Miracle-dz/UniFAR-FTUs huggingface dataset:
Aurora‐A kinase phosphorylation of Aurora‐A kinase interacting protein (AIP) and stabilization of the enzyme‐substrate complex

Aurora‐A is an oncogenic kinase that plays essential roles in mitosis as well as cell survival. Aurora‐A interacting protein (AIP) was identified as a negative regulator of Aurora‐A with its ectopic over expression inducing destabilization of Aurora‐A protein. Here we present evidence that in human cells, contrary to the earlier report, AIP functions in stabilizing rather than destabilizing Aurora‐A. Furthermore, AIP is phosphorylated on Serine 70 by Aurora‐A but not Aurora‐B and expression of phosphorylation mimic mutant of AIP results in prolonged protein stability compared to unphosphorylatable mutant. We observed that when co‐expressed with AIP, protein levels of both Aurora‐A and Aurora‐B are markedly elevated regardless of their kinase activities and phosphorylation state of AIP. Interaction of Aurora kinases with AIP is necessary for this elevated stability. This phenomenon is commonly detected in several human cancer cell lines used in this study. Depletion of AIP by RNA interference decreased Aurora‐A but not Aurora‐B in two of the three cell lines analyzed, indicating that under physiological condition, AIP functions in stabilization of Aurora‐A but not Aurora‐B, though this regulation may be dependent on additional factors as well. Further, AIP siRNA induced cell cycle arrest at G2/M, which is consistent with anticipated loss of function of Aurora‐A in these cells. Thus, our study provides the first evidence of a role for AIP in G2/M cell cycle progression by cooperatively regulating protein stabilization of its up‐stream regulator, Aurora‐A kinase through protein–protein interaction as well as protein phosphorylation. J. Cell. Biochem. 102: 1318–1331, 2007. © 2007 Wiley‐Liss, Inc.
Changes in EEG Cross-Frequency Coupling During Cognitive Behavioral Therapy for Social Anxiety Disorder

Coupling between EEG delta and beta oscillations is enhanced among anxious and healthy individuals during anticipatory anxiety. EEG coupling patterns associated with psychotherapy have not yet been quantified in socially anxious individuals. In this study, we used a double baseline, repeated measures design, in which 25 adults with a principal diagnosis of social anxiety disorder completed 12 weekly sessions of standardized group cognitive behavioral therapy and four EEG assessments: two at pretreatment, one at midtreatment, and one at posttreatment. Treatment was associated with reductions in symptom severity across multiple measures and informants, as well as reductions in delta-beta coupling at rest and during speech anticipation. Moreover, the clinical group exhibited greater coupling at pretreatment than did post hoc control participants with low social anxiety. The EEG cross-frequency profiles in the clinical group normalized by the posttreatment assessment. These findings provide evidence of concomitant improvement in neural and behavioral functioning among socially anxious adults undergoing psychotherapy.
Concentration of remifentanil needed for tracheal intubation with sevoflurane at 1 MAC in adult patients

Background and objective: Inhalation induction with sevoflurane provides acceptable conditions for tracheal intubation. Opioids significantly decrease the alveolar concentration needed to achieve tracheal intubation. The purpose of this study was to determine the target concentration of remifentanil providing excellent conditions for tracheal intubation with sevoflurane at 1 minimum alveolar concentration without muscle relaxant. Methods: Twenty‐four consecutive patients, aged 18‐50 yr, ASA I or II, were studied. Induction of anaesthesia was performed with sevoflurane at age‐adjusted minimum alveolar concentration. Remifentanil was simultaneously administered using target‐controlled infusion with the Minto model. Target plasma concentration of remifentanil was selected for each patient according to an up‐and‐down method. Results: The mean target concentration of remifentanil for successful tracheal intubation was 3.3 ng mL−1 (95% confidence interval: 2.6‐3.9 ng mL−1). Arterial pressure, heart rate and bispectral index did not increase after tracheal intubation in the group of patients with successful intubation. Conclusions: Remifentanil at 3.3 ng mL−1 together with sevoflurane at 1 minimum alveolar concentration provides excellent conditions for tracheal intubation in 50% of patients.
Prevalence and risk factors of hyperprolactinemia among patients with various psychiatric diagnoses and medications

Abstract Objectives: Hyperprolactinemia is a common adverse event associated with psychotropic medications (mainly antipsychotics) used in the management of schizophrenia and bipolar disorders. The aim of this study was to estimate the prevalence of hyperprolactinemia in psychiatric patients and to evaluate its association with various psychiatric diagnoses and the use of various psychotropic medications. Methods: A cross-sectional observational study was conducted between July 2012 and June 2014. Patients were recruited from a number of hospitals located in the five regions of Saudi Arabia. Hyperprolactinemia was defined as blood prolactin levels >25 ng/mL in females and >20 ng/mL in males, regardless of the presence of symptoms. Results: A total of 997 patients (553 males and 444 females) were included in the current analysis. The average blood prolactin level was 32.6 ± 44.1 ng/mL, with higher levels among females than males (42.9 ± 61.3 versus 24.4 ± 18.6, p < .001). The prevalence of hyperprolactinemia was 44.3%, with no significant gender difference (41.9% in females versus 46.3% in males, p = .164) but with huge variability according to individual antipsychotic and other psychotropic medications. In the multivariate analysis adjusted for demographic and clinical characteristics, hyperprolactinemia was independently and positively associated with using antipsychotic medications (OR = 2.08, 1.26–3.42, p = .004). Additionally, previous hospitalisation, diabetes and hypothyroidism were positively associated, whereas having primary depressive disorders was negatively associated. Conclusions: We report a high prevalence of hyperprolactinemia among a large sample of psychiatric patients in Saudi Arabia, which was linked to the use of antipsychotic medications. Routine measurement of blood prolactin levels for all patients maintained on antipsychotic agents is recommended, regardless of symptoms.
Dopamine dependency for acquisition and performance of Pavlovian conditioned response

Significance Dopaminergic signaling is critical for many reward-related processes, including learning associations between stimuli and rewards (“Pavlovian learning”). Behavioral responses to reward-associated stimuli have been described as being initially directed either at the stimulus itself (“sign tracking”) or at the location of reward delivery (“goal tracking”). Although other studies have demonstrated that dopaminergic signaling is crucial for sign tracking, its role for goal-tracking behavior is less clear. Our approach uses genetic manipulations that allow determining whether dopamine is required for learning goal tracking and also which dopaminergic projections are most relevant for this behavior. Moreover, we report that instrumental learning can facilitate Pavlovian learning in mice that are impaired in Pavlovian learning but not in instrumental learning. During Pavlovian conditioning, pairing of a neutral conditioned stimulus (CS) with a reward leads to conditioned reward-approach responses (CRs) that are elicited by presentation of the CS. CR behaviors can be sign tracking, in which animals engage the CS, or goal tracking, in which animals go to the reward location. We investigated CR behaviors in mice with only ∼5% of normal dopamine in the striatum using a Pavlovian conditioning paradigm. These mice had severely impaired acquisition of the CR, which was ameliorated by pharmacological restoration of dopamine synthesis with l-dopa. Surprisingly, after they had learned the CR, its expression decayed only gradually in following sessions that were conducted without l-dopa treatment. To assess specific contributions of dopamine signaling in the dorsal or ventral striatum, we performed virus-mediated restoration of dopamine synthesis in completely dopamine-deficient (DD) mice. Mice with dopamine signaling only in the dorsal striatum did not acquire a CR, whereas mice with dopamine signaling only in in the ventral striatum acquired a CR. The CR in mice with dopamine signaling only in the dorsal striatum was restored by subjecting the mice to instrumental training in which they had to interact with the CS to obtain rewards. We conclude that dopamine is essential for learning and performance of CR behavior that is predominantly goal tracking. Furthermore, although dopamine signaling in the ventral striatum is sufficient to support a CR, dopamine signaling only in the dorsal striatum can also support a CR under certain circumstances.
One-dimensional nanowire assembly based on oriented polymer nanofibers

We develop a simple method for the parallel assembly of nanowires (NWs) based on oriented polymer nanofiber films. The nanowires dispersed in solution are aligned at the central space of parallel nanochannels formed by the well-oriented nanofibers as a result of the capillarity. Then, a general contact printing is used to realize the transfer of the nanowires from the donor nanofiber film to a receiver substrate. The mechanism involving ordered alignment of nanowires on oriented polymer nanofiber films was investigated based on the experimental result. This simple method can be served as a general approach and found a wide range of applications in the fabrication of NW-based devices.
In vitro evaluation of the "replica technique" in the measurement of the fit of Procera crowns.

AIM The objective of this study was to compare the film thickness of a light body polyvinylsiloxane addition silicone impression material using the "replica technique" (RT) to the film thickness resulting from the cementation of Procera copings. METHODS AND MATERIALS Twenty Procera copings were fabricated on ten casts each having one central incisor and one premolar. The thickness of the light body was first measured using the RT; then on the same casts dies were cemented with glass-ionomer cement, sawed, and the film thickness of cement was measured. These two materials were expected to behave differently under stress according to their respective physical properties. RESULTS The thickness of silicone material did not differ significantly from that of the glass-ionomer cement used in this experiment. Also, when the two groups of central incisors and premolars were taken separately, at three different areas (occlusal, axial, and cervical), no significant difference was found. Only when each surface (buccal, palatal, mesial, and distal) was compared separately at the cervical area, some significant differences between the two techniques was detected. CONCLUSION Within the limitations of this study, the RT is an accurate and reliable technique that can simulate crown gap space after cementation. CLINICAL SIGNIFICANCE The RT is reliable for evaluating cement thickness at the marginal and internal gaps of Procera AllCeram crowns during try-in sessions.
Snail promotes cell migration through PI3K/AKT-dependent Rac1 activation as well as PI3K/AKT-independent pathways during prostate cancer progression

Snail, a zinc-finger transcription factor, induces epithelial-mesenchymal transition (EMT), which is associated with increased cell migration and metastasis in cancer cells. Rac1 is a small G-protein which upon activation results in formation of lamellipodia, the first protrusions formed by migrating cells. We have previously shown that Snail promotes cell migration through down-regulation of maspin tumor suppressor. We hypothesized that Snail's regulation of cell migration may also involve Rac1 signaling regulated by PI3K/AKT and/or MAPK pathways. We found that Snail overexpression in LNCaP and 22Rv1 prostate cancer cells increased Rac1 activity associated with increased cell migration, and the Rac1 inhibitor, NSC23766, could inhibit Snail-mediated cell migration. Conversely, Snail downregulation using shRNA in the aggressive C4–2 prostate cancer cells decreased Rac1 activity and cell migration. Moreover, Snail overexpression increased ERK and PI3K/AKT activity in 22Rv1 prostate cancer cells. Treatment of Snail-overexpressing 22Rv1 cells with LY294002, PI3K/AKT inhibitor or U0126, MEK inhibitor, decreased cell migration significantly, but only LY294002 significantly reduced Rac1 activity, suggesting that Snail promotes Rac1 activation via the PI3K/AKT pathway. Furthermore, 22Rv1 cells overexpressing Snail displayed decreased maspin levels, while inhibition of maspin expression in 22Rv1 cells with siRNA, led to increased PI3K/AKT, Rac1 activity and cell migration, without affecting ERK activity, suggesting that maspin is upstream of PI3K/AKT. Overall, we have dissected signaling pathways by which Snail may promote cell migration through MAPK signaling or alternatively through PI3K/AKT-Rac1 signaling that involves Snail inhibition of maspin tumor suppressor. This may contribute to prostate cancer progression.
Quantifying risk over the life course – latency, age‐related susceptibility, and other time‐varying exposure metrics

Identification of the latency period and age‐related susceptibility, if any, is an important aspect of assessing risks of environmental, nutritional, and occupational exposures. We consider estimation and inference for latency and age‐related susceptibility in relative risk and excess risk models. We focus on likelihood‐based methods for point and interval estimation of the latency period and age‐related windows of susceptibility coupled with several commonly considered exposure metrics. The method is illustrated in a study of the timing of the effects of constituents of air pollution on mortality in the Nurses' Health Study. Copyright © 2016 John Wiley & Sons, Ltd.
Contrast enhanced magnetic resonance imaging of the terminal ileum in children with Crohn’s disease

Background and aims: Recently, magnetic resonance imaging (MRI) has been introduced in the diagnosis of patients with inflammatory bowel disease (IBD). However, it is still rarely reported in paediatric IBD. We studied the diagnostic value of gadolinium enhanced MRI in revealing inflammation of the distal ileum in children with Crohn’s disease (CD) and in differentiating them from patients with other inflammatory diseases of the gut. MRI was performed using a polyethylene glycol (PEG) solution as oral contrast agent to distend the small bowel (CE-PEG-MRI). Subjects and methods: Seventy five consecutive patients (median age 13.6 years, range 8–17) with suspected CD underwent ileocolonoscopy with biopsy and CE-PEG-MRI. CD activity was measured by the paediatric Crohn’s disease activity index (PCDAI). CE-PEG-MRI was evaluated with an overall score calculated, taking into account both wall thickness and contrast enhancement. Results: Active CD with distal ileitis was diagnosed in 26 cases, active ulcerative colitis (UC) in 18, and spondyloarthropathy and indeterminate ileocolitis in 11; 20 children served as controls. In all CD patients, CE-PEG-MRI revealed a marked ileal involvement with increased wall thickness and parietal contrast enhancement and showed a high concordance with endoscopy and histology, whereas the test was negative in all controls. Of the 18 UC patients, CE-PEG-MRI was negative in 15 and showed a mild parietal contrast enhancement of the terminal ileum in only three of seven patients with backwash ileitis. Among the group of spondyloarthropathy patients, six had mucosal erosions and five mild superficial ileitis: CE-PEG-MRI was negative in four and revealed only mild parietal contrast enhancement of the ileal wall in seven. CE-PEG-MRI did not show an increase in wall thickness of the distal ileum in any of the UC or spondyloarthropathy patients. The sensitivity and specificity of CE-PEG-MRI related to the presence of erosive ileitis, as documented by endoscopy, were 84% and 100%, respectively. In addition, the test correlated markedly with endoscopy and histology in the entire population (r=0.94; r=0.95, respectively) as well as with the PCDAI in CD patients (r=0.91). Conclusions: In children with active CD, CE-PEG-MRI is a very sensitive and specific test for the detection of distal ileitis and for differentiation from other inflammatory diseases of the gut. The test could also be useful for the firstline diagnostic approach in children with suspected CD. The high correlation of CE-PEG-MRI with ileal endoscopy and histology as well as with PCDAI makes this test of great interest for future studies as a tool for monitoring the clinical course and the effect of therapy in CD patients.
System simulation of adaptive I/Q mismatch compensation method using SystemC-AMS

Insufficient image-rejection due to I/Q mismatch considerably degrades the performance of modern wireless communication systems. This paper presents a SystemC-AMS front-to back-end modeling approach in a Low-IF receiver system with a digital adaptive filter for I/Q mismatch compensation. With the proposed approach, the non-ideal behavioral of the analog building blocks concerning I/Q imbalance is mapped and the performance of compensation filter based on LMS algorithm can be verified efficiently during the system simulation. Simulation results confirmed the feasibility of the implementation of such a compensation filter for increasing the image rejection performance of the Low-IF receiver front end.
Stabilizing selection on individual pattern elements of aposematic signals

Warning signal variation is ubiquitous but paradoxical: low variability should aid recognition and learning by predators. However, spatial variability in the direction and strength of selection for individual elements of the warning signal may allow phenotypic variation for some components, but not others. Variation in selection may occur if predators only learn particular colour pattern components rather than the entire signal. Here, we used a nudibranch mollusc, Goniobranchus splendidus, which exhibits a conspicuous red spot/white body/yellow rim colour pattern, to test this hypothesis. We first demonstrated that secondary metabolites stored within the nudibranch were unpalatable to a marine organism. Using pattern analysis, we demonstrated that the yellow rim remained invariable within and between populations; however, red spots varied significantly in both colour and pattern. In behavioural experiments, a potential fish predator, Rhinecanthus aculeatus, used the presence of the yellow rims to recognize and avoid warning signals. Yellow rims remained stable in the presence of high genetic divergence among populations. We therefore suggest that how predators learn warning signals may cause stabilizing selection on individual colour pattern elements, and will thus have important implications on the evolution of warning signals.
Involvement of Microphthalmia in the Inhibition of Melanocyte Lineage Differentiation and of Melanogenesis by Agouti Signal Protein*

In mouse follicular melanocytes, production of eumelanins (brown-black pigments) and pheomelanins (yellow-brownish pigments) is under the control of two intercellular signaling molecules that exert opposite actions, α-melanocyte-stimulating hormone (αMSH) which preferentially increases the synthesis of eumelanins, and agouti signal protein (ASP) whose expression favors the production of hair containing pheomelanins. In this study, we report that ASP does not only affect mature melanocytes but can also inhibit the differentiation of melanoblasts. We show that both αMSH and forskolin promote the differentiation of murine melanoblasts into mature melanocytes and that ASP inhibits this process. We present evidence that the expression of a specific melanogenic transcription factor, microphthalmia, and its binding to an M box regulatory element, is inhibited by ASP. We also show that, in B16 murine melanoma cells, ASP inhibits αMSH-stimulated expression of tyrosinase, tyrosine-related proteins 1 and 2 through an inhibition of the transcription activity of their respective promoters. Further, ASP inhibits αMSH-induced expression of the microphthalmia gene and reduces the level of microphthalmia in the cells. Our data demonstrate that ASP can regulate both melanoblast differentiation and melanogenesis, pointing out the key role of microphthalmia in the control of these processes.
Mouse Anesthesia and Analgesia

Providing anesthesia and analgesia for mouse subjects is a common and critical practice in the laboratory setting. These practices are necessary for performing invasive procedures, achieving prolonged immobility for sensitive imaging modalities (magnetic resonance imaging for instance), and providing intra‐ and post‐procedural pain relief. In addition to facilitating the procedures performed by the investigator, the provision of anesthesia and analgesia is crucial for the preservation of animal welfare and for humane treatment of animals used in research. Furthermore, anesthesia and analgesia are important components of animal use protocols reviewed by Institutional Animal Care and Use Committees, requiring careful consideration and planning for the particular animal model. In this article, we provide technical outlines for the investigator covering the provision of anesthesia by two routes (injectable and inhalant), guidelines for monitoring anesthesia, current techniques for recognition of pain, and considerations for administering preventative analgesia. © 2015 by John Wiley & Sons, Inc.