Miracle-dz/UniFAR-FTUs huggingface dataset:
ACT3: a putative centractin homologue in S. cerevisiae is required for proper orientation of the mitotic spindle

As part of our ongoing efforts to understand the functional role of vertebrate centractins, we have identified a new member of the actin- related family of proteins in the yeast Saccharomyces cerevisiae using a PCR-based approach. Consistent with the current nomenclature for actin-related proteins in yeast, we propose to denote this locus ACT3. The primary amino acid sequence of Act3p is most similar to canine and human alpha-centractin (73% similarity/54% identity). The sequence of a genomic clone indicates ACT3 lies adjacent to and is transcribed convergently with respect to FUR1 on chromosome VIII. Molecular genetic analysis indicates ACT3 is represented by a single gene from which the corresponding mRNA is expressed at a low level compared to ACT1. Tetrad analysis of heterozygotes harboring a TRP1 replacement of the ACT3- coding region indicates ACT3 is nonessential for growth under normal conditions and at extremes of temperature and osmolarity. However, growth at 14 degrees C indicates a spindle orientation defect similar to phenotypes recently described for yeast harboring mutations in actin, tubulin, or cytoplasmic dynein. Taken together, our data suggest that ACT3 is the S. cerevisiae homologue of vertebrate centractins.
Expression of the Third Intracellular Loop of the δ-Opioid Receptor Inhibits Signaling by Opioid Receptors and Other G Protein-Coupled Receptors

To explore the feasibility of developing inhibitors of signaling by opioid receptors and other G protein-coupled receptors (GPCRs) that use the same G protein pool, we investigated the capacity of a minigene encoding the third intracellular loop of the δ-opioid receptor (δ-i3L) to act as competitive antagonist of the receptor-G protein interface interaction. In δ-i3L-expressing cells, the peptide blocked high-affinity agonist binding to both the δ- and the μ-opioid (δ-OR and μ-OR) and attenuated opioid and α2-adrenergic receptor (α2AR)-dependent [35S]guanosine-5′-O-(3-thio)triphosphate binding. Furthermore, δ-i3L expression resulted in inhibition of δ-, μ-OR-, and α2AR-receptor-mediated cAMP accumulation, whereas the cAMP response produced by activation of the β2-adrenergic receptor was unaffected, suggesting that the inhibitory effects of δ-i3L expression were selective for Gi/Go proteins. Moreover, although δ-i3L expression also attenuated drastically phospholipase C accumulation and Ca2+ release following μ- and δ-OR stimulation, it failed to inhibit carbachol-mediated stimulation of inositol phosphate accumulation in M1-muscarinic receptor-expressing human embryonic kidney 293 cells. Finally, we also examined the effects of δ-i3L expression on the regulation of the extracellular signal-regulated kinase (ERK) mitogen-activated protein kinase pathway. Our results demonstrate that, although ERK activation by μ- and δ-ORs is attenuated by the presence of δ-i3L, ERK activation mediated by α2AR remained unaffected. Collectively, our data demonstrate that the δ-i3L can be used as potent inhibitor of G protein signaling for various GPCRs that use a common pool of G proteins.
The Grad Cohort Workshop: Evaluating an Intervention to Retain Women Graduate Students in Computing

Women engaged in computing career tracks are vastly outnumbered by men and often must contend with negative stereotypes about their innate technical aptitude. Research suggests women's marginalized presence in computing may result in women psychologically disengaging, and ultimately dropping out, perpetuating women's underrepresentation in computing. To combat this vicious cycle, the Computing Research Association's Committee on the Status of Women in Computing Research (CRA-W) runs a multi-day mentorship workshop for women graduate students called Grad Cohort, which consists of a speaker series and networking opportunities. We studied the long-term impact of Grad Cohort on women Ph.D. students' (a) dedication to becoming well-known in one's field, and giving back to the community (professional goals), (b) the degree to which one feels computing is an important element of “who they are” (computing identity), and (c) beliefs that computing skills are innate (entity beliefs). Of note, entity beliefs are known to be demoralizing and can lead to disengagement from academic endeavors. We compared a propensity score matched sample of women and men Ph.D. students in computing programs who had never participated in Grad Cohort to a sample of past Grad Cohort participants. Grad Cohort participants reported interest in becoming well-known in their field to a greater degree than women non-participants, and to an equivalent degree as men. Also, Grad Cohort participants reported stronger interest in giving back to the community than their peers. Further, whereas women non-participants identified with computing to a lesser degree than men and held stronger entity beliefs than men, Grad Cohort participants' computing identity and entity beliefs were equivalent to men. Importantly, stronger entity beliefs predicted a weaker computing identity among students, with the exception of Grad Cohort participants. This latter finding suggests Grad Cohort may shield students' computing identity from the damaging nature of entity beliefs. Together, these findings suggest Grad Cohort may fortify women's commitment to pursuing computing research careers and move the needle toward greater gender diversity in computing.
What Do We Learn from Spheroid Culture Systems? Insights from Tumorspheres Derived from Primary Colon Cancer Tissue

Due to their self-renewal and tumorigenic properties, tumor-initiating cells (TICs) have been hypothesized to be important targets for colorectal cancer (CRC). However the study of TICs is hampered by the fact that the identification and culturing of TICs is still a subject of extensive debate. Floating three-dimensional spheroid cultures (SC) that grow in serum-free medium supplemented with growth factors are supposed to be enriched in TICs. We generated SC from fresh clinical tumor specimens and compared them to SC isolated from CRC cell-lines as well as to adherent differentiated counterparts. Patient-derived SC display self-renewal capacity and can induce serial transplantable tumors in immuno-deficient mice, which phenotypically resemble the tumor of origin. In addition, the original tumor tissue and established SC retain several similar CRC-relevant mutations. Primary SC express key stemness proteins such as SOX2, OCT4, NANOG and LGR5 and importantly show increased chemoresistance ability compared to their adherent differentiated counterparts and to cell line-derived SC. Strikingly, cells derived from spheroid or adherent differentiating culture conditions displayed similar self-renewal capacity and equally formed tumors in immune-deficient mice, suggesting that self-renewal and tumor-initiation capacity of TICs is not restricted to phenotypically immature spheroid cells, which we describe to be highly plastic and able to reacquire stem-cell traits even after long differentiation processes. Finally, we identified two genes among a sphere gene expression signature that predict disease relapse in CRC patients. Here we propose that SC derived from fresh patient tumor tissue present interesting phenotypic features that may have clinical relevance for chemoresistance and disease relapse and therefore represent a valuable tool to test for new CRC-therapies that overcome drug resistance.
Study of the Thiol/Disulfide Redox Systems of the Anaerobe Desulfovibrio vulgaris Points Out Pyruvate:Ferredoxin Oxidoreductase as a New Target for Thioredoxin 1

Sulfate reducers have developed a multifaceted adaptative strategy to survive against oxidative stresses. Along with this oxidative stress response, we recently characterized an elegant reversible disulfide bond-dependent protective mechanism in the pyruvate:ferredoxin oxidoreductase (PFOR) of various Desulfovibrio species. Here, we searched for thiol redox systems involved in this mechanism. Using thiol fluorescent labeling, we show that glutathione is not the major thiol/disulfide balance-controlling compound in four different Desulfovibrio species and that no other plentiful low molecular weight thiol can be detected. Enzymatic analyses of two thioredoxins (Trxs) and three thioredoxin reductases allow us to propose the existence of two independent Trx systems in Desulfovibrio vulgaris Hildenborough (DvH). The TR1/Trx1 system corresponds to the typical bacterial Trx system. We measured a TR1 apparent Km value for Trx1 of 8.9 μm. Moreover, our results showed that activity of TR1 was NADPH-dependent. The second system named TR3/Trx3 corresponds to an unconventional Trx system as TR3 used preferentially NADH (Km for NADPH, 743 μm; Km for NADH, 5.6 μm), and Trx3 was unable to reduce insulin. The Km value of TR3 for Trx3 was 1.12 μm. In vitro experiments demonstrated that the TR1/Trx1 system was the only one able to reactivate the oxygen-protected form of Desulfovibrio africanus PFOR. Moreover, ex vivo pulldown assays using the mutant Trx1C33S as bait allowed us to capture PFOR from the DvH extract. Altogether, these data demonstrate that PFOR is a new target for Trx1, which is probably involved in the protective switch mechanism of the enzyme.
Im2depth: Scalable exemplar based depth transfer

The rapid increase in number of high quality mobile cameras have opened up an array of new problems in mobile vision. Mobile cameras are predominantly monocular and are devoid of any sense of depth, making them heavily reliant on 2D image processing. Understanding 3D structure of scenes being imaged can greatly improve the performance of existing vision/graphics techniques. In this regard, recent availability of large scale RGB-D datasets beg for more effective data driven strategies to leverage the scale of data. We propose a depth recovery mechanism “im2depth”, that is lightweight enough to run on mobile platforms, while leveraging the large scale nature of modern RGB-D datasets. Our key observation is to form a basis (dictionary) over the RGB and depth spaces, and represent depth maps by a sparse linear combination of weights over dictionary elements. Subsequently, a prediction function is estimated between weight vectors in RGB to depth space to recover depth maps from query images. A final superpixel post processor aligns depth maps with occlusion boundaries, creating physically plausible results. We conclude with thorough experimentation with four state of the art depth recovery algorithms, and observe an improvement of over 6.5 percent in shape recovery, and over 10cm reduction in average L1 error.
Ventricular Geometry, Strain, and Rotational Mechanics in Pulmonary Hypertension

Background— We tested the hypothesis that right ventricular (RV) pressure overload affects RV function and further influences left ventricular (LV) geometry, which adversely affects LV twist mechanics and segmental function. Methods and Results— Echocardiographic images were prospectively acquired in 44 patients (age, 46±12 years; 82% women) with evidence of pulmonary hypertension (estimated pulmonary artery systolic pressure, 71±23 mm Hg) and in 44 age- and gender-matched healthy subjects. Patients with intrinsic LV diseases were excluded. RV lateral wall longitudinal strain (LS) and interventricular septal (IVS) LS were reduced in the pulmonary hypertension group compared with control subjects (−15.9±7.6% versus −25.5±6.1%, P<0.001; and −17.3±4.4% versus −20.2±3.9%, P=0.002, respectively), whereas LV lateral wall LS was preserved. RV lateral wall LS and IVS LS, but not LV lateral wall LS, correlated with pulmonary artery systolic pressure (r=0.56, P<0.01; r=0.32, P<0.01) and LV eccentricity index (r=0.57, P<0.01; r=0.57, P<0.01). IVS and LV lateral wall circumferential strain (CS) were both reduced in the pulmonary hypertension group. Although IVS CS and LV lateral wall CS correlated with pulmonary artery systolic pressure and LV eccentricity index, after adjustment of CS for LV eccentricity index, differences between groups persisted for IVS CS (P<0.01) but not LV lateral wall CS (P=0.09). LV torsion was decreased in patients with pulmonary hypertension compared with control subjects (9.6±4.9° versus 14.7±4.9°, P<0.001). LV torsion inversely correlated with pulmonary artery systolic pressure (r=−0.39, P<0.01) and LV eccentricity index (r=−0.3, P<0.01). LV untwisting rates were similar in both groups (P=0.7). Conclusions— Chronic RV pressure overload directly affects RV longitudinal systolic deformation. RV pressure overload further influences IVS and LV geometry, which impairs LV torsion and segmental LS and CS, more for the IVS than for the free wall of the LV.
Does SYNTAX score predict in-hospital outcomes in patients with ST elevation myocardial infarction undergoing primary percutaneous coronary intervention?

BACKGROUND SYNTAX score (SxS) has been demonstrated to predict long-term outcomes in stable patients with coronary artery disease. But its prognostic value for patients with acute coronary syndrome remains unknown. AIM To evaluate whether SxS could predict in-hospital outcomes for patients admitted with ST elevation myocardial infarction (STEMI) who undergo primary percutaneous coronary intervention (pPCI). METHODS The study included 538 patients with STEMI who underwent pPCI between January 2010 and December 2012. The patients were divided into two groups: low SxS (< 22) and high SxS (> 22). The SxS of all patients was calculated from aninitial angiogram and TIMI flow grade of infarct related artery was calculated after pPCI. Left ventricular systolic functions of the patients were evaluated with an echocardiogram in the following week. The rates of reinfarction and mortality during hospitalisation were obtained from the medical records of our hospital. RESULTS The high SxS group had more no-reflow (41% and 25.1%, p < 0.001, respectively), lower ejection fraction (38.2 ± 7.5% and 44.6 ± 8.8%, p < 0.001, respectively), and greater rates of re-infarction (9.5% and 7.3%, p = 0.037, respectively) and mortality (0.9% and 0.2%, p = 0.021, respectively) during hospitalisation compared to the low SxS group. On multivariate logistic regression analysis including clinical variables, SxS was an independent predictor of no-reflow (OR 1.081, 95% CI 1.032-1.133, p = 0.001). CONCLUSIONS SxS is a useful tool that can predict in-hospital outcomes of patients with STEMI undergoing pPCI.
Sexual disorders beyond DSM-5: the unfinished affaire

Purpose of review To provide an overview of post-The Diagnostic and Statistical Manual of Mental Disorders, 5th ed. classifications related to human sexuality. After reviewing the literature on classification and clinical practice of sexual disorders, some of the most important contributions on main sexological classifications and frameworks were selected, especially from January 2016 till June 2017. Recent findings New relevant contributions on psychiatric and sexological classifications and frameworks have been proposed, such as the international classification of diseases 11th revision (ICD-11), research domain criteria, the third edition of the Diagnostic Manual in Sexology and the person-centered psychiatry perspective. Summary ICD-11 proposals regarding conditions related to sexual health including sexual dysfunctions and gender incongruence as well as vaginismus, such as sexual pain disorder, paraphilic disorders as mental Disorders. The disorders associated with sexual development and orientation, are proposed for deletion. The other perspectives aforementioned are also presented.
Bilberries potentially alleviate stress-related retinal gene expression induced by a high-fat diet in mice

Purpose Obesity- and diabetes-associated visual impairment and vascular dysfunctions are increasing as causes of vision loss. The detailed mechanisms of how obesity and diabetes affect eye health are still largely unknown, but animal models have been useful in exploring the effects of potential protective compounds, i.e., compounds characterized by antioxidant and anti-inflammatory properties. These properties occur in anthocyanins, and bilberries (European wild blueberries, Vaccinium myrtillus) are a major source of dietary anthocyanins in Nordic diets. The main aim of the present work was to study the protective effects of dietary bilberries (BB) on the level of gene expression in retinas in mice that develop obesity when fed a high-fat diet (HFD). Methods Mice (n=6 per group, four groups) were fed ad libitum a normal control diet (NCD), a HFD, or a diet with 5% bilberries (NCD+BB, HFD+BB) for 12 weeks. Food consumption, weight gain, and blood pressure were measured during the feeding period and whole blood serum markers of obesity at sacrifice. Retinas were collected, and RNA extracted from all 24 mice and pooled samples from four mice per group were hybridized to Mouse-Ref8 V2 Expression BeadChips (Illumina platform) with 25,697 probes for genes and transcript variants. The expression profiles in the retinas were analyzed using R, PathVisio, and DAVID to screen for high fat–induced changes as well as for bilberry-induced changes in the HFD up- or downregulated transcripts. Results The HFD and HFD+BB groups gained weight from week 5 and final weight, blood glucose, serum free fatty acids, and systolic blood pressure as compared to mice fed the control diets (Mann–Whitney’s U-test, p<0.05). Bilberries had no significant effect on these parameters other than a trend to reduce systolic blood pressure in the HFD-fed mice (101±4 versus 113±9 mmHg, p=0.10). Gene ontology enrichment analysis of 810 differentially expressed genes (F-test, p<0.05) in the retina displayed differential regulation of genes in ontology groups, mainly pathways for apoptosis, inflammation, and oxidative stress, especially systemic lupus erythematosus, mitogen-activated protein kinase, and glutathione metabolism. Mice fed a HFD had increased retinal gene expression of several crystallins, while the HFD+BB mice showed potential downregulation of these crystallins when compared to the HFD mice. Bilberries also reduced the expression of genes in the mitogen-activated protein kinase (MAPK) pathway and increased those in the glutathione metabolism pathway. Conclusions HFD feeding induces differential expression of several stress-related genes in the mouse retina. Despite minor effects in the phenotype, a diet rich in bilberries mitigates the upregulation of crystallins otherwise induced by HFD. Thus, the early stages of obesity-associated and stress-related gene expression changes in the retina may be prevented with bilberries in the diet.
Reduction of porous media permeability from in situ Leuconostoc mesenteroides growth and dextran production

In situ growth of bacteria in a porous medium can alter the permeability of that media. This article reveals that the rate of permeability alteration can be controlled by the inoculation strategy, nutrient concentrations, and injection rates. Based on experimental observations a phenomenological model has been developed to describe the inoculation of the porous medium, the in situ growth of bacteria, and the permeability decline of the porous medium. This model consists of two phases that describe the bacteria in the porous medium: (1) the nongrowth phase in which cell transport and retention are occurring; and (2) the growth phase in which the retained cells grow and plug the porous media. Transition from the transport phase to the growth phase is governed by the growth lag time of the cells within the porous medium. The importance of the inoculum injection strategy and the nutrient injection strategy is illustrated by the model. © 1996 John Wiley & Sons, Inc.
Downregulation of circadian clock genes in chronic myeloid leukemia: Alternative methylation pattern of hPER3

Disruption of circadian rhythm is believed to play a critical role in cancer development. To gain further insights into the roles of circadian genes in chronic myeloid leukemia (CML), we analyzed peripheral blood from 53 healthy individuals and 35 CML patients for the expression of the nine circadian genes. The expression levels of hPER1, hPER2, hPER3, hCRY1, hCRY2 and hBMAL1 were significantly impaired in both chronic phase and blastic crisis of CML cases compared with those in healthy individuals (P < 0.001). Methylation studies in the promoter areas of these six genes revealed that only the CpG sites of the hPER3 gene were methylated in all of the CML patients, and the methylated CpG frequencies differed significantly in patients at blastic crisis (8.24 ± 0.73) or at chronic phase (4.48 ± 0.48). The CpG sites of the hPER2 gene were also methylated in 40% of the CML patients. No mutation was found within the coding region of hPER3 in CML cases. Our results suggest that the downregulated hPER3 expression in CML is correlated with the inactivation of hPER3 by methylation. (Cancer Sci 2006; 97: 1298–1307)
Tween-80 Alters Natural Resistance of Sarcoma-180 to Bouvardin (NSC 259968)

Sarcoma-180 tumour (S-180) exhibits natural resistance to bouvardin (NSC 259968), a protein synthesis inhibitor that also inhibits RNA and DNA synthesis when administered over a range of non-toxic doses using 0.9 % NaCl as a vehicle. However, using Tween-80 as a vehicle, there is a substantial enhancement of cytotoxicity and a subsequent increase in the life span of animals bearing the S-180 tumour. This observation was substantiated in vitro by exposing S-180 cells to 10−6 M bouvardin in the presence and absence of Tween-80. Bouvardin, 10−6 M, in the absence of Tween-80, inhibited the incorporation of [3H]uridine by 46 %, whereas the presence of Tween-80 resulted in a 66 % inhibition of uridine incorporation.
IL‐15 Induces Alloreactive CD28− Memory CD8 T Cell Proliferation and CTLA4‐Ig Resistant Memory CD8 T Cell Activation

The presence of CD28− memory CD8 T cells in the peripheral blood of renal transplant patients is a risk factor for graft rejection and resistance to CTLA‐4Ig induction therapy. In vitro analyses have indicated poor alloantigen‐induced CD28− memory CD8 T cell proliferation, raising questions about mechanisms mediating their clonal expansion in kidney grafts to mediate injury. Candidate proliferative cytokines were tested for synergy with alloantigen in stimulating CD28− memory CD8 T cell proliferation. Addition of IL‐15, but not IL‐2 or IL‐7, to co‐cultures of CD28− or CD28+ memory CD8 T cells and allogeneic B cells rescued proliferation of the CD28− and enhanced CD28+ memory T cell proliferation. Proliferating CD28− memory CD8 T cells produced high amounts of interferon gamma and tumor necrosis factor alpha and expressed higher levels of the cytolytic marker CD107a than CD28+ memory CD8 T cells. CTLA‐4Ig inhibited alloantigen‐induced proliferation of CD28+ memory CD8 T cell proliferation but had no effect on alloantigen plus IL‐15‐induced proliferation of either CD28− or CD28+ memory CD8 T cells. These results indicate the ability of IL‐15, a cytokine produced by renal epithelial during inflammation, to provoke CD28− memory CD8 T cell proliferation and to confer memory CD8 T cell resistance to CTLA‐4Ig‐mediated costimulation blockade.