bim to permeabilize the mitochondrial outer membrane, thereby inducing apoptosis independently of Bax and Bak. Because Bcl-2 family proteins play important roles in cancer development and relapse, this novel cell death mechanism can be explored for developing more effective anticancer therapeutics.
The Design and Test of a Digital Relay for Transformer Protection

The inrush current-detection algorithm for the protection of transformers presented in [3] was coupled with a differential overcurrent algorithm and implemented on a popular eight-bit microcomputer system. Multiplication and division was avoided, enabling the use of relatively low-cost processing hardware. A hardware model centered around a transformer generated current data for the data acquisition system. This system translated the time-continuous analog data into the time-discrete digital input data for the algorithms resident in the microcomputer. The algorithms, operating in real time, provided outputs correctly, indicating the presence of either inrush, fault, or low differential current conditions.