Miracle-dz/UniFAR-FTUs huggingface dataset:
Human Cytomegalovirus Major Immediate Early 1 Protein Targets Host Chromosomes by Docking to the Acidic Pocket on the Nucleosome Surface

ABSTRACT The 72-kDa immediate early 1 (IE1) protein encoded by human cytomegalovirus (hCMV) is a nuclearly localized promiscuous regulator of viral and cellular transcription. IE1 has long been known to associate with host mitotic chromatin, yet the mechanisms underlying this interaction have not been specified. In this study, we identify the cellular chromosome receptor for IE1. We demonstrate that the viral protein targets human nucleosomes by directly binding to core histones in a nucleic acid-independent manner. IE1 exhibits two separable histone-interacting regions with differential binding specificities for H2A-H2B and H3-H4. The H2A-H2B binding region was mapped to an evolutionarily conserved 10-amino-acid motif within the chromatin-tethering domain (CTD) of IE1. Results from experimental approaches combined with molecular modeling indicate that the IE1 CTD adopts a β-hairpin structure, docking with the acidic pocket formed by H2A-H2B on the nucleosome surface. IE1 binds to the acidic pocket in a way similar to that of the latency-associated nuclear antigen (LANA) of the Kaposi's sarcoma-associated herpesvirus. Consequently, the IE1 and LANA CTDs compete for binding to nucleosome cores and chromatin. Our work elucidates in detail how a key viral regulator is anchored to human chromosomes and identifies the nucleosomal acidic pocket as a joint target of proteins from distantly related viruses. Based on the striking similarities between the IE1 and LANA CTDs and the fact that nucleosome targeting by IE1 is dispensable for productive replication even in “clinical” strains of hCMV, we speculate that the two viral proteins may serve analogous functions during latency of their respective viruses.
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The nature of the recently discovered color-induced nasal thermal sensations was investigated in four Experiments. Subjects were required to fixate a bottle containing a red or green solution presented centrally (Exp1 and Exp4) or laterally (Exp2) and to sniff another bottle, always the same one, but which they were not allowed to see, containing 10 ml of a colorless, odorless and trigeminal-free solution. Each nostril was tested separately, and subjects were asked whether the sniffed solution induced warming or cooling sensations (plus an ambient sensation in Exp4) in the nasal cavity. The results of Experiments 1 and 2 confirmed the warming/left nostril–cooling/right nostril dissociation, suggesting the existence of different lateralized processes for thermal processing. However, Experiment 2 failed to demonstrate dominance of warming responses when subjects’ eyes were directed to the left or cooling responses when they were directed to the right. Nor did gaze direction interact with the tested nostril. This suggests that the color-induced thermal sensations are specifically related to the nasal trigeminal system, rather than a general process related to general hemispheric activity. When the exposed bottles were colorless (Exp3), no lateralized patterns were observed, suggesting, in combination with the results of Experiments 1 and 2, that both color cues and nasal stimulations are necessary for lateralized patterns to arise. Rendering the temperature judgment even more difficult (Exp4), made the lateralized patterns shift towards the associated (i.e., ambient) responses. The results are discussed in a general framework which considers that, even in the absence of real thermal stimulus, preparing to process thermal stimuli in the nasal cavity may activate the underlying lateralized neural mechanisms, and that those mechanisms are reflected in
Improving the quality of life of patients with prostate carcinoma

Treatments for clinically localized prostate carcinoma are accompanied by sexual, urinary, and bowel dysfunction and other sequelae that can result in significant distress and reduced well being. Methods capable of improving quality of life are needed that can be integrated into clinical practice. To address this need, a nurse‐driven, cancer care intervention was developed and tested.
Temporal processing and speech recognition in cochlear implant users

Although the speech recognition performance of cochlear implant patients has steadily improved in recent years, considerable variability remains in implant patient outcomes. Here, we report on a correlation between cochlear implant patients' auditory temporal processing and speech recognition abilities. Modulation detection thresholds were measured as a function of stimulation level; phoneme recognition was also assessed. Results showed marked individual differences in the shape and absolute sensitivity of subjects' modulation threshold functions. Statistical analysis revealed a strong correlation between phoneme recognition scores and subjects' mean modulation thresholds, demonstrating the contribution of temporal processing to implant speech perception. In correlating a basic psychophysical measure to speech performance, these results should contribute toward improved speech processor design and rehabilitation tools for cochlear implant patients.
Regulation of proliferation of the fetal myocardium

Growth of the myocardium involves the completion of a fixed number of rounds of cell division during the embryonic and fetal stages followed by entry into a postmitotic state and hypertrophy of the postmitotic cardiomyocytes during the later stages of heart growth. It has been suggested that at the time of its determination in the early embryo, the embryonic myocardium is programmed for a fixed and limited number of cell divisions, after which the transition to the postmitotic state occurs autonomously. The proliferative response of cultured myocardium of the fetal chick was explored in four culture settings: monolayer cell culture, collagen lattice culture, organ culture of reaggregated cardiomyocyte tissue (cardiomyocyte spheroid culture), and organ culture of pieces of the ventricle wall. Several growth factors were identified by their ability to stimulate DNA synthesis in cardiomyocytes, identified by the incorporation of 5‐bromodeoxyuridine (BrdU). The serine proteases thrombin and trypsin, fibroblast growth factor‐2 (FGF‐2), transforming growth factor‐α (TGF‐α), and insulin‐like growth factor‐II (IGF‐II) all show growth factor activity but only for cardiomyocytes cultured in three‐dimensional myocardial tissue, and not for cardiomyocytes maintained in monolayer cell culture. Thus, during its proliferation phase, the growth of the fetal myocardium is not controlled solely by internal, cell‐autonomous programs, but is subject to external regulation by a family of peptide growth factors. The unconventional setting of three‐dimensional culture of the myocardium is required to demonstrate its responsiveness to growth factor challenge. © 2000 Wiley‐Liss, Inc.
INFLUENCE OF HIGH‐INTENSITY INTERVAL TRAINING ON ADAPTATIONS IN WELL‐TRAINED CYCLISTS

The purpose of the present study was to examine the influence of 3 different high-intensity interval training regimens on the first and second ventilatory thresholds (VT1 and VT2), anaerobic capacity (ANC), and plasma volume (PV) in well-trained endurance cyclists. Before and after 2 and 4 weeks of training, 38 well-trained cyclists (VO2peak = 64.5 ± 5.2 ml·kg-1·min-1) performed (a) a progressive cycle test to measure VO2peak, peak power output (PPO), VT1, and VT2; (b) a time to exhaustion test (Tmax) at their VO2peak power output (Pmax); and (c) a 40-km time-trial (TT40). Subjects were assigned to 1 of 4 training groups (group 1: n = 8, 8 3 60% Tmax at Pmax, 1:2 work-recovery ratio; group 2: n = 9, 8 × 60% Tmax at Pmax, recovery at 65% maximum heart rate; group 3: n = 10, 12 × 30 seconds at 175% PPO, 4.5-minute recovery; control group: n = 11). The TT40 performance, VO2peak, VT1,VT2, and ANC were all significantly increased in groups 1, 2, and 3 (p < 0.05) but not in the control group. However, PV did not change in response to the 4-week training program. Changes in TT40 performance were modestly related to the changes in VO2peak, VT1, VT2, and ANC (r = 0.41, 0.34, 0.42, and 0.40, respectively; all p < 0.05). In conclusion, the improvements in TT40 performance were related to significant increases in VO2peak, VT1,VT2, and ANC but were not accompanied by significant changes in PV. Thus, peripheral adaptations rather than central adaptations are likely responsible for the improved performances witnessed in well-trained endurance athletes following various forms of high-intensity interval training programs.
HIV-1 Nef Triggers Macrophage Fusion in a p61Hck- and Protease-Dependent Manner

Macrophages are a major target of HIV-1 infection. HIV-1–infected macrophages form multinucleated giant cells (MGCs) using poorly elucidated mechanisms. In this study, we show that MGC formation was reduced when human macrophages were infected with nef-deleted HIV-1. Moreover, expression of Nef, an HIV-1 protein required in several aspects of AIDS, was sufficient to trigger the formation of MGCs in RAW264.7 macrophages. Among Nef molecular determinants, myristoylation was dispensable, whereas the polyproline motif was instrumental for this phenomenon. Nef has been shown to activate hematopoietic cell kinase (Hck), a Src tyrosine kinase specifically expressed in phagocytes, through a well-described polyproline–SH3 interaction. Knockdown approaches showed that Hck is involved in Nef-induced MGC formation. Hck is expressed as two isoforms located in distinct subcellular compartments. Although both isoforms were activated by Nef, only p61Hck mediated the effect of Nef on macrophage fusion. This process was abolished in the presence of a p61Hck kinase-dead mutant or when p61Hck was redirected from the lysosome membrane to the cytosol. Finally, lysosomal proteins including vacuolar adenosine triphosphatase and proteases participated in Nef-induced giant macrophage formation. We conclude that Nef participates in HIV-1–induced MGC formation via a p61Hck- and lysosomal enzyme-dependent pathway. This work identifies for the first time actors of HIV-1–induced macrophage fusion, leading to the formation of MGCs commonly found in several organs of AIDS patients.
Evaluation of variable mandibular advancement appliance for treatment of snoring and sleep apnea.

OBJECTIVE To evaluate an adjustable mandibular positioning appliance for treatment of snoring and sleep apnea. METHODS One hundred thirty-four patients with baseline apnea/hypopnea index (AHI) of 37 +/- 28 events/h (mean +/- SD) received the appliance. The efficacy of the appliance was assessed by the following investigations, performed at baseline and with the appliance: polysomnography, Epworth sleepiness scale, bedpartners' assessment of snoring severity, patients' assessment of side effects, and overall satisfaction. RESULTS Thirteen patients were lost to follow-up. An additional 46 patients had no follow-up polysomnography, but answered the questionnaires. A total of 75 patients had polysomnography at baseline and with the appliance. We found a significant reduction in AHI from 44 +/- 28 events/h to 12 +/- 15 events/h (p < 0.0005) and a reduction in the arousal index from 37 +/- 27 events/h to 16 +/- 13 events/h (p < 0.05). Epworth scores fell from 11 +/- 5 to 7 +/- 3 (p < 0.0005). Bedpartners' assessment revealed marked improvement in snoring. For example, at baseline 96% of patients were judged to snore loudly "often" or "always" by their bedpartners, whereas only 2% were judged so while using dental appliance. The most frequent side effect was teeth discomfort, present "sometimes" or "often" in up to 32% of patients. Follow-up clinical assessment in 121 patients conducted on the average 350 days after the insertion of the appliance revealed that 86% of patients continued to use the appliance nightly; 60% were very satisfied with the appliance, 27% were moderately satisfied, 11% were moderately dissatisfied, and 2% were very dissatisfied. CONCLUSION We conclude that the adjustable mandibular positioning appliance is an effective treatment alternative for some patients with snoring and sleep apnea.
Design and Implementation of 24 GHz Multichannel FMCW Surveillance Radar with a Software-Reconfigurable Baseband

We designed and developed a 24 GHz surveillance FMCW (Frequency Modulated Continuous Wave) radar with a software-reconfigurable baseband. The developed radar system consists of transceiver, two selectable transmit antennas, eight parallel receive antennas, and a back-end module for data logging and to control the transceiver. The architecture of the developed radar system can support various waveforms, gain control of receive amplifiers, and allow the selection of two transmit antennas. To do this, we implemented the transceiver using a frequency synthesizer device and a two-step VGA (Variable Gain Amplifier) along with switch-controlled transmit antennas. To support high speed implementation features along with good flexibility, we developed a back-end module based on a FPGA (Field Programmable Gate Array) with a parallel architecture for the real-time data logging of the beat signals received from a multichannel 24 GHz transceiver. To verify the feasibility of the developed radar system, signal processing algorithms were implemented on a host PC. All measurements were carried out in an anechoic chamber to extract a 3D range-Doppler-angle map and target detections. We expect that the developed software-reconfigurable radar system will be useful in various surveillance applications.
A longitudinal study of the vaginal flora over a menstrual cycle

Healthy female volunteers participated in an anonymous study to monitor vaginal flora by taking daily vaginal samples and making a smear for later Gram-staining, as well as recording information on genital symptoms, sexual activity, contraceptive and bathing practices. A modification of Spiegel's criteria was used to categorize the Gram-stained smears, an intermediate category between normal flora and bacterial vaginosis (BV) being recognized. Of the 22 volunteers who completed the study, one was excluded because of pregnancy. Of the remaining 21 women, 10 (48%) had a normal flora throughout the study, 4 (19%) had an abnormal flora throughout and 7 (33%) had a basically normal flora which underwent a change to either an intermediate flora in 5 women or fully developed BV in 2 of them. In 5 (71%) of these women the change occurred within the first 9 days of the cycle. Transient changes in the vaginal microbial flora occurred predominantly in the first part of the menstrual cycle which suggests that in some women hormonal changes could have a role in the pathogenesis of bacterial vaginosis.
The preproghrelin 3056 TT genotype is associated with the feeling of hunger and low acylated ghrelin levels in Japanese patients with Helicobacter pylori-negative functional dyspepsia.

OBJECTIVE An impairment of gastric motility is strongly associated with the pathophysiology of functional dyspepsia (FD). Plasma ghrelin is one of the key molecules linked to gastric motility. Therefore, this study aimed to evaluate whether ghrelin (GHRL) gene polymorphisms are associated with clinical symptoms, the plasma ghrelin levels and gastric emptying in patients with FD as defined by the Rome III classification. METHODS We enrolled 74 Helicobacter pylori-negative patients presenting with typical symptoms of FD (epigastric pain syndrome (EPS), n=23; postprandial distress syndrome (PDS), n=51) and 102 healthy volunteers. Gastric motility was evaluated according to the Tmax value and T1/2 using the (13)C-acetate breath test. We used the Rome III criteria to evaluate upper abdominal symptoms and SRQ-D scores to determine the depression status. The Arg51Gln(346G->A), preproghrelin3056T->C, Leu72Met(408C->A) and Gln90Leu(3412T->A) polymorphisms were analyzed in DNA in blood samples obtained from the enrolled subjects. Genotyping was performed using polymerase chain reaction. RESULTS There was a significant relationship (p=0.048) between the preproghrelin 3056TT genotype and the serum levels of acylated ghrelin in the H. pylori-negative FD patients. The preproghrelin 3056TT genotype was significantly (p=0.047) associated with the feeling of hunger in the H. pylori-negative FD patients. CONCLUSION The preproghrelin 3056TT genotype is significantly associated with the acylated ghrelin levels and the feeling of hunger in H. pylori-negative FD patients. Further studies are needed to clarify the association between the preproghrelin 3056TT genotype and lower plasma acylated ghrelin levels and the impact of this relationship on the feeling of hunger in H. pylori-negative FD patients.
TIMP4 expression is regulated by miR‐200b‐3p in prostate cancer cells

In prostate cancer TIMP4 expression level fluctuates with tumor progression. The mechanism and factors influencing its expression remain unclear. The aim of the study was to test the hypothesis on regulation of TIMP4 by microRNA‐200b‐3p. The levels of TIMP4 and miR‐200b‐3p expression were determined by real time PCR in 27 prostate carcinomas and eight benign prostatic hyperplasia samples. We found that miR‐200b‐3p positively correlated with TIMP4 expression in cancer samples (r = 0.46; p < 0.02). Moreover, mean miR‐200b‐3p level and TIMP4 expression were both higher in cancer tissues compared to benign prostatic hyperplasia samples (p > 0.05). Next, to test probable mechanisms of the regulation androgen‐sensitive human prostate adenocarcinoma cells (LNCaP) were transfected with synthetic‐miR‐200b‐3p or its synthetic antagonist. Modulation of miR‐200b‐3p in LNCaP cells had an impact on TIMP4 expression confirming the observation made in analyzed clinical samples. Two targets of miR‐200b‐3p: ZEB1 and ETS1 were investigated subsequently as potential regulators of TIMP4, however, no effect of their modulation on TIMP4 expression in LNCaP cells was found. Concluding, miR‐200b‐3p mediates regulation of TIMP4 expression in prostate cancer but exact mechanism needs to be investigated.
A meta-regression of the long-term effects of deep brain stimulation on balance and gait in PD

Objective: Deep brain stimulation (DBS) alleviates the cardinal Parkinson disease (PD) symptoms of tremor, rigidity, and bradykinesia. However, its effects on postural instability and gait disability (PIGD) are uncertain. Contradictory findings may be due to differences the in stimulation site and the length of time since DBS surgery. This prompted us to conduct the first meta-regression of long-term studies of bilateral DBS in the subthalamic nucleus (STN) and globus pallidus interna (GPi). Results: Eleven articles reported a breakdown of the Unified Parkinson's Disease Rating Scale score before and beyond 3 years postsurgery (mean 4.5 years). Random effects meta-regression revealed that DBS initially improved PIGD compared to the OFF medicated state before surgery, but performance declined over time and extrapolation showed subjects would reach presurgery levels 9 years postsurgery. ON medication, DBS improved PIGD over and above the effect of medication before surgery. Nevertheless, for the STN group, PIGD progressively declined and was worse than presurgery function within 2 years. In contrast, GPi patients showed no significant long-term decline in PIGD in the medicated state. Improvements in cardinal signs with DBS at both sites were maintained across 5 years in the OFF and ON medication states. Conclusions: DBS alone does not offer the same improvement to PIGD as it does to the cardinal symptoms, suggesting axial and distal control are differentially affected by DBS. GPi DBS in combination with levodopa seemed to preserve PIGD better than did STN DBS, although more studies of GPi DBS and randomized controls are needed.
Melnikov Chaos in a Modified Rayleigh-Duffing Oscillator with ϕ6 Potential

The chaotic behavior of the modified Rayleigh–Duffing oscillator with ϕ6 potential and external excitation is investigated both analytically and numerically. The so-called oscillator models, for example, ship rolling motions. The single well and triple well potential cases are considered. Melnikov method is applied and the conditions for the existence of homoclinic and heteroclinic chaos are obtained. The effects of nonlinear damping on roll motion of ships are analyzed in detail. As it is known, nonlinear roll damping is a very important parameter in estimating ship responses. It is noted that the pure and unpure quadratic damping parameters affect the Melnikov criterion in the heteroclinic and homoclinic cases respectively while the pure cubic parameter affects the amplitude in both cases. The predictions have been tested with numerical simulations based on the basin of attraction. It is pointed out that certain quadratic damping effects are contrary to cubic damping effect.
Bimanual Handedness in Adults Who Stutter

25 adult stutterers and 29 nonstutterers who were right-handed as defined by a positive Laterality Quotient on the Edinburgh Handedness Inventory were compared with respect to their pattern of hand use in performing seven common tasks that involve bimanual cooperation. Among the stutterers was a higher proportion of participants who showed anomalies in how they carried out the two tasks that required synchronous manipulation by the two hands. On two other tasks that required speeded performance, the groups were similar in dealing playing cards with the right or left hands, but the stutterers were slower than nonstutterers and did not show a right-hand advantage on a task requiring removal of a nut from a bolt. The results were interpreted as indicating difficulty by stutterers in carrying out synchronously different response elements of motoric tasks.
A New Stilbene Dimer – Shegansu B from Belamcanda chinensis

Abstract A new dimeric stilbene, named shegansu B (1) was isolated from the ethanolic extract of the roots of Belamcanda chinensis (L.) DC. , along with the known compounds isorhapontigenin, resveratol, p-hydroxybenzoic acid, iridin, tectoridin, tectorigenin and daucosterol. The structures were elucidated by means of spectroscopic evidence including 2D-NMR studies.
Failure to Learn from Repeated Mistakes: Persistent Decision-Making Impairment as Measured by the Iowa Gambling Task in Patients with Ventromedial Prefrontal Cortex Lesions

Abstract Although frontal patients show impaired decision-making on the Iowa Gambling Task (IGT), there has been no follow-up study to date to determine whether there is recovery of function over time. We examined neurological participants’ performance on repeated administrations of the IGT over the course of 6 years. We found that, while non-neurological participants showed considerable improvement due to practice effects on the IGT, patients with ventromedial prefrontal cortex (VMPFC) damage persisted in showing impaired performance on each retest. These results validate the clinical observations that VMPFC dysfunction does not appear to be subject to autonomous recovery over time in real-life. (JINS, 2012, 18, 1–4)