Miracle-dz/UniFAR-FTUs huggingface dataset:
AKT Facilitates EGFR Trafficking and Degradation by Phosphorylating and Activating PIKfyve

Receptor tyrosine kinases limit their own activity by stimulating kinases that promote trafficking of the receptors to the lysosome. Promoting One’s Own Demise Mutations in the genes encoding epidermal growth factor receptors (EGFRs) are linked to various cancers in humans. Understanding how signaling through EGFRs and related receptors is terminated can provide potential therapeutic targets. Ligand binding to EGFRs leads to the activation of the kinase AKT, and Er et al. found that AKT phosphorylated and activated the kinase PIKfyve, which is involved in vesicle trafficking. PIKfyve enhanced the degradation of EGFR, and inhibition of AKT resulted in an increase in EGFR abundance and downstream signaling. Thus, EGFR activity stimulates a pathway that brings about termination of its signaling. Epidermal growth factor receptor (EGFR) is a receptor tyrosine kinase (RTK) that controls cell proliferation, growth, survival, metabolism, and migration by activating the PI3K (phosphatidylinositol 3-kinase)–AKT and ERK (extracellular signal–regulated kinase)–RSK (ribosomal S6 kinase) pathways. EGFR signaling to these pathways is temporally and spatially regulated. Endocytic trafficking controls the access of EGFR to these downstream effectors and also its degradation, which terminates EGFR signaling. We showed that AKT facilitated the endocytic trafficking of EGFR to promote its degradation. Interfering with AKT signaling reduced both EGFR recycling and the rate of EGFR degradation. In AKT-impaired cells, EGFRs were unable to reach the cell surface or the lysosomal compartment and accumulated in the early endosomes, resulting in prolonged signaling and increased activation of ERK and RSK. Upon EGF stimulation, AKT phosphorylated and activated the kinase PIKfyve [FYVE-containing phosphatidylinositol 3-phosphate 5-kinase], which promoted vesicle trafficking to lysosomes. PIKfyve activation promoted EGFR degradation. Similar regulation occurred with platelet-derived growth factor receptor (PDGFR), suggesting that AKT phosphorylation and activation of PIKfyve is likely to be a common feedback mechanism for terminating RTK signaling and reducing receptor abundance.
Negotiating Language Policy and Practice

Arizona language policy now requires English learners (ELs) to enroll in English language development (ELD) classrooms for 4 hr of skill-based, English-only instruction. In this article, I describe Arizona teachers’ interpretation and negotiation of language policy and practice during this time of change to more restrictive mandates. I conducted this qualitative case study with a teacher study group comprised of six ELD teachers and one instructional coach from an urban elementary school during the first semester of language policy implementation. Using discourse analysis of individual interviews, study group dialogue, and institutional documentation, I investigated teachers’ talk as they grappled with restrictive policy mandates and effective classroom practice. Findings indicated that teachers negotiated the cultural models inherent in the institutional policy in the study group setting. In the contemporary context of restrictive educational policies, implications for stakeholders center on professional and collaborative support for educators.
The glue of (ab)normal mental life: Networks of interacting thoughts, feelings and behaviors

The pivotal problem of comorbidity research lies in the psychometric foundation it rests on, that is, latent variable theory, in which a mental disorder is viewed as a latent variable that causes a constellation of symptoms. From this perspective, comorbidity is a (bi)directional relationship between multiple latent variables. We argue that such a latent variable perspective encounters serious problems in the study of comorbidity, and offer a radically different conceptualization in terms of a network approach, where comorbidity is hypothesized to arise from direct relations between symptoms of multiple disorders. We propose a method to visualize comorbidity networks and, based on an empirical network for major depression and generalized anxiety, we argue that this approach generates realistic hypotheses about pathways to comorbidity, overlapping symptoms, and diagnostic boundaries, that are not naturally accommodated by latent variable models: Some pathways to comorbidity through the symptom space are more likely than others; those pathways generally have the same direction (i.e., from symptoms of one disorder to symptoms of the other); overlapping symptoms play an important role in comorbidity; and boundaries between diagnostic categories are necessarily fuzzy. Adapted from: Cramer, A. O. J., Waldorp, L. J., van der Maas, H. L. J., & Borsboom, D. (2010). Comorbidity: A network perspective. Behavioral and Brain Sciences, 33, 137-150.
GLYCOGEN SYNTHASE KINASE 3&bgr; AS A TARGET FOR THE THERAPY OF SHOCK AND INFLAMMATION

After the discovery that glycogen synthase kinase (GSK) 3&bgr; plays a fundamental role in the regulation of the activity of nuclear factor &kgr;B, a number of studies have investigated the effects of this protein kinase in the regulation of the inflammatory process. The GSK-3&bgr; inhibition, using genetically modified cells and chemically different pharmacological inhibitors, affects the regulation of various inflammatory mediators in vitro and in vivo. Insulin, an endogenous inhibitor of GSK-3 in the pathway leading to the regulation of glycogen synthase activity, has recently been clinically used in the therapy for septic shock. The beneficial anti-inflammatory effects of insulin in preclinical and clinical studies could possibly be due, at least in part, to the inhibition of GSK-3 and not directly correlated to the regulation of blood glucose. We describe the latest studies describing the effects of GSK-3 inhibition as potential target of the therapy for diseases associated with inflammation, ischemia/reperfusion, and shock.
The Cynical Americans: Living and Working in an Age of Discontent and Disillusion

Provides a comprehensive analysis of cynicism in the workforce and tells how to identify and successfully combat it in organizations. Offers case studies of companies ranging from Ben and Jerry's Ice Cream to Unisys and Caterpillar Tractor to show how businesses of all types and sizes can effectively rebuild trust and restore confidence in organizational life.
Protective Effects of Morus alba Leaves Extract on Ocular Functions of Pups from Diabetic and Hypercholesterolemic Mother Rats

Phytotherapy is frequently considered to be less toxic and free from side effects than synthetic drugs. Hence, the present study was designed to investigate the protective use of crude water extract of Morus alba leaves on ocular functions including cataractogenesis, biochemical diabetic and hypercholesterolemic markers, retinal neurotransmitters and retinopathy of rat pups maternally subjected to either diabetes and/or hypercholesterolemia. Application of crude water extract of Morus alba resulted in amelioration of the alterations of maternal serum glucose, LDL, HDL, total cholesterol and creatine phosphokinase activity as well as retinal neurotransmitters including acetylcholine (ACE), adrenaline (AD), nor-adrenaline (NAD), serotonin (5-HT), histamine (HS), dopamine (DA) and gamma amino butyric acid (GABA). The retina of pups of either diabetic and/or hypercholesterolemia mothers exhibited massive alterations of retinal neurotransmitters. The alterations of retinal neurotransmitters were correlated with the observed pathological alterations of retinal pigmented epithelium, photoreceptor inner segment and ganglion cells and increased incidence of DNA fragmentation and apoptosis cell death. However, protection with Morus alba extract led to amelioration of the pathological alterations of retinal neurons and estimated neurotransmitters. Furthermore, a striking incidence of cataract was detected in pups of either diabetic and/or hypercholesterolemic mothers. Highest cataractogenesis was observed in pups of combined -treated groups. Our data indicate that experimental maternal diabetes alone or in combination with hypercholesterolemia led to alteration in the ocular structures of their pups, with an increasing incidence of cataract and retinopathy, and the effects of the extract might be attributed to the hypoglycaemic, antihypercholesterolemic and anti-oxidative potential of flavonoids, the major components of the plant extract.
Caries experience associated to social and preventive factors in children of a pastoral community from Limeira-SP

Aim: To evaluate caries experience and prevalence associated to social and preventive factors in 3-6-year-old children of a Pastoral Community from Limeira, Brazil. Methods: A cross-sectional study was carried out through an epidemiologic research about the oral conditions of 110 children registered at the Children’s Pastoral Community from the city of Limeira, SP, Brazil. Intraoral examination was performed by a trained dentist and the parents/caregivers filled out a questionnaire in order to outline the children’s profile with respect to gender, parental education and oral health. Results: Differences related to gender were not detected (p= 0.3404). The most frequent periods of breastfeeding were 0 to 2 months (36.36%) and 2 to 6 months (35.45%), corresponding to 71.81% of the cases. The time bottle feeding pointed to two most frequent categories: 1) more than 12 months (35.45%) and 2) between 2 and 6 months (22.63%). Regarding parental education, the majority of the sample has not completed primary school (38.32%). It was observed a larger number of decayed teeth in male children (63.39%). Caries experience was significantly higher in children who were breastfed for only 2 months of life (41.96%). Children that did not use baby bottle or did not use a baby bottle for more than 1 year presented a smaller dmft, corresponding to 29.17% and 28.33%, respectively. Time of use of bottle and pacifier presented a significant association (p<0.05). Conclusions: The implementation of adequate strategies and actions is needed to reinforce oral health conditions in risk groups.
TRAP1 Controls Mitochondrial Fusion/Fission Balance through Drp1 and Mff Expression

Mitochondria are dynamic organelles that change in response to extracellular stimuli. These changes are essential for normal mitochondrial/cellular function and are controlled by a tight balance between two antagonistic pathways that promote fusion and fission. Although some molecules have been identified to mediate the mitochondrial fusion and fission process, the underlying mechanisms remain unclear. Tumor necrosis factor receptor-associated protein 1 (TRAP1) is a mitochondrial molecule that regulates a variety of mitochondrial functions. Here, we examined the role of TRAP1 in the regulation of morphology. Stable TRAP1 knockdown cells showed abnormal mitochondrial morphology, and we observed significant decreases in dynamin-related protein 1 (Drp1) and mitochondrial fission factor (Mff), mitochondrial fission proteins. Similar results were obtained by transient knockdown of TRAP1 in two different cell lines, SH-SY5Y neuroblastoma cells and KNS-42 glioma cells. However, TRAP1 knockdown did not affect expression levels of fusion proteins. The reduction in Drp1 and Mff protein levels was rescued following treatment with the proteasome inhibitor MG132. These results suggest that TRAP1 regulates the expression of fission proteins and controls mitochondrial fusion/fission, which affects mitochondrial/cellular function.
Testing the Acceptance Model of Intuitive Eating With College Women Athletes

Intuitive eating is an adaptive eating style that involves eating for physical rather than emotional reasons, reliance on internal hunger and satiety cues, and lack of restriction in eating. In our study, the authors tested the acceptance model of intuitive eating with 160 college women athletes from Division I and Division II schools, using path analysis and controlling for body mass index. Similar to a previous study with general college women, the model provided an excellent fit to the data. These results support the hypothesis that perceived acceptance from others indirectly contributes to intuitive eating through college women athletes’ attitudes toward their bodies. For college women athletes, body acceptance by coaches, trainers, and teammates predicted athletes’ own body appreciation, which in turn, predicted their eating style. These findings suggest ways for coaches and counselors to help women athletes enhance their body appreciation and improve their eating. These results also indicate the need for researchers to further explore women athletes’ eating styles and attitudes toward their bodies.
The pathogenesis of infection with minute virus of mice depends on expression of the small nonstructural protein NS2 and on the genotype of the allotropic determinants VP1 and VP2

Neonatal C3H/He mice were oronasally inoculated with similar doses of four genotypes of minute virus of mice (MVM). MVMp, a fibroblast-specific variant, caused an asymptomatic infection. MVM(1035), a chimera which had the allotropic determinant of virulent MVMi inserted onto an MVMp background, caused a lethal infection and renal papillary infarcts, the hallmark of MVMi infection. MVMi(NS2-1990), the virulent lymphocyte-specific variant mutated to eliminate NS2 synthesis, was infectious but caused an asymptomatic infection. Sequential virus titration, histology, in situ hybridization with a full-length MVMi genomic probe, and immunohistochemistry for viral capsid antigen were used to compare the pathogenesis of infection with the four MVM genotypes. Infectious virus was recovered from multiple organs of mice infected with MVMi, MVMp, and MVM(1035) but not from mice infected with MVMi(NS2-1990). MVMp titers were lower than MVMi titers in all organs except the intestine. MVM(1035) titers were higher than MVMi titers in all organs except the blood. MVMp was localized to connective tissue elements of the intestine, to cells in mesenteric lymph nodes, and rarely to cells in other organs. MVM(1035) was localized to multiple organs and shared the same target cells, endothelium, lymphoid cells, and hematopoietic cells, as MVMi. MVM(1035) also replicated in external germinal cells of the cerebellum and smooth muscle cells of the stomach and colon, which were not targets of MVMi or MVMp infection. MVMi(NS2-1990) replicated to a limited degree in some MVMi target organs.
Modern treatment in chronic lymphocytic leukemia: impact on survival and efficacy in high-risk subgroups

Treatment of chronic lymphocytic leukemia (CLL) has dramatically changed over the last years, with significant improvement in overall survival (OS) and increased efficacy in genetically defined “high‐risk” disease. Besides prospective clinical trials usually enrolling young and fit patients, retrospective studies were performed comparing the outcome of patients belonging to different age groups and showing longer survival in patients diagnosed in the most recent periods. In patients younger than 70 years the 10‐year relative survival was 43–53% in the 1980s as compared with 59–63% in the 2000s. Likewise, the 10‐year relative survival in patients >70 years was 22–42% in the 1980s and 46–55% in the 2000s. Improved outcome derived in part by the introduction of effective regimens in genetically defined “high‐risk” disease (i.e., 17p−, 11q−, TP53, NOTCH1, SF3B1 mutations), especially in the younger and/or fit patients. The unfavorable prognostic significance of 11q− was overcome by chemoimmunotherapy. High‐dose steroids with anti‐CD52 appeared to improve the response rate in 17p‐/TP53 mutated cases and allogeneic transplantation achieved prolonged disease control irrespective of high‐risk disease. Further improvement is being generated by the new anti‐CD20 obinutuzumab in the elderly and by mechanism‐based treatment using kinase‐targeting agents or anti‐BCL2 molecules yielding high‐response rate and impressive progression‐free survival in the chemorefractory setting as well as in previously untreated patients.
Can Management Strategy Minimize the Impact of Red Tape on Organizational Performance?

This study investigates the effects of red tape and strategy on organizational performance. Data come from 135 English local government authorities. Data are collected on several dimensions of red tape, three types of strategy (prospecting, defending, and reacting), and internal and external perceptual measures of organizational performance. The findings show that red tape lowers performance. The harmful effects of red tape are, however, mitigated by a strategic stance of prospecting. Defending has no effect on the impact of red tape on organizational performance, whereas reacting tends to amplify the harmful effects—thus worsening organizational performance. The primary implication of these findings is that public organizations should move toward more proactive strategies.
A general predictive model for estimating monthly ecosystem evapotranspiration

Accurately quantifying evapotranspiration (ET) is essential for modelling regional‐scale ecosystem water balances. This study assembled an ET data set estimated from eddy flux and sapflow measurements for 13 ecosystems across a large climatic and management gradient from the United States, China, and Australia. Our objectives were to determine the relationships among monthly measured actual ET (ET), calculated FAO‐56 grass reference ET (ETo), measured precipitation (P), and leaf area index (LAI)—one associated key parameter of ecosystem structure. Results showed that the growing season ET from wet forests was generally higher than ETo while those from grasslands or woodlands in the arid and semi‐arid regions were lower than ETo. Second, growing season ET was found to be converged to within ± 10% of P for most of the ecosystems examined. Therefore, our study suggested that soil water storage in the nongrowing season was important in influencing ET and water yield during the growing season. Lastly, monthly LAI, P, and ETo together explained about 85% of the variability of monthly ET. We concluded that the three variables LAI, P, and ETo, which were increasingly available from remote sensing products and weather station networks, could be used for estimating monthly regional ET dynamics with a reasonable accuracy. Such an empirical model has the potential to project the effects of climate and land management on water resources and carbon sequestration when integrated with ecosystem models. Copyright © 2010 John Wiley & Sons, Ltd.
Performance Antipatterns as Logical Predicates

The problem of interpreting the results of performance analysis is quite critical in the software performance domain. Mean values, variances, probability distributions are hard to interpret for providing feedback to software architects. Instead, what architects expect are solutions to performance problems, possibly in the form of architectural alternatives (e. g. split a software component in two components and re-deploy one of them). In a software performance engineering approach this path from analysis results to software alternatives still lacks of automation and is based on the skills and experience of analysts. In this paper we propose an automated approach for the performance feedback generation process based on performance antipatterns. To this aim, we model performance antipatterns as logical predicates and we provide a java engine, based on such predicates, that is able to detect performance antipatterns in an XML representation of the software system. Finally, we show the approach at work on a simple case study.
Diverse Thalamocortical Short-Term Plasticity Elicited by Ongoing Stimulation

To produce sensation, neuronal pathways must transmit and process stimulus patterns that unfold over time. This behavior is determined by short-term synaptic plasticity (STP), which shapes the temporal filtering properties of synapses in a pathway. We explored STP variability across thalamocortical (TC) synapses, measuring whole-cell responses to stimulation of TC fibers in layer 4 neurons of mouse barrel cortex in vitro. As expected, STP during stimulation from rest was dominated by depression. However, STP during ongoing stimulation was strikingly diverse across TC connections. Diversity took the form of variable tuning to the latest interstimulus interval: some connections responded weakly to shorter intervals, while other connections were facilitated. These behaviors did not cluster into categories but formed a continuum. Diverse tuning did not require disynaptic inhibition. Hence, monosynaptic excitatory lemniscal TC connections onto layer 4 do not behave uniformly during ongoing stimulation. Each connection responds differentially to particular stimulation intervals, enriching the ability of the pathway to convey complex, temporally fluctuating information.
Evidence of syntactic working memory usage in MEG data

While reading times are often used to measure working memory load, frequency effects (such as surprisal or n-gram frequencies) also have strong confounding effects on reading times. This work uses a naturalistic audio corpus with magnetoencephalographic (MEG) annotations to measure working memory load during sentence processing. Alpha oscillations in posterior regions of the brain have been found to correlate with working memory load in non-linguistic tasks (Jensen et al., 2002), and the present study extends these findings to working memory load caused by syntactic center embeddings. Moreover, this work finds that frequency effects in naturally-occurring stimuli do not significantly contribute to neural oscillations in any frequency band, which suggests that many modeling claims could be tested on this sort of data even without controlling for frequency effects.
Impaired long-term stability of CA1 place cell representation in mice lacking the transcription factor zif268/egr1

Zif268 is a transcriptional regulator that plays a crucial role in maintenance of the late phases of hippocampal long-term potentiation (LTP) and consolidation of spatial memories. Because the hippocampal place cell system is essential for long-term spatial memory, we tested the hypothesis that zif268 is required for long-term stability of hippocampal place cell representations by recording CA1 place cells in mice lacking zif268. We found that zif268 gene deletion destabilized the representation of a familiar environment after exposure to a novel environment and impaired the long-term (24 h), but not short-term (1 h), stability of newly formed representations. These impairments could be rescued by repeated exposure to the novel environment, however. These results indicate that zif268 contributes to the long-term stability of spatial representations in CA1 and support the notion that the long-term stability of place cell representations requires transcription-dependent mechanisms similar to those observed in LTP.