Miracle-dz/UniFAR-FTUs huggingface dataset:
Identification of Epstein-Barr virus-specific CD8+ T lymphocytes in the circulation of pediatric transplant recipients1

Background. Pediatric transplant recipients are at increased risk for Epstein Barr virus (EBV)-related B cell lymphomas. In healthy individuals, the expansion of EBV-infected B cells is controlled by CD8+ cytotoxic T cells. However, immunosuppressive therapy may compromise antiviral immunity. We identified and determined the frequency of EBV-specific T cells in the peripheral blood of pediatric transplant recipients. Methods. HLA-B*0801 and HLA-A*0201 tetramers folded with immunodominant EBV peptides were used to detect EBV-specific CD8+ T cells by flow cytometry in peripheral blood mononuclear cells from 24 pediatric liver and kidney transplant recipients. The expression of CD38 and CD45RO on EBV-specific, tetramer-binding cells was also examined in a subset of patients by immunofluorescent staining and flow cytometry. Results. Tetramer-binding CD8+ T cells were identified in 21 of 24 transplant recipients. EBV-specific CD8+ T cells were detected as early as 4 weeks after transplant in EBV seronegative patients receiving an organ from an EBV seropositive donor. The frequencies (expressed as a percentage of the CD8+ T cells) of the tetramer-binding cells were HLA-B8-RAKFKQLL (BZLF1 lytic antigen peptide) tetramer, range=0.96 to 3.94%; HLA-B8-FLRGRAYGL (EBNA3A latent antigen peptide) tetramer, range=0.03 to 0.59%; and HLA-A2-GLCTLVAML (BMLF1 lytic antigen peptide) tetramer, range=0.06 to 0.76%. The majority of tetramer reactive cells displayed an activated/memory phenotype. Conclusions. Pediatric transplant recipients receiving immunosuppression can generate EBV-specific CD8+ T cells. Phenotypic and functional analysis of tetramer+ cells may prove useful in defining and monitoring EBV infection in the posttransplant patient.
THE EFFECT OF COBALT CHLORIDE PRECONDITIONING ON PACLITAXEL-INDUCED PERIPHERAL NEUROPATHY.

INTRODUCTION Recent studies indicate that Cobalt Chloride (CoC12) modulates mitochondrial activity. There is emerging data suggesting that Paclitaxel-induced peripheral neuropathy (PIPN) is a consequence of the drug's mitochondrial toxicity. AIM to assess the effect of CoC12 preconditioning on PIPN in an animal model. MATERIAL AND METHOD PIPN was induced by 7 daily consecutive i.p. Paclitaxel (PXT) administrations. Male BALB/c mice were divided into three groups as follows: group A--CoC12 (12.5 mg/kg b.w.) for three weeks (preconditioning) followed by I week of PXT, group B--saline for three weeks, followed by 1 week of PXT and group C--saline for four weeks. Thermal and mechanical allodynia were assessed by means of paw withdrawal latency (PWL). RESULTS In group A, CoC12 preconditioning lead to a decrease in both thermal and mechanical PWLs. 7 days after the last dose of PXT, however, values returned to normal in group A and allodynia for both thermal and mechanical stimuli was noted in group B (p < 0.05). CONCLUSIONS CoC12 preconditioning seems to protect against PIPN. Although CoC12 administration decreased thermal and mechanical PWLs, subsequent P administration did not lead to the persistent mechanical and thermal allodynia that was noted in the P-alone group. Further studies are required for determining the exact relationship between CoC12 and PIPN.
Atypical antipsychotics in the treatment of early-onset schizophrenia

Atypical antipsychotics (AAPs) have been successfully used in early-onset schizophrenia (EOS). This review summarizes the randomized, double-blind, controlled studies of AAPs in EOS, including clozapine, risperidone, olanzapine, aripiprazole, paliperidone, quetiapine, and ziprasidone. No significant differences in efficacy between AAPs were found, with the exception of clozapine and ziprasidone. Clozapine demonstrated superior efficacy in treatment-resistant patients with EOS, whereas ziprasidone failed to demonstrate efficacy in the treatment of EOS. Our review also focuses on the onset of action and weight gain associated with AAPs. The data on onset of action of AAPs in pediatric psychiatry are scanty and inconsistent. Olanzapine appears to cause the most significant weight gain in patients with EOS, while ziprasidone and aripiprazole seem to cause the least.
Optimal Spike-Timing-Dependent Plasticity for Precise Action Potential Firing in Supervised Learning

In timing-based neural codes, neurons have to emit action potentials at precise moments in time. We use a supervised learning paradigm to derive a synaptic update rule that optimizes by gradient ascent the likelihood of postsynaptic firing at one or several desired firing times. We find that the optimal strategy of up- and downregulating synaptic efficacies depends on the relative timing between presynaptic spike arrival and desired postsynaptic firing. If the presynaptic spike arrives before the desired postsynaptic spike timing, our optimal learning rule predicts that the synapse should become potentiated. The dependence of the potentiation on spike timing directly reflects the time course of an excitatory postsynaptic potential. However, our approach gives no unique reason for synaptic depression under reversed spike timing. In fact, the presence and amplitude of depression of synaptic efficacies for reversed spike timing depend on how constraints are implemented in the optimization problem. Two different constraints, control of postsynaptic rates and control of temporal locality, are studied. The relation of our results to spike-timing-dependent plasticity and reinforcement learning is discussed.
Semi-supervised learning with the graph Laplacian: the limit of infinite unlabelled data

We study the behavior of the popular Laplacian Regularization method for Semi-Supervised Learning at the regime of a fixed number of labeled points but a large number of unlabeled points. We show that in ℝd, d ≥ 2, the method is actually not well-posed, and as the number of unlabeled points increases the solution degenerates to a noninformative function. We also contrast the method with the Laplacian Eigenvector method, and discuss the "smoothness" assumptions associated with this alternate method.
Evolution of the Luminosity Function, Star Formation Rate, Morphology, and Size of Star-forming Galaxies Selected at Rest-Frame 1500 and 2800 Å

Using the multiwavelength photometric and spectroscopic data covering the Chandra Deep Field South obtained within the Great Observatories Origins Deep Survey, we investigate the rest-frame UV properties of galaxies to z ~ 2.2, including the evolution of the luminosity function, the luminosity density, star formation rate (SFR), and galaxy morphology. We find a significant brightening (~1 mag) in the rest-frame 2800 Å characteristic magnitude (M*) over the redshift range 0.3 ≲ z ≲ 1.7 and no evolution at higher redshifts. The rest-frame 2800 Å luminosity density shows an increase by a factor of ~4 over the redshift range investigated. We estimate the SFR density to z ~ 2.2 from the 1500 and 2800 Å luminosities. When no correction for extinction is made, we find that the SFR derived from the 2800 Å luminosity density is almost a factor of 2 higher than that derived from the 1500 Å luminosities. Attributing this difference to differential dust extinction, we find that E(B - V) = 0.20 results in the same extinction-corrected SFR from both 1500 and 2800 Å luminosities. The extinction-corrected SFR is a factor of ~6.5 (~3.7) higher than the uncorrected SFR derived from 1500 Å (2800 Å) luminosity. We investigate the morphological composition of our sample by fitting Sérsic profiles to the HST ACS galaxy images at a fixed rest-frame wavelength of 2800 Å at 0.5 ≲ z ≲ 2.2. We find that the fraction of apparently bulge-dominated galaxies (Sérsic index n > 2.5) increases from ~10% at z ~ 0.5 to ~30% at z ~ 2.2. At the same time, we note that galaxies get bluer at increasing redshift. This suggests a scenario where an increased fraction of the star formation takes place in bulge-dominated systems at high redshift. This could be evidence that the present-day elliptical galaxies are a result of assembly (i.e., mergers) of galaxies at z ≳ 1. Finally, we find that galaxy size for a luminosity-selected sample evolves as rh ∝ (1 + z)-1.1 between redshifts z = 2.2 and 1.1. This is consistent with previous measurements and suggests a similar evolution over the redshift range 0 ≲ z ≲ 6.
GLUT-1 mediation of rapid glucose transport in dolphin (Tursiops truncatus) red blood cells.

D-Glucose entry into erythrocytes from adult dolphins (Tursiops truncatus) was rapid, showed saturation at high substrate concentrations, and demonstrated a marked stimulation by intracellular D-glucose. Kinetic parameters were estimated from the concentration dependence of initial rates of tracer entry at 6 degrees C: for zero-trans entry, Michaelis constant (K(m)) was 0.78 +/- 0.10 mM and maximal velocity (Vmax) was 300 +/- 9 mumol.l cell water-1.min-1; for equilibrium exchange entry, K(m) was 17.5 +/- 0.6 mM and Vmax was 8,675 +/- 96 mumol.l cell water-1.min-1. Glucose entry was inhibited by cytochalasin B, and mass law analysis of reversible, D-glucose-displaceable, cytochalasin B binding gave values of 0.37 +/- 0.03 nmol/mg membrane protein for maximal binding and 0.48 +/- 0.10 microM for the dissociation constant. Dolphin glucose transporter polypeptides were identified on sodium-dodecyl sulfate-polyacrylamide gel electrophoresis immunoblots [using antibodies that recognized human glucose transporter isoform (GLUT-1)] as two molecular species, apparent relative molecular weights of 53,000 and 47,000. Identity of these polypeptides was confirmed by D-glucose-sensitive photolabeling of membranes with [3H]cytochalasin B. Digestion of both dolphin and human red blood cell membranes with glycopeptidase F led to the generation of a sharp band of relative molecular weight 46,000 derived from GLUT-1. Trypsin treatment of human and dolphin erythrocyte membranes generated fragmentation patterns consistent with similar polypeptide structures for GLUT-1 in human and dolphin red blood cells.
Does Zika Virus Cause Microcephaly - Applying the Bradford Hill Viewpoints

Introduction: Zika virus has been documented since 1952, but been associated with mild, self-limiting disease. Zika virus is classified as an arbovirus from a family of Flaviviridae and primarily spread by Aedes Aegypti mosquitos. However, in a large outbreak in Brazil in 2015, Zika virus has been associated with microcephaly. Methods: In this review we applied the Bradford-Hill viewpoints to investigate the association between Zika virus and microcephaly. We examined historical studies, available data and also compared historical rates of microcephaly prior to the Zika virus outbreak. The available evidence was reviewed against the Bradford Hill viewpoints. Results: All the nine criteria were met to varying degrees: strength of association, consistency of the association, specificity, temporality, plausibility, coherence, experimental evidence, biological gradient and analogy. Conclusion: Using the Bradford Hill Viewpoints as an evaluation framework for causation is highly suggestive that the association between Zika virus and microcephaly is causal. Further studies using animal models on the viewpoints which were not as strongly fulfilled would be helpful.
Alteration of the proteostasis network of plant cells promotes the post-endoplasmic reticulum trafficking of recombinant mutant (L444P) human β-glucocerebrosidase

Gaucher disease is a prevalent lysosomal storage disease characterized by a deficiency in the activity of lysosomal acid β-glucosidase (glucocerebrosidase, GCase, EC 3.2.1.45). One of the most prevalent disease-causing mutations in humans is a L444P missense mutation in the GCase protein, which results in its disrupted folding in the endoplasmic reticulum (ER) and impaired post-ER trafficking. To determine whether the post-ER trafficking of this severely malfolded protein can be restored, we expressed the mutant L444P GCase as a recombinant protein in transgenic tobacco (Nicotiana tabacum L. cv Bright Yellow 2 [BY2]) cells, in which the GCase variant was equipped with a plant signal peptide to allow for secretion upon rescued trafficking out of the ER. The recombinant L444P mutant GCase was retained in the plant endoplasmic reticulum (ER). Kifunensine and Eeyarestatin I, both inhibitors of ER-associated degradation (ERAD), and the proteostasis regulators, celastrol and MG-132, increased the steady-state levels of the mutant protein inside the plant cells and further promoted the post-ER trafficking of L444P GCase, as indicated by endoglycosidase-H sensitivity- and secretion- analyses. Transcript profiling of genes encoding ER-molecular chaperones, ER stress responsive proteins, and cytoplasmic heat shock response proteins, revealed insignificant or only very modest changes in response to the ERAD inhibitors and proteostasis regulators. An exception was the marked response to celastrol which reduced the steady-state levels of cytoplasmic HSP90 transcripts and protein. As HSP90 participates in the targeting of misfolded proteins to the proteasome pathway, its down-modulation in response to celastrol may partly account for the mechanism of improved homeostasis of L444P GCase mediated by this triterpene.
Morphogenetic clonal growth of kidney epithelial cell line MDCK

MDCK (Madin‐Darby canine kidney) cells were cultured either (1) dispersed within hydrated collagen gel (HCG) or (2) seeded atop a collagen substrate and then immediately overlaid with HCG. Individual cells exhibited clonal growth in three dimensions to form spherical cysts made up of a simple epithelium enclosing a fluid‐filled lumen. The cells of MDCK cysts were polarized with the basolateral surface in contact with the collagen gel and the apical surface bordering the lumen. The ultrastructure of MDCK cysts showed similarities to distal nephron. The cells bore apical microvilli and solitary cilia and had occluding junctions and a simple basolateral surface. MDCK cysts increased in size (> 800 μm diameter) with continued culture. MDCK cysts grown between layers of HCG were stripped free of the overlying collagen to give direct access to basolateral surface membrane. Unlike monolayer culture, morphogenetic clonal growth of cell line MDCK produces a polarized cell population with a true lumenal and basolateral surface. Collagen‐gel‐cultured MDCK cysts provide an easily manipulable in vitro cell system that may offer unique advantages for the study of renal cell structure and function.
Effects of deletions in the carboxy-terminal hydrophobic region of herpes simplex virus glycoprotein gB on intracellular transport and membrane anchoring

The gB glycoprotein of herpes simplex virus type 1 is involved in viral entry and fusion and contains a predicted membrane-anchoring sequence of 69 hydrophobic amino acids, which can span the membrane three times, near the carboxy terminus. To define the membrane-anchoring sequence and the role of this hydrophobic stretch, we have constructed deletion mutants of gB-1, lacking one, two, or three predicted membrane-spanning segments within the 69 amino acids. Expression of the wild-type and mutant glycoproteins in COS-1 cells show that mutant glycoproteins lacking segment 3 (amino acids 774 to 795 of the gB-1 protein) were secreted from the cells. Protease digestion and alkaline extraction of microsomes containing labeled mutant proteins further showed that segment 3 was sufficient for stable membrane anchoring of the glycoproteins, indicating that this segment may specify the transmembrane domain of the gB glycoprotein. Also, the mutant glycoproteins containing segment 3 were localized in the nuclear envelop, which is the site of virus budding. Deletion of any of the hydrophobic segments, however, affected the intracellular transport and processing of the mutant glycoproteins. The mutant glycoproteins, although localized in the nuclear envelope, failed to complement the gB-null virus (K082). These results suggest that the carboxy-terminal hydrophobic region contains essential structural determinants of the functional gB glycoprotein.
Late Oligocene rodents from Banovići (Bosnia and Herzegovina)

The family Muridae dominates the Banovici (Bosnia and Herzegovina) rodent assemblage in diversity as well as in number of specimens. The glirids are the second in importance and the sciurids are only represented by few specimens. The composition of the assemblage is on species level quite unique and on genus level more similar to assemblages from the Earliest Miocene of Anatolia than to assemblages from the Late Oligocene and Early Miocene of Western Europe. In the latter area the murid genera Deperetomys, Mirrabella and Eumyarion are absent. The species of these genera from Banovici combine primitive and derived features and seem to represent the oldest member of their genus or even family, and do not fit in previously reconstructed evolutionary trends. The evolutionary history of the Spalacinae seems to be much more complex than thought so far. Theridomyidae and Eomyidae, typical for Late Oligocene Western European rodent assemblages, are absent in the Banovici assemblage as well as in the Anatolian ones. The Banovici assemblage is in this aspect also more similar to Anatolian rodent assemblages than to European ones. Newly named species are Bransatoglis bosniensis, Deperetomys magnus, Eumyarion margueritae, and in a new genus, Vetusspalax progressus. This small mammal study was combined with a magnetostratigraphic investigation of the sedimentary infill of the Banovici basin in Bosnia and Herzegovina. The age correlation of the fauna as well as the magnetostratigraphic data indicate an infill of the Banovici basin between 24–22 Ma. The rodent fauna is from the base of the basin infill, just below the major coal seam, and of an age of ~ 24 Ma. K e y w o r d s : Bosnia and Herzegovina, Dinarides, Oligocene, Miocene, rodents, systematics, biostratigraphy, biogeography. PALAEODIVERSITY 6, 2013 64 De leeuw et al. (2011) used the Banovici rodent fauna for correlating the sediments of the Banovici Basin to the GPTS and only briefly discussed the assemblage. In this paper the rodent fauna, with several new species, is described in detail and its biostratigraphic significance and biogeographic implications are discussed. The lagomorphs, insectivores and marsupials will be published in a separate paper.
Effects of progesterone pretreatment on the oxytocin receptor concentration and the response to oxytocin during the simulated early luteal phase in the ovariectomized ewe.

A steroid-treated ovariectomized ewe model was used to investigate the role of progesterone pretreatment in the control of functional oxytocin receptor concentrations during the early luteal phase. Ovariectomized ewes (n = 28) were injected with oestradiol for 2 days (final injection = day 0) with or without progesterone pretreatment (progestagen sponge for 10 days). Ewes were then given high or low concentrations of progesterone combined with high, low or zero concentrations of oestradiol in a pattern known to simulate the early luteal phase profile (n = 4 per group). Ewes were given 1 microgram oxytocin (i.v.) on day 4 and plasma was collected to assay 13,14-dihydro-15-keto PGF2 alpha. The concentration of progesterone and oestradiol administered had no effect on the concentration of 13,14-dihydro-15-keto PGF2 alpha following oxytocin administration (P > 0.05). However, the group that was not pretreated exhibited a small but significant 13,14-dihydro-15-keto PGF2 alpha response in comparison with the equivalent pretreated group (P < 0.05). In a subsequent study, ewes were divided into groups pretreated and not pretreated with progesterone; both groups were given oestrous concentrations of oestradiol and high concentrations of progesterone and oestradiol together. On day 0, 2, 3 or 4, ewes from each group (n = 3, 3, 4 and 4, respectively) were given 1 microgram of oxytocin i.v. , and the endometrium was collected to measure the binding of oxytocin receptors. Oxytocin caused a significant (P < 0.05) increase in the concentration of 13,14-dihydro-15-keto PGF2 alpha in all ewes on day 0 but not on days 2, 3 or 4. Oxytocin receptor concentrations were maximal on day 0 and basal by day 4. (ABSTRACT TRUNCATED AT 250 WORDS)
Hypothyroidism is a Risk Factor for Atrial Fibrillation after Coronary Artery Bypass Graft

Introduction Few reports in the world have shown a differential effect of hypothyroidism in relation to morbidity and mortality following cardiac surgery. Objective To determine the association between preoperative hypothyroidism, composite and disaggregated outcomes of mortality and complications in patients undergoing first-time isolated myocardial revascularization surgery. Methods Historical cohort of patients undergoing myocardial revascularization between January 2008 and December 2014, with 626 patients included for evaluation of the composite and disaggregated outcomes of in-hospital mortality and complications (atrial fibrillation, surgical site infection and reoperation due to bleeding). A logistic regression model was used to determine the association between hypothyroidism and the onset of those outcomes. Results Cohort of 1696 eligible patients for the study, with 1.8 mortality. Median age, female gender and prevalence of arterial hypertension were all significantly higher among hypothyroid patients. No differences were found in other preoperative or intraoperative characteristics. Hypothyroidism was associated with the presence of the composite outcome, RR 1.6 (1.04-2.4) and atrial fibrillation 1.9 (1.05-3.8). No association with mortality, infections or reoperation due to bleeding was found. Conclusion Hypothyroidism is a disease that affects females predominantly and does not determine the presence of other comorbidities. Hypothyroidism is a risk factor for the onset of postoperative fibrillation in patients undergoing myocardial revascularization surgery. Postoperative care protocols focused on the prevention of these complications in this type of patients must be instituted.