Miracle-dz/UniFAR-FTUs huggingface dataset:
Effect of Immunostimulator Baypamun® on Plasma Cortisol Concentration in Gilts Regrouped During theLate Stage of Pregnancy

Baypamun(R) (BPM) preparation (Bayer, Germany) is a virus-based immunostimulator, proved to diminish stress consequences by stimulating immunity and thus compensating/decreasing the immunosuppressive effect of endogenous cortisol. The aim of these investigations was to check whether or not the treatment of gilts with BPM before their transfer from the prefarrowing to farrowing house could indirectly prevent an increase of plasma cortisol by inducing non-specific immunity. The study comprised 40 one-year-old gilts of Swedish Landrace breed in late phase of pregnancy assigned into four groups of 10 animals each. Group I was sampled before transfer (Day 0) and served as a negative control. A positive control (Group 2) was transferred (at Day 0) to the farrowing unit, and then, blood samples were taken at D 1, 3 and 5 following the transfer. Groups 3 and 4 were treated intramuscularly (i.m.) with 2 ml of BPM at D 3 and 1, or 7 and 5, respectively, prior to the transfer, and sampled the same d as Group 2. Significantly lower levels of cortisol (P < 0.05) were recorded at D 3 (after the transfer) in the gilts from Groups 3 and 4, compared to the values obtained for the gilts from Group 2. Moreover, the preparation compensated for severe increase of cortisol in the gilts from Group 3 at D I immediately after the transfer. Accordingly, BPM could be recommended for the prophylactic use as anti-stress preparation for the exposure of swine to the acute stress due to regrouping.
Using Sentence Plausibility to Learn the Semantics of Transitive Verbs

The functional approach to compositional distributional semantics considers transitive verbs to be linear maps that transform the distributional vectors representing nouns into a vector representing a sentence. We conduct an initial investigation that uses a matrix consisting of the parameters of a logistic regression classifier trained on a plausibility task as a transitive verb function. We compare our method to a commonly used corpus-based method for constructing a verb matrix and find that the plausibility training may be more effective for disambiguation tasks.
TGF-β-Dependent Growth Arrest and Cell Migration in Benign and Malignant Breast Epithelial Cells Are Antagonistically Controlled by Rac1 and Rac1b

Despite improvements in diagnosis and treatment, breast cancer is still the most common cancer type among non-smoking females. TGF-β can inhibit breast cancer development by inducing cell cycle arrest in both, cancer cells and, as part of a senescence program in normal human mammary epithelial cells (HMEC). Moreover, TGF-β also drives cell migration and invasion, in part through the small GTPases Rac1 and Rac1b. Depletion of Rac1b or Rac1 and Rac1b in MDA-MB-231 or MDA-MB-435s breast cancer cells by RNA interference enhanced or suppressed, respectively, TGF-β1-induced migration/invasion. Rac1b depletion in MDA-MB-231 cells also increased TGF-β-induced p21WAF1 expression and ERK1/2 phosphorylation. Senescent HMEC (P15/P16), when compared to their non-senescent counterparts (P11/P12), presented with dramatically increased migratory activity. These effects were paralleled by elevated expression of genes associated with TGF-β signaling and metastasis, downregulated Rac1b, and upregulated Rac1. Our data suggest that acquisition of a motile phenotype in HMEC resulted from enhanced autocrine TGF-β signaling, invasion/metastasis-associated gene expression, and a shift in the ratio of antimigratory Rac1b to promigratory Rac1. We conclude that although enhanced TGF-β signaling is considered antioncogenic in HMEC by suppressing oncogene-induced transformation, this occurs at the expense of a higher migration and invasion potential.
Agonists of toll-like receptor (TLR)2 and TLR4 are unable to modulate platelet activation by adenosine diphosphate and platelet activating factor

Summary Inappropriate platelet activation is a feature of acute and chronic diseases such as disseminated intravascular coagulation (DIC) and atherosclerosis. Since proinflammatory microbial-derived agonists can be involved in the pathogenesis of these diseases, we examined the potential role ofTLR4 (mediating responses to LPS) andTLR2 (which responds to bacterial lipopeptides) in platelet activation. Our data suggested low-level expression of TLR2 andTLR4 on platelets, determined by flow cytometry, and we also observed expression of TLR4 on a megakaryocytic cell line by both flow cytometry and immunohistochemistry. Stimulation of the platelets with the TLR4 agonist LPS, and the synthetic TLR2 agonist Pam3CSK4, resulted in no platelet aggregation, no increase in CD62P surface expression and no increase in the cytosolic concentration of Ca2+. The TLR agonists were also unable to directly activate platelets primed with epinephrine, or pretreated with a low concentration ofADP or PAF. Pretreatment of platelets with LPS or Pam3CSK4 also failed to modulate the platelet response to submaximal concentrations of the classical platelet agonists ADP and PAF. We conclude that theTLR agonists LPS and Pam3CSK4 have no direct effect on platelet activation and that platelet TLRs may be a remnant from megakaryocytes. TLR2 and TLR4 agonists are thought to have a significant role in diseases such as atherosclerosis and DIC, but our research suggests that this is through a mechanism other than direct platelet activation or by modification of platelet responses to other agonists.
Risk Aversion and Social Networks

Abstract This paper first investigates empirically the relationship between risk aversion and social network structure in a large group of undergraduate students. We find that risk aversion is strongly correlated to local network clustering, that is, the probability that one has a social tie to friends of friends. We then propose a network formation model that generates this empirical finding, suggesting that locally superior information on benefits makes it more attractive for risk averse individuals to link to friends of friends. Finally, we discuss implications of this model. The model generates a positive correlation between local network clustering and benefits, even if benefits are distributed independently ex ante. This provides an alternative explanation of this relationship to the one given by the social capital literature. We also establish a linkage between the uncertainty of the environment and the network structure: risky environments generate more clustered and more unequal networks in terms of connectivity.
Adult-onset obesity is triggered by impaired mitochondrial gene expression

Reduction in an RNA binding protein impairs mitochondrial biogenesis and alters cell signaling, resulting in obesity. Mitochondrial gene expression is essential for energy production; however, an understanding of how it can influence physiology and metabolism is lacking. Several proteins from the pentatricopeptide repeat (PPR) family are essential for the regulation of mitochondrial gene expression, but the functions of the remaining members of this family are poorly understood. We created knockout mice to investigate the role of the PPR domain 1 (PTCD1) protein and show that loss of PTCD1 is embryonic lethal, whereas haploinsufficient, heterozygous mice develop age-induced obesity. The molecular defects and metabolic consequences of mitochondrial protein haploinsufficiency in vivo have not been investigated previously. We show that PTCD1 haploinsufficiency results in increased RNA metabolism, in response to decreased protein synthesis and impaired RNA processing that affect the biogenesis of the respiratory chain, causing mild uncoupling and changes in mitochondrial morphology. We demonstrate that with age, these effects lead to adult-onset obesity that results in liver steatosis and cardiac hypertrophy in response to tissue-specific differential regulation of the mammalian target of rapamycin pathways. Our findings indicate that changes in mitochondrial gene expression have long-term consequences on energy metabolism, providing evidence that haploinsufficiency of PTCD1 can be a major predisposing factor for the development of metabolic syndrome.
Tumor diversity and evolution revealed through RADseq

Summary Cancer is an evolutionary disease, and there is increasing interest in applying tools from evolutionary biology to understand cancer progression. Restriction-site associated DNA sequencing (RADseq) was developed for the field of evolutionary genetics to study adaptation and identify evolutionary relationships among populations. Here we apply RADseq to study tumor evolution, which allows for unbiased sampling of any desired frequency of the genome, overcoming the selection bias and cost limitations inherent to exome or whole-genome sequencing. We apply RADseq to both human pancreatic cancer and zebrafish melanoma samples. Using either a low-frequency (SbfI, 0.4% of the genome) or high-frequency (NsiI, 6-9% of the genome) cutter, we successfully identify single nucleotide substitutions and copy number alterations in tumors, which can be augmented by performing RADseq on sublineages within the tumor. We are able to infer phylogenetic relationships between primary tumors and metastases. These same methods can be used to identify somatic mosaicism in seemingly normal, non-cancerous tissues. Evolutionary studies of cancer that focus on rates of tumor evolution and evolutionary relationships among tumor lineages will benefit from the flexibility and efficiency of restriction-site associated DNA sequencing.
Feeding by protists and copepods on the heterotrophic dinoflagellates Pfiesteria piscicida, Stoeckeria algicida, and Luciella masanensis

To investigate interactions between the heterotrophic dinoflagellates Pfiesteria pisci- cida, Stoeckeria algicida, and Luciella masanensis and their protozoan and metazoan predators, we measured the growth and/or ingestion rates of the heterotrophic dinoflagellate Oxyrrhis marina, the ciliate Strombidinopsis jeokjo, and the calanoid copepods Acartia spp. (A. hongi and A. omorii) when fed on P. piscicida, S. algicida, and L. masanensis. The maximum growth and ingestion rates of O. marina fed on P. piscicida (0.66 d -1 and 0.33 ng C predator -1 d -1 , respectively) were markedly higher than those of the same predator fed on S. algicida (0.22 d -1 and 0.14 ng C predator -1 d -1 , respectively) or L. masanensis (0.04 d -1 and 0.07 ng C predator -1 d -1 , respectively). The maximum growth and ingestion rates of S. jeokjo fed on P. piscicida and S. algicida (1.61 to 1.77 d -1 and 44 to 49 ng C preda- tor -1 d -1 , respectively) were much higher than when fed on L. masanensis (-0.1 d -1 and 10 ng C predator -1 d -1 , respectively). S. jeokjo had significantly higher attack ratios (number of attempted captures relative to number of physical contacts between predator and prey) when fed on P. piscicida and S. algicida (18 to 25%) than on L. masanensis (5%). Similarly, successful capture (number of prey ingested relative to number of attempted captures) of P. piscicida and S. algicida (82 to 87%) was sig- nificantly higher than that of L. masanensis (2%). L. masanensis may have defensive behavior or chemical protection against predation. However, maximum ingestion rates of Acartia spp. fed on these dinoflagellate species were similar. In understanding the population dynamics and predator- prey interactions of these 3 closely related dinoflagellate species, it is important to distinguish between predation by protists and by copepods.
Cranial anatomy of tyrannosaurid dinosaurs from the Late Cretaceous of Alberta, Canada

Beautifully preserved, nearly complete theropod skeletons from Alberta (Canada) allow re−evaluation of the taxonomic status of North American tyrannosaurids. It is concluded that the most parsimonious interpretation of relationships leads to the separation of the two species of Albertosaurus (sensu Russell 1970) into Gorgosaurus libratus from the Campanian Dinosaur Park Formation and Albertosaurus sarcophagus from the upper Campanian/lower Maastrichtian Horseshoe Canyon Formation. Albertosaurus and Gorgosaurus are closely related, but can be distinguished from each other by more characters than are known to justify generic distinction within another tyrannosaurid clade that includes Daspletosaurus, Tarbosaurus and Tyrannosaurus. Daspletosaurus is known from multiple species that cover extensive geographic, eco− logical and temporal ranges, and it is sensible to maintain its generic distinction from Tyrannosaurus. All tyrannosaurid species have consistent ontogenetic trends. However, one needs to be cautious in assessing ontogenetic stage because many characters are size−dependent rather than age−dependent. There are relatively few osteological differences that can distinguish tyrannosaurid species at any age. For example, Nanotyrannus lancensis is probably a distinct species from Tyrannosaurus rex because there is no evidence of ontogenetic reduction of tooth counts in any other tyrannosaurid spe− cies. Some characters that are good for separating mature tyrannosaurids, such as differences in the sizes and shapes of maxillary fenestrae, are not useful for identifying the species of juveniles.
Towards Interaction Around Unmodified Camera-equipped Mobile Devices

Around-device interaction promises to extend the input space of mobile and wearable devices beyond the common but restricted touchscreen. So far, most around-device interaction approaches rely on instrumenting the device or the environment with additional sensors. We believe, that the full potential of ordinary cameras, specifically user-facing cameras, which are integrated in most mobile devices today, are not used to their full potential, yet. We To this end, we present a novel approach for extending the input space around unmodified mobile devices using built-in front-facing cameras of unmodified handheld devices. Our approach estimates hand poses and gestures through reflections in sunglasses, ski goggles or visors. Thereby, GlassHands creates an enlarged input space, rivaling input reach on large touch displays. We discuss the idea, its limitations and future work.
Emerging roles of mitochondria and autophagy in liver injury during sepsis

Recent research indicates crucial roles of autophagy during sepsis. In animal models of sepsis induced by cecal ligation and puncture (CLP) or the systemic administration of lipopolysaccharides (LPS), autophagy is implicated in the activation and/or damage of various cells/organs, such as immune cells, heart, lung, kidney, and liver. Since sepsis is associated with an increased production of pro- as well as anti-inflammatory cytokines, it has long been considered that hypercytokinemia is a fetal immune response leading to multiple organ failure (MOF) and mortality of humans during sepsis. However, a recent paradigm illuminates the crucial roles of mitochondrial dysfunction as well as the perturbation of autophagy in the pathogenesis of sepsis. In the livers of animal models of sepsis, autophagy is involved in the elimination of damaged mitochondria to prevent the generation of mitochondrial ROS and the initiation of the mitochondrial apoptotic pathway. In addition, many reports now indicate that the role of autophagy is not restricted to the elimination of hazardous malfunctioning mitochondria within the cells; autophagy has been shown to be involved in the regulation of inflammasome activation and the release of cytokines as well as other inflammatory substances. In this review, we summarize recent literature describing the versatile role of autophagy and its possible implications in the pathogenesis of sepsis in the liver.
The Extracellular Loop 2 (ECL2) of the Human Histamine H4 Receptor Substantially Contributes to Ligand Binding and Constitutive Activity

In contrast to the corresponding mouse and rat orthologs, the human histamine H4 receptor (hH4R) shows extraordinarily high constitutive activity. In the extracellular loop (ECL), replacement of F169 by V as in the mouse H4R significantly reduced constitutive activity. Stabilization of the inactive state was even more pronounced for a double mutant, in which, in addition to F169V, S179 in the ligand binding site was replaced by M. To study the role of the FF motif in ECL2, we generated the hH4R-F168A mutant. The receptor was co-expressed in Sf9 insect cells with the G-protein subunits Gαi2 and Gβ1γ2, and the membranes were studied in [3H]histamine binding and functional [35S]GTPγS assays. The potency of various ligands at the hH4R-F168A mutant decreased compared to the wild-type hH4R, for example by 30- and more than 100-fold in case of the H4R agonist UR-PI376 and histamine, respectively. The high constitutive activity of the hH4R was completely lost in the hH4R-F168A mutant, as reflected by neutral antagonism of thioperamide, a full inverse agonist at the wild-type hH4R. By analogy, JNJ7777120 was a partial inverse agonist at the hH4R, but a partial agonist at the hH4R-F168A mutant, again demonstrating the decrease in constitutive activity due to F168A mutation. Thus, F168 was proven to play a key role not only in ligand binding and potency, but also in the high constitutive activity of the hH4R.
Nutritional supplement use among university athletes in Singapore.

INTRODUCTION Nutritional supplements used by athletes can be classified as sports food, dietary supplements and ergogenic aids. The aim of this study was to examine the use of such supplements among university athletes in Singapore. METHODS 82 athletes from 16 sport disciplines completed a questionnaire which sought information on demographical parameters, type of supplements, frequency of use, motivations, knowledge, expenditure and side effects. RESULTS The prevalence of supplement use was 76.8 percent and 20 different products were used. Each individual consumed a mean and standard deviation of 3.18 +/- 1.7 products over a 12-month period. The mean number of products consumed daily was 2.1 +/- 1.2. Popular products included sports drinks, vitamin C, multivitamins and traditional/herbal preparations such as essence of chicken, bird's nest and ginseng. Before using a product, 65.9 percent sought information, usually from the media, the Internet, coaches and fellow athletes. However, many did not know where to obtain reliable information and 86.4 percent were also unaware that supplementation can have adverse effects. CONCLUSION Although there is a high prevalence of supplement use in our study population, many do not have accurate information about these products. Hence, there is an urgent need to provide athletes with education and access to scientific and unbiased information.
High-Throughput Protein Engineering Improves the Antigenicity and Stability of Soluble HIV-1 Envelope Glycoprotein SOSIP Trimers

ABSTRACT Soluble envelope glycoprotein (Env) trimers (SOSIP.664 gp140) are attractive HIV-1 vaccine candidates, with structures that mimic the native membrane-bound Env spike (gp160). Since engineering trimers can be limited by the difficulty of rationally predicting beneficial mutations, here we used a more comprehensive mutagenesis approach with the goal of identifying trimer variants with improved antigenic and stability properties. We created 341 cysteine pairs at predicted points of stabilization throughout gp140, 149 proline residue substitutions at every residue of the gp41 ectodomain, and 362 space-filling residue substitutions at every hydrophobic and aromatic residue in gp140. The parental protein target, the clade B strain B41 SOSIP.664 gp140, does not bind the broadly neutralizing antibody PGT151 and so was used here to identify improved variants that also provide insight into the structural basis for Env antigenicity. Each of the 852 mutants was expressed in human cells and screened for antigenicity using four different monoclonal antibodies (MAbs), including PGT151. We identified 29 trimer variants with antigenic improvements derived from each of the three mutagenesis strategies. We selected four variants (Q203F, T538F, I548F, and M629P) for more comprehensive biochemical, structural, and antigenicity analyses. The T538F substitution had the most beneficial effect overall, including restoration of the PGT151 epitope. The improved B41 SOSIP.664 trimer variants identified here may be useful for vaccine and structural studies. IMPORTANCE Soluble Env trimers have become attractive HIV-1 vaccine candidates, but the prototype designs are capable of further improvement through protein engineering. Using a high-throughput screening technology (shotgun mutagenesis) to create and evaluate 852 variants, we were able to identify sequence changes that were beneficial to the antigenicity and stability of soluble trimers based on the clade B B41 env gene. The strategies described here may be useful for identifying a wider range of antigenically and structurally improved soluble trimers based on multiple genotypes for use in programs intended to create a broadly protective HIV-1 vaccine.
Nuclear Insulin-Like Growth Factor Binding Protein-3 As a Biomarker in Triple-Negative Breast Cancer Xenograft Tumors: Effect of Targeted Therapy and Comparison With Chemotherapy

Triple-negative breast cancer (TNBC) typically has a worse outcome than other breast cancer subtypes, in part owing to a lack of approved therapeutic targets or prognostic markers. We have previously described an oncogenic pathway in basal-like TNBC cells, initiated by insulin-like growth factor binding protein-3 (IGFBP-3), in which the epidermal growth factor receptor (EGFR) is transactivated by sphingosine-1-phosphate (S1P) resulting from sphingosine kinase (SphK)-1 activation. Oncogenic IGFBP-3 signaling can be targeted by combination treatment with the S1P receptor modulator and SphK inhibitor, fingolimod, and the EGFR kinase inhibitor, gefitinib (F + G). However, the interaction of this treatment with chemotherapy has not been documented. Since we observed nuclear localization of IGFBP-3 in some TNBC tumors, this study aimed to evaluate the prognostic significance of nuclear IGFBP-3 in pre-clinical models of basal-like TNBC treated with F + G and doxorubicin. Orthotopic xenograft tumors were grown in nude mice from the human basal-like TNBC cell lines MDA-MB-468 and HCC1806, and were treated with gefitinib, 25 mg/Kg, plus fingolimod, 5 mg/Kg, 3-times weekly. In some studies, doxorubicin was also administered once weekly for 6 weeks. Tumor tissue proteins were quantitated by immunohistochemistry (IHC). Interaction between doxorubicin and F + G was also studied in proliferation assays in vitro. In both tumor models, tissue staining for IGFBP-3 was predominantly nuclear. Combination of F + G significantly enhanced mouse survival, decreased nuclear IGFBP-3 and Ki67 staining, and increased apoptosis (cleaved caspase-3) staining. Kaplan–Meier survival analysis showed that a high tumor IGFBP-3 IHC score (>median), like a high Ki67 score, was significantly associated with shorter survival time, whereas a high apoptosis score was associated with prolonged survival. Studied in vitro in both cell lines, low-dose doxorubicin that had little effect alone, strongly enhanced the cytostatic effect of low-dose F + G combination. However, in both in vivo models, doxorubicin at maximum-tolerated dose neither inhibited tumor growth when administered alone, nor enhanced the significant inhibitory effect of F + G. We conclude that doxorubicin may not add benefit to the inhibitory effect of F + G unless its dose-limiting toxicity can be overcome. Nuclear IGFBP-3 appears to have potential as a prognostic marker in TNBC and could be evaluated for clinical utility.