Miracle-dz/UniFAR-FTUs huggingface dataset:
Recurrent selection with reduced 2,4-D amine doses results in the rapid evolution of 2,4-D herbicide resistance in wild radish (Raphanus raphanistrum L.).

BACKGROUND When used at effective doses, weed resistance to auxinic herbicides has been slow to evolve when compared with other modes of action. Here we report the evolutionary response of a herbicide-susceptible population of wild radish (Raphanus raphanistrum L.) and confirm that sublethal doses of 2,4-dichlorophenoxyacetic acid (2,4-D) amine can lead to the rapid evolution of 2,4-D resistance and cross-resistance to acetolactate synthase (ALS)-inhibiting herbicides. RESULTS Following four generations of 2,4-D selection, the progeny of a herbicide-susceptible wild radish population evolved 2,4-D resistance, increasing the LD50 from 16 to 138 g ha-1 . Along with 2,4-D resistance, cross-resistance to the ALS-inhibiting herbicides metosulam (4.0-fold) and chlorsulfuron (4.5-fold) was evident. Pretreatment of the 2,4-D-selected population with the cytochrome P450 inhibitor malathion restored chlorsulfuron to full efficacy, indicating that cross-resistance to chlorsulfuron was likely due to P450-catalysed enhanced rates of herbicide metabolism. CONCLUSION This study is the first to confirm the rapid evolution of auxinic herbicide resistance through the use of low doses of 2,4-D and serves as a reminder that 2,4-D must always be used at highly effective doses. With the introduction of transgenic auxinic-herbicide-resistant crops in the Americas, there will be a marked increase in auxinic herbicide use and therefore the risk of resistance evolution. Auxinic herbicides should be used only at effective doses and with diversity if resistance is to remain a minimal issue. © 2016 Society of Chemical Industry.
Global phosphorylation analysis of β-arrestin–mediated signaling downstream of a seven transmembrane receptor (7TMR)

β-Arrestin–mediated signaling downstream of seven transmembrane receptors (7TMRs) is a relatively new paradigm for signaling by these receptors. We examined changes in protein phosphorylation occurring when HEK293 cells expressing the angiotensin II type 1A receptor (AT1aR) were stimulated with the β-arrestin–biased ligand Sar1, Ile4, Ile8-angiotensin (SII), a ligand previously found to signal through β-arrestin–dependent, G protein-independent mechanisms. Using a phospho-antibody array containing 46 antibodies against signaling molecules, we found that phosphorylation of 35 proteins increased upon SII stimulation. These SII-mediated phosphorylation events were abrogated after depletion of β-arrestin 2 through siRNA-mediated knockdown. We also performed an MS-based quantitative phosphoproteome analysis after SII stimulation using a strategy of stable isotope labeling of amino acids in cell culture (SILAC). We identified 1,555 phosphoproteins (4,552 unique phosphopeptides), of which 171 proteins (222 phosphopeptides) showed increased phosphorylation, and 53 (66 phosphopeptides) showed decreased phosphorylation upon SII stimulation of the AT1aR. This study identified 38 protein kinases and three phosphatases whose phosphorylation status changed upon SII treatment. Using computational approaches, we performed system-based analyses examining the β-arrestin–mediated phosphoproteome including construction of a kinase-substrate network for β-arrestin–mediated AT1aR signaling. Our analysis demonstrates that β-arrestin–dependent signaling processes are more diverse than previously appreciated. Notably, our analysis identifies an AT1aR-mediated cytoskeletal reorganization network whereby β-arrestin regulates phosphorylation of several key proteins, including cofilin and slingshot. This study provides a system-based view of β-arrestin–mediated phosphorylation events downstream of a 7TMR and opens avenues for research in a rapidly evolving area of 7TMR signaling.
Optimal Reinsurance with Multiple Reinsurers: Competitive Pricing and Coalition Stability

We study economic pricing of reinsurance contracts via competition of an insurer with multiple reinsurers. All firms are endowed with distortion risk measures or expected exponential utilities. We require that contracts are Pareto optimal, individually rational, and satisfy a competition constraint that we call coalition stability. Indemnities are characterized by imposing Pareto optimality, as studied in the literature. In this paper, we characterize the corresponding premiums. There is a gain for the insurer due to the competition constraint. When the firms use distortion risk measures, this constraint yields stability for subcoalitions, which is a condition akin to the core in cooperative game theory. We show this gain for the insurer in closed form. Then, we derive that the premium is represented by a distortion premium function. If the firms use expected exponential utilities, the premium is represented by an exponential premium. We illustrate this premium function with the Mean Conditional Value-at-Risk.
Effects of 1,25‐dihydroxyvitamin D3 on the distribution of androgen and vitamin D receptors in human prostate neonatal epithelial cells

Although many studies have examined the mechanisms of 1,25‐dihydroxyvitamin D3 (calcitriol or 1,25 D) action in different prostate cancer cell lines, little is known regarding the influence of this steroid on the normal prostate. The presence of both VDR and AR in normal prostatic tissues raises the distinct possibility of an important role for this hormone in the normal gland. In order to ascertain the possible role of 1,25 D on both AR and VDR in the normal prostate, the effects of calcitriol and dihydrotestosterone (DHT) on the normal human neonatal prostatic epithelial cell line, 267B‐1, were examined. These studies were approached by focusing on how 1,25 D in the presence or absence of DHT affects the distribution of AR and VDR in the cytoplasmic and nuclear compartments of the cells in terms of their protein levels and DNA binding activities. Immunoblot analyses show that 1,25 D increases the AR protein level in both the cytoplasmic and nuclear fractions but not the VDR protein level. On the other hand, the gel shift assays demonstrate that 1,25 D increases both the AR– and VDR–DNA binding activities in the nuclear fraction, whereas there is no increase in DNA binding activities in the cytoplasmic fraction. Addition of DHT along with 1,25 D does not affect the DNA binding activities of both AR and VDR. Overall, these studies suggest that 1,25 D actions on the normal prostate cells may be mediated independently through AR and VDR, respectively. © 2002 Wiley‐Liss, Inc.
Low Grade Gliomas in Children

Gliomas represent the most common solid tumor of the nervous system, and can occur as both low and high-grade tumors. Current risk stratification and treatment approaches rely heavily on the morphological classification of gliomas whereby low-grade gliomas have an excellent prognosis, particularly pilocytic astrocytomas, while high-grade gliomas have a poor prognosis. The past decade has witnessed a dramatic increase in scholars’ knowledge of the biology of pediatric low-grade gliomas particularly through the advent of integrated genomics and next generation sequencing. Indeed, many of these biological advances are changing treatment paradigms, particularly in low-grade gliomas, where rationale targeted therapies are currently being explored in clinical trials. In this review the authors summarize the current approach to pediatric low grade gliomas and outline the biological advances over the past 10 years, which will be driving the next generation of clinical trials.
The Comparative Roles of Suppressor of Cytokine Signaling-1 and -3 in the Inhibition and Desensitization of Cytokine Signaling*

Negative feedback is a mechanism commonly employed in biological processes as a means of maintaining homeostasis. We have investigated the roles of suppressor of cytokine signaling (SOCS) proteins in regulating the kinetics of negative feedback in response to cytokine signaling. In mouse livers and bone marrow-derived macrophages, both interferon-γ (IFNγ) and interleukin-6 (IL-6) rapidly induced the tyrosine phosphorylation of signal transducer and activator of transcription-1 (STAT1) and STAT3. STAT3 tyrosine phosphorylation was bi-phasic in response to continuous IL-6 signaling. In macrophages lacking Socs3, however, continuous IL-6 signaling induced uniformly high levels of STAT3 tyrosine phosphorylation, and early IL-6-inducible genes were inappropriately expressed at intermediate time points. SOCS3 therefore imposes bi-phasic kinetics upon IL-6 signaling. Compared with Socs3 mRNA, Socs1 mRNA was induced relatively slowly, and SOCS1 simply attenuated the duration of IFNγ signaling. Surprisingly, heightened Socs1 mRNA expression but minimal STAT1 tyrosine phosphorylation was observed after prolonged stimulation with IFNγ, indicating that STAT1 may not play a large role in inducing Socs1 mRNA during steady-state IFNγ signaling. We also demonstrate that both SOCS1 and SOCS3 can desensitize primary bone marrow-derived macrophages to IFNγ and IL-6 signaling, respectively. Consistent with the kinetics with which Socs1 and Socs3 mRNAs were induced, SOCS3 desensitized cells to IL-6 rapidly, whereas SOCS1-mediated desensitization to IFNγ occurred at later time points. The kinetics with which SOCS proteins are induced by cytokine may therefore be a parameter that is “hard-wired” into specific cytokine signaling pathways as a means of tailoring the kinetics with which cells become desensitized.
The Potential for Technology in Brief Interventions for Substance Use, and During-Session Prediction of Computer-Delivered Brief Intervention Response

We first provide an overview of the potential of technology in the area of brief interventions for substance use and describe recent projects from our lab that are illustrative of that potential. Second, we present data from a study of during-session predictors of brief intervention response. In a sample of postpartum women (N = 39), several variables showed promise as predictors of later drug use, and a brief index derived from them predicted abstinence with a sensitivity of . 7 and a specificity of . 89. This promising approach and initial study findings support the importance of future research in this area.
Expression of c-erbB receptors and ligands in human nasal epithelium.

BACKGROUND The epidermal growth factor (EGF) family of growth factors plays an important role in maintenance and repair in a variety of epithelial tissues. However, very little is known about coexpression of these factors and their receptors, the c-erbB family of receptor tyrosine kinases, in human nasal epithelium. OBJECTIVE We sought to investigate the expression of these molecules in cultured nasal epithelial cells and nasal mucosa from healthy individuals. METHODS Identification of c-erbB receptors and their ligands was sought by using reverse transcription PCR, Western blotting, and immunohistochemistry. RESULTS Messenger RNA encoding the EGF receptors (EGFR) c-erbB2 and c-erbB3, but not c-erbB4, was detected in primary cultures of human nasal epithelial cells. Transcripts encoding EGF, heparin-binding EGF, transforming growth factor (TGF) alpha, and amphiregulin were also detected. Receptor and ligand expression was confirmed by using immunocytochemical staining of the cells and Western blotting of the cell lysates. Immunohistochemical analysis of tissue sections obtained from biopsy specimens of nasal mucosa revealed intense membrane staining for the EGFR within the respiratory nasal epithelium, which was predominantly localized at the level of the columnar epithelial layers. Similar staining patterns were observed for c-erbB2 and c-erbB3 in the respiratory nasal epithelium. Evidence for EGF, transforming growth factor alpha, heparin-binding EGF, amphiregulin, and betacellulin immunostaining in the nasal epithelium was also obtained; their staining patterns paralleled that of EGFR immunostaining. CONCLUSION Colocalization of c-erbB receptors and ligands establishes a basis on which to investigate c-erbB receptor- mediated effects in human nasal epithelium.
Intradorsal hippocampal microinjection of lithium reverses morphine-induced impairment of memory in mice: interactions with dopamine receptor mechanism(s)

In this study, the influence of lithium administration on morphine-induced memory impairment and possible interactions with dopamine receptor mechanism have been investigated. Considering that the dorsal hippocampus is involved in memory, lithium and dopamine agents were injected into the CA1 regions of this site (intra-CA1). For memory assessment, a one-trial step-down inhibitory avoidance task was used in adult male mice. The results showed that posttraining subcutaneous administration of morphine (5 mg/kg) decreased the step-down latency on the test day, and this effect was reversed by pretest administration of the drug, which may be a form of morphine state-dependent learning. Interestingly, pretest intra-CA1 microinjection of different doses of lithium (2 and 4 μg/mouse) reversed memory impairment induced by posttraining morphine (5 mg/kg, subcutaneously). In contrast, pretest intra-CA1 administration of either D1 receptor antagonist SCH23390 (0.01–1 μg/mouse) or D2 receptor antagonist sulpiride (5–10 μg/mouse) inhibited the improvement of memory retrieval by lithium (4 μg/mouse, intra-CA1). Single pretest administration of SCH23390 or sulpiride neither elicited any response, nor reversed morphine-induced amnesia. In conclusion, it can be suggested that the dorsal hippocampal dopaminergic system is involved in the improving response of lithium on morphine-induced amnesia.
[Clinical study of human cytomegalovirus infection in colony forming unit-megakaryocyte in patients with idiopathic thrombocytopenic purpura].

OBJECTIVE Idiopathic thrombocytopenic purpura (ITP) is a hemorrhagic disease in children with blood platelets redundant destruction caused by chaotic immunological mechanism. However, some patients with ITP with negative platelet-associated antibody and ineffective adrenal cortical hormone therapy probably have special pathogenesis. It is indicated that the human cytomegalovirus (HCMV) can incubate in haemopoietic stem cell/ancestral cell to inhibit its generation and differentiation. Therefore, the study was designed to investigate HCMV-late mRNA expression in megakaryoblast for the purpose of examining the pathogenesis of ITP and to examine the effectiveness of ganciclovir on ITP. METHODS Colony forming unit-megakaryocyte (CFU-MK) of 46 ITP patients with HCMV infection were incubated. Reverse transcription-polymerase chain reaction (RT-PCR) was subsequently used for HCMV-late mRNA detection. Ganciclovir therapy was given to both positive group and negative group for comparison of therapeutic effectiveness. RESULTS Nineteen out of 46 CFU-MK culture cell specimens with positive HCMV-DNA by PCR or positive CMV-IgM by enzyme linked immunosorbent assay (ELISA) from serum of peripheral blood showed positive for HCMV-late mRNA. While, the remaining 27 were negative. Sixteen positive responders to ganciclovir therapy were observed amongst those with positive HCMV-DNA. Whereas, only 4 positive responders to ganciclovir therapy were noticed amongst those with negative HCMV-DNA. The curative effectiveness in positive group was significantly higher than that in negative group (P < 0.01). CONCLUSION HCMV can directly infect CFU-MK, which might be one of the mechanisms responsible for ITP. Ganciclovir is an effective therapy resulting in an increase in thrombocyte in ITP patients whose HCMV-late mRNA was positive in their CFU-MK.
No evidence for genetic association of interferon regulatory factor 1 in juvenile idiopathic arthritis.

OBJECTIVE Juvenile idiopathic arthritis (JIA) comprises several clinically distinct subgroups and is the most widespread cause of chronic childhood disability. A significant association between JIA and a polymorphism in the interferon regulatory factor 1 (IRF-1) gene has previously been reported, implicating IRF1 in disease susceptibility. The aim of this study was to replicate the IRF1 association in JIA using single-marker and haplotype analyses in a case-control study, using control subjects different from those in the previous study and a larger cohort of patients (n = 765). METHODS DNA from 765 patients with JIA and 508 unaffected control subjects was genotyped for 4 single-nucleotide polymorphisms in the IRF-1 gene. Association of genotypes at the IRF1 loci was assessed using single-marker and haplotype analyses. RESULTS No significant differences in genotype frequency or allele frequency were observed between patients and control subjects. CONCLUSION This replication study used a much larger patient cohort to examine the association of IRF1 in JIA. However, despite the increased statistical power, we observed no significant association for IRF1 markers, either individually or as haplotypes. It is therefore unlikely that this gene is involved in JIA susceptibility.
Mechanism of the paradoxical, inhibitory effect of phenobarbital on hepatocarcinogenesis initiated in infant B6C3F1 mice with diethylnitrosamine.

Phenobarbital (PB), a classical rodent hepatopromoter, remarkably enhances hepatocarcinogenesis initiated by diethylnitrosamine (DEN) in adult B6C3F1 mice. However, it is also known to strongly inhibit liver tumor development in the B6C3F1 mice initiated with DEN in their infancy. The present study aimed to elucidate the unknown biological mechanisms for this paradoxical, inhibitory effect of PB on B6C3F1 mouse hepatocarcinogenesis. Male 12-day-old infant B6C3F1 mice were injected i.p. with DEN and, at 6 weeks of age, divided into PB-treated (PB+ group) and untreated (PB- group) animals. At 24 weeks, PB treatment was ceased for half of the PB+ animals (PB+/- group) and started for half of the PB- animals (PB-/+ group). Finally, all mice were sacrificed at 36 weeks and examined for the development of liver tumors. The mean multiplicity of gross tumors in the PB+ group was only one-fifteenth of that for the PB- group. PB-/+ animals developed fewer than half of the tumors found in PB- mice, indicating that the PB effect depends solely on the treatment duration, rather than the animal age. The effect was proven to be reversible, because the mean tumor multiplicity for the PB+/- group was seven times larger than that for the PB+ group. Stereological analysis revealed the mean volume of hepatocellular proliferative lesions in the PB- animals to be 7.7- and 4.1-fold the values for the PB+ and PB-/+ groups, respectively. The mean proliferating cell nuclear antigen-labeling indices for hepatocellular adenomas in PB+ and PB-/+ animals were also one-third of that for tumors in PB- animals, whereas no significant differences were observed with regard to the mean apoptotic index. In conclusion, the inhibitory effect of PB seemed to be primarily caused by the suppression of tumor cell proliferation. Irrespective of the group, most lesions observed were basophilic hepatocellular adenomas or foci, positive for Bcl-2 oncoprotein. They were thus distinct from the eosinophilic Bcl-2- lesions that predominate with PB promotion after the initiation of adult B6C3F1 mice. This age-dependent nature of initiation, together with the differential responses of Bcl-2+ and Bcl-2- lesions, may be responsible for the apparently contradictory outcomes of PB treatment in infant and adult B6C3F1 mice.
A Randomized Wait-List Controlled Trial of Feasibility and Efficacy of an Online Mindfulness–Based Cancer Recovery Program: The eTherapy for Cancer Applying Mindfulness Trial

Objective A treatment-as-usual randomized wait-list controlled trial was conducted to investigate the feasibility and impact of an online synchronous Mindfulness-Based Cancer Recovery (MBCR) group program for underserved distressed cancer survivors. Methods Sixty-two men and women exhibiting moderate to high distress within 3 years of completing primary cancer treatment without access to in-person MBCR were randomized to either immediate online MBCR (n = 30) or to wait for the next available program (n = 32). Participants completed questionnaires preintervention and postintervention or wait period online. Program evaluations were completed after MBCR. Feasibility was tracked through monitoring eligibility and participation through the protocol. Intent-to-treat mixed-model analyses for repeated measures were conducted. Results Feasibility targets for recruitment and retention were achieved, and participants were satisfied and would recommend online MBCR. There were significant improvements and moderate Cohen d effect sizes in the online MBCR group relative to controls after MBCR for total scores of mood disturbance (d = 0.44, p = .049), stress symptoms (d = 0.49, p = .021), spirituality (d = 0.37, p = .040), and mindfully acting with awareness (d = 0.50, p = .026). Main effects of time were observed for posttraumatic growth and remaining mindfulness facets. Conclusions Results provide evidence for the feasibility and efficacy of an online adaptation of MBCR for the reduction of mood disturbance and stress symptoms, as well as an increase in spirituality and mindfully acting with awareness compared with a treatment-as-usual wait-list. Future study using larger active control RCT designs is warranted. Trial Registration: Clinical Trials.gov: NCT01476891.
Preparation and transfusion of canine platelet concentrates.

A protocol was developed for preparation of platelet concentrates (PC) to support thrombocytopenic dogs. Four clinically normal dogs with platelet counts that ranged from 200 to 330 x 10(9) platelets/L were used as donors. One unit (450 ml) of blood was collected by venipuncture into a double blood bag. Whole blood (WB) was centrifuged for 4 minutes at 1,000 x g (braking time = 2 minutes, 30 seconds) to prepare platelet-rich plasma (PRP). The PRP was expressed into the satellite bag and was centrifuged for 10 minutes at 2,000 x g (braking time = 2 minutes, 36 seconds). The platelet-poor plasma was expressed, leaving 40 to 70 ml of plasma and the pelleted platelets in the satellite bag. The resulting PC was left undisturbed for 60 minutes to promote disaggregation, and the platelets were then resuspended by gentle manual agitation. Forty-eight PC were prepared. Mean (+/- SD) platelet yield from WB to PRP was 78 (+/- 13)% (range, 35 to 97%); yield from PRP to PC was 94 (+/- 6)% (range, 75 to 100%); and overall yield (PC from WB) was 74 (+/- 13)% (range, 36 to 91%). Mean PC platelet count was 8.0 (+/- 3.0) x 10(10) platelets/PC (range, 2.3 to 13.4 x 10(10) platelets/PC). The WBC content was 0.1 to 2.3 x 10(9) platelets/PC, representing 3 to 74% of WBC in the WB. Hematocrit was 0.1 to 26.2%. Results of bacterial and fungal culturing were negative. The PC were irradiated (18 Gy) and transfused to 5 cross-matched dogs undergoing bone marrow transplantation that developed profound thrombocytopenia of up to 8 weeks' duration. (ABSTRACT TRUNCATED AT 250 WORDS)