Miracle-dz/UniFAR-FTUs huggingface dataset:
Nuclear RNA Is Extruded from Apoptotic Cells

During spontaneous apoptosis of thymocytes there is extrusion of ribonucleoproteins (RNPs) from the cell. The aim of this investigation was to elucidate whether the RNP aggregates in apoptotic cells and bodies still contain RNA in an appreciable amount. We demonstrated by specific cytochemical techniques that the aggregates of nuclear RNPs extruded in the cytoplasm of spontaneously apoptotic thymocytes contain RNA in a sufficient amount to be detected cytochemically. These heterogeneous ectopic RNP-derived structures (HERDS) are formed by perichromatin fibrils, interchromatin granules, perichromatin granules, and nucleolar material. The RNA detected inside these clusters should therefore correspond to both mRNA and snRNA as well as to rRNA. We never observed DNA-contaning aggregates in the cytoplasm of apoptotic thymocytes. The presence of RNA in the HERDS that may be released from apoptotic cells suggests that the decrease in the amount of total RNA during apoptosis may be mostly linked to cellular extrusion rather than to degradation of RNA by RNase activities. Another interesting aspect of these results lies in the hypothesis of apoptosis as a possible cause for the presence of autoantibodies in the serum of patients with systemic autoimmune diseases.
A 16 W Balanced Intensity Dual-Frequency Laser With 53 GHz Frequency Separation

A 16.1 W continuous-wave balanced intensity dual-frequency laser based on an YVO4 microchip seed laser, together with a two-stage laser amplifier, was demonstrated. In order to obtain such a high-power dual-frequency laser as well as a balanced intensity distribution of the dual-mode, the seed laser wavelength was precisely tuned to spectrally match with the gain curve of the amplifier by employing a temperature controller. Finally, when the heat sink temperature of the amplifier crystal was kept at 30.0 °C, the dual-mode seed laser operated at 16.0 °C was amplified from 284.5 mW to 16.1 W with a balanced intensity distribution, and frequency separation was measured as 53.2 GHz.
DNA sequences involved in transcriptional regulation of the mouse beta-globin promoter in murine erythroleukemia cells

We have developed a transient assay in murine erythroleukemia (MEL) cells to analyze the cis-acting sequence requirements for transcriptional regulation of the mouse beta-major-globin promoter. From deletion analysis, a fragment of the promoter region, from -106 to +26 relative to the RNA cap site, was found to be sufficient for regulated transcription in MEL cells following induction of differentiation by dimethyl sulfoxide. Single-base mutational analysis of this 132-base-pair promoter fragment identified three sequence elements required for transcription in MEL cells. These are the ATATAA sequence at -31 to -26, the CCAATC sequence between -77 and -72, and the GCCACACCC sequence between -95 and -87. In addition, we found a requirement for sequences adjacent to the CCAAT and ATATAA consensus motifs. Point mutations within the promoter did not abolish transcriptional regulation following induction of differentiation by dimethyl sulfoxide. However, mutations that resulted in reduced transcription levels in uninduced MEL cells gave similarly decreased levels in induced MEL cells.
Work Retention and Nonspecific Low Back Pain

Study Design. A cohort study of patients with nonspecific low back pain (LBP) participated in a 4-week multidisciplinary rehabilitation program. Objective. To identify factors that predict work retention 24 months after treatment in patients with nonspecific LBP. Summary of Background Data. There is evidence that select physical, psychologic, and psychosocial factors are related to positive outcome for work-related nonspecific LBP. However, there is very little information related to work retention following an episode of nonspecific LBP. This is an exploratory study to identify select physical and psychosocial factors related to work retention. Methods. Patients who returned to work after treatment (n = 67) were followed for 2 years. Physical baseline measures included tests of flexibility, strength, and functional capacity. Psychosocial baseline measures were The Symptoms Checklist 90-R, The Pain Beliefs and Perceptions Inventory, The Oswestry Scale of perceived disability, The Work Stress Inventory, and The Quality of Life Scale. All physical parameters, perceived disability, and quality of life were tested before and after treatment. The dependent variable, work retention, was defined as the number of days that the subject worked during the 2-year follow-up period. Survival analysis was used to establish the predictive model. Result. The average time out of work before treatment was 9 months (standard deviation 12.8) for 67 subjects (mean age 40 years [standard deviation 9.6]), including 18 females and 49 males. There were 18 participants (25%) that had interruption of work retention at follow-up. Average work retention was 362 days (range 47–682). Variables that reached a P value of <0.10 in the bivariate analysis were included in the multivariate analysis. They were trunk flexion (hazard ratio [HR = 2.4], 95% confidence interval [CI] 1.24–4.38; P = 0.01), trunk extension (HR = 2.1, 95% CI 1.02–4.16; P = 0.04), the somatization scale from the Symptom Checklist 90 revised (HR = 2.0, 95% CI 1.03–4.05; P = 0.04), and the obsessive-compulsiveness scale from the Symptom Checklist 90 revised (HR = 0.4, 95% CI 0.12–1.15; P = 0.09). Results showed that post-test trunk flexion, somatization, and obsessive compulsiveness predicted work retention (final trunk flexion HR = 2.5 [95% CI 1.26–4.79; P = 0.01], somatization scale HR = 2.5 [95% CI 1.25–4.93; P = 0.01], and obsessive compulsion HR = 0.2 [95% CI 0.07–0.77; P = 0.02]). Conclusion. Psychosocial and physical factors are associated with work retention for patients with nonspecific LBP. The predictive value of certain constructs may vary with the time when they are assessed and how outcome is operationalized. Further studies are needed to confirm these findings.
The effect of Nesfatin-1 on heart L-type Ca²⁺ channel α1c subunit in rats subjected to chronic restraint stress.

BACKGROUND Elevated L-type Ca²⁺channel expression level increases Ca²⁺ influx. This can cause hypertrophy and pathological remodeling of the heart especially under stress conditions. Nesfatin-1 can activate hypothalamic L, P and Q type Ca²⁺ channels and increase insulin secretion in pancreatic islet beta cells via activation of L-type Ca²⁺ channels. On the other hand, the effect of nesfatin-1 on cardiac L-type Ca²⁺ channels has not been studied yet. OBJECTIVES We aimed to identify the effect of peripheral chronic Nesfatin-1 application on cardiac L-type Ca²⁺ channel α1c subunit expression level in normal rats and those subjected to chronic restraint stress. METHODS Three-month aged Wistar albino rats were randomly divided into 4 groups (n = 7) as Control, Stress, Control+Nesfatin-1, and Nesfatin-1+Stress. Rats in groups subjected to restraint stress were placed in a specially built size-manipulable cabin for 2 h/day (between 10:00 and 12:00 a.m.) for 10 consecutive days without allowing water and food intake. Nesfatin-1 segment (0.25 nmol/g bw intraperitoneally) was applied during the 10 consecutive days. Western blot analyses were performed to determine the expression level of L-type Ca²⁺ channel α1c subunit protein in rat cardiac extracts. RESULTS Cardiac L-type Ca²⁺ channel α1c subunit protein expression levels were increased significantly after chronic peripheral Nesfatin-1 application in rats subjected to restraint stress (p = 0.032). CONCLUSION We can conclude that Nesfatin-1 can cause cardiac failures during clinical treatments by elevating cardiac L-type Ca²⁺ channel α1c subunit protein expression level (Fig. 2, Ref. 26).
Aminopeptidase N (CD13) functionally interacts with FcγRs in human monocytes

Aminopeptidase N (E.C. 3.4.11.2) is a membrane‐bound metalloproteinase expressed in many tissues. Although its cytoplasmic portion has only eight amino acids, cross‐linking of CD13 by monoclonal antibodies (mAb) has been shown to trigger intracellular signaling. A functional association between CD13 and receptors for immunoglobulin G (FcγRs) has been proposed. In this work, we evaluated possible functional interactions between CD13 and FcγRs in human peripheral blood monocytes and in U‐937 promonocytic cells. Our results show that during FcγR‐mediated phagocytosis, CD13 redistributes to the phagocytic cup and is internalized into the phagosomes. Moreover, modified erythrocytes that interact with the monocytic cell membrane through FcγRI and CD13 are ingested simultaneously, more efficiently than those that interact through the FcγRI only. Also, co‐cross‐linking of CD13 with FcγRI by specific mAbs increases the level and duration of Syk phosphorylation induced by FcγRI cross‐linking. Finally, FcγRI and CD13 colocalize in zones of cellular polarization and coredistribute after aggregation of either of them. These results demonstrate that CD13 and FcγRI can functionally interact on the monocytic cell membrane and suggest that CD13 may act as a signal regulator of FcγR function.
Second malignancies in children with neuroblastoma after combined treatment with 131I‐metaiodobenzylguanidine

131I‐metaiodobenzylguanidine (131I‐MIBG) is selectively taken up by cells of neural crest origin, allowing targeted radiotherapy of tumors such as neuroblastoma (NB) and pheochromocytoma. Radiotherapy may provide additional benefits in the treatment of NB, with moderate side effects such as hematologic and thyroid toxicity. However, with longer follow‐up, other complications might occur. We describe our experience with second cancers occurring in children treated with 131I‐MIBG and chemotherapy.
The Recognition Of Partially Occluded Objects with Support Vector Machines, Convolutional Neural Networks and Deep Belief Networks

Abstract Biologically inspired artificial neural networks have been widely used for machine learning tasks such as object recognition. Deep architectures, such as the Convolutional Neural Network, and the Deep Belief Network have recently been implemented successfully for object recognition tasks. We conduct experiments to test the hypothesis that certain primarily generative models such as the Deep Belief Network should perform better on the occluded object recognition task than purely discriminative models such as Convolutional Neural Networks and Support Vector Machines. When the generative models are run in a partially discriminative manner, the data does not support the hypothesis. It is also found that the implementation of Gaussian visible units in a Deep Belief Network trained on occluded image data allows it to also learn to effectively classify non-occluded images
Sequence‐selective DNA binding drugs mithramycin A and chromomycin A3 are potent inhibitors of neuronal apoptosis induced by oxidative stress and DNA damage in cortical neurons

Global inhibitors of RNA or protein synthesis such as actinomycin D or cycloheximide abrogate neuronal apoptosis induced by numerous pathological stimuli in vitro and in vivo. The clinical application of actinomycin D or cycloheximide to human neurological disease has been limited by the toxicities of these agents. To overcome these toxicities, strategies must be developed to inhibit selectively the expression of deleterious proapoptotic proteins, while leaving the expression of antiapoptotic, proregeneration, and other critical homeostatic proteins unperturbed. Mithramycin A (trade name Plicamycin) is an aureolic acid antibiotic that has been used in humans to treat hypercalcemia and several types of cancers. This class of agents is believed to act, in part, by selectively inhibiting gene expression by displacing transcriptional activators that bind to G‐C‐rich regions of promoters. Here we demonstrate that mithramycin A and its structural analog chromomycin A3 are potent inhibitors of neuronal apoptosis induced by glutathione depletion‐induced oxidative stress or the DNA‐damaging agent camptothecin. We correlate the protective effects of mithramycin A with its ability to inhibit enhanced DNA binding of the transcription factors Sp1 and Sp3 to their cognate “G‐C” box induced by oxidative stress or DNA damage. The protective effects of mithramycin A cannot be attributed to global inhibition of protein synthesis. Together, these results suggest that mithramycin A and its structural analogs may be effective agents for the treatment of neurological diseases associated with aberrant activation of apoptosis and highlight the potential use of sequence‐selective DNA‐binding drugs as neurological therapeutics. Ann Neurol 2001;49:345–354
Are Some Anticoagulants More Equal Than Others? - Evaluating the Role of Novel Oral Anticoagulants in AF Ablation

Left atrial ablation strategies are being increasingly performed as a Class 1 therapeutic indication for drug refractory paroxysmal atrial fibrillation (AF). Traditionally AF ablation has been performed with patients on uninterrupted warfarin therapy, however over the last few years, novel oral anticoagulants (NOACs) have emerged as attractive alternatives to warfarin in order to reduce stroke risk due to AF. NOACs are therefore increasingly being used instead of warfarin in the management of AF. There is also mounting evidence mainly in the form of small randomised studies and meta-analysis that have demonstrated that the use of NOACs for AF ablation is efficacious, safe and convenient. However the peri-procedural dosing protocols used in various studies especially in terms of whether NOAC use is interrupted or uninterrupted during AF ablation, have significant inter-operator and inter-institution variability. Currently there is also a lack of randomised controlled trials to validate the data obtained from meta-analyses. There is also evidence that use of NOACs may increase the requirement of unfractionated heparin during the procedure. This review article shall examine the currently available evidence-base, appraise the gaps in the current evidence and also underscore the need for larger randomised clinical trials in this rapidly developing field.
GDNF is an endogenous negative regulator of ethanol-mediated reward and of ethanol consumption after a period of abstinence.

BACKGROUND We previously found that activation of the glial cell line-derived neurotrophic factor (GDNF) pathway in the ventral tegmental area (VTA) reduces ethanol-drinking behaviors. In this study, we set out to assess the contribution of endogenous GDNF or its receptor GFRalpha1 to the regulation of ethanol-related behaviors. METHODS GDNF and GFRalpha1 heterozygote mice (HET) and their wild-type littermate controls (WT) were used for the studies. Ethanol-induced hyperlocomotion, sensitization, and conditioned place preference (CPP), as well as ethanol consumption before and after a period of abstinence were evaluated. Blood ethanol concentration (BEC) was also measured. RESULTS We observed no differences between the GDNF HET and WT mice in the level of locomotor activity or in sensitization to ethanol-induced hyperlocomotion after systemic injection of a nonhypnotic dose of ethanol and in BEC. However, GDNF and GFRalpha1 mice exhibited increased place preference to ethanol as compared with their WT littermates. The levels of voluntary ethanol or quinine consumption were similar in the GDNF HET and WT mice, however, a small but significant increase in saccharin intake was observed in the GDNF HET mice. No changes were detected in voluntary ethanol, saccharin or quinine consumption of GFRalpha1 HET mice as compared with their WT littermates. Interestingly, however, both the GDNF and GFRalpha1 HET mice consumed much larger quantities of ethanol after a period of abstinence from ethanol as compared with their WT littermates. Furthermore, the increase in ethanol consumption after abstinence was found to be specific for ethanol as similar levels of saccharin intake were measured in the GDNF and GFRalpha1 HET and WT mice after abstinence. CONCLUSIONS Our results suggest that endogenous GDNF negatively regulates the rewarding effect of ethanol and ethanol-drinking behaviors after a period of abstinence.
Choline Induces Transcriptional Repression and Proteasomal Degradation of the Malarial Phosphoethanolamine Methyltransferase

ABSTRACT During its intraerythrocytic life cycle, the malaria parasite Plasmodium falciparum undergoes dramatic metabolic and morphological changes and multiplies to produce up to 36 new daughter parasites. This rapid multiplication of the parasite requires an active synthesis of new membranes. The major component of these membranes, phosphatidylcholine, is synthesized via two metabolic routes, the CDP-choline pathway, which uses host choline as a precursor, and the plant-like serine decarboxylase-phosphoethanolamine methyltransferase (SDPM) pathway, which uses host serine as a precursor. Here we provide evidence indicating that the activity of the SDPM pathway is regulated by the CDP-choline precursor, choline. We show that the phosphoethanolamine methyltransferase, Pfpmt, a critical enzyme in the SDPM pathway, is down-regulated at the transcriptional level as well as targeted for degradation by the proteasome in the presence of choline. Transcript analysis revealed that PfPMT transcription is repressed by choline in a dose-dependent manner. Immunoblotting, pulse-chase experiments, and immunoprecipitation studies demonstrated that Pfpmt degradation occurs not only in wild-type but also in transgenic parasites constitutively expressing Pfpmt. The proteasome inhibitor bortezomib inhibited choline-mediated Pfpmt degradation. These data provide the first evidence for metabolite-mediated transcriptional and proteasomal regulation in Plasmodium and will set the stage for the use of this system for conditional gene and protein expression in this organism.
On the Accuracy of History, Physical Examination, and Erythrocyte Sedimentation Rate in Diagnosing Low Back Pain in General Practice: A Criteria‐Based Review of the Literature

Study Design A criteria-based review of the literature was conducted regarding the accuracy of history, physical examination, and erythrocyte sedimentation rate in diagnosing low back pain. Objectives. To perform meta-analysis of the literature regarding signs and symptoms in diagnosing radiculopathy, ankylosing spondylitis, and verterbral cancer. Summary of Background Data Diagnosing low back pain, especially in general practice, depends largerly on history taking, physical examination, and the erythrocyte sedimentation rate. No previous review has assessed the diagnostic accuracy of signs and symptoms in a systematic way, taking into account the methodological quality of studies. Methods The literature was reviewed for relevant studies. Retrieved studies were independently rated for methodological quality by two reviewers. The reported sensitivity and specificity in the rated studies were reviewed. Results Thirty-six eligible studies were retrieved. Major methodological shortcomings were observed, and only 19 studies scored ±55 points (maximal score 100). Not one single test appeared to have high sensitivity and high specificity in radiculopathy. The combined history and the erythrocyte sedimentation rate had relatively high diagnostic accuracy in vertebral cancer, Getting out of bed at night and reduced lateral mobility seemed to be the only moderately accurate items in ankylosing spondylitis. Conclusions Additional studies that take into account the shortcomings identified would be needed to produce definite conclusions. Few of the studied signs and symptoms seemed to be valuable diagnostics for radiculopathyh, ankylosing spondyliltis, and vertebral cancer. Reproducibility of signs and symptoms over time might be a valuable diagnostic criterion. However, this was neglected in almost all studies.
Forearm DXA Increases the Rate of Patients With Asymptomatic Primary Hyperparathyroidism Meeting Surgical Criteria.

INTRODUCTION A reduction in bone mineral density (BMD) is common in primary hyperparathyroidism (PHPT), above all at cortical sites. Guidelines for the management of asymptomatic PHPT (aPHPT) recommend a BMD evaluation at the lumbar spine, hip, and forearm. Surgery is recommended for patients with a T-score less than or equal to -2.5 at any of these sites. However, a BMD evaluation at the forearm is not routinely performed. AIM To evaluate the impact of measuring forearm BMD in the clinical management of aPHPT. SUBJECTS AND METHODS We retrospectively reviewed a prospective database of 172 patients with aPHPT, selecting the 116 patients in whom a dual x-ray absorptiometry (DXA) scan had been performed at all 3 sites. RESULTS Seventy-four out of 116 patients had a densitometric diagnosis of osteoporosis (OP) at any site, and the forearm was the only site involved in 13/74 (group A, 17.6% of osteoporotic patients and 11.2% of the whole aPHPT cohort). Patients belonging to group A were significantly older than the other aPHPT patients, whereas no difference was found in biochemical measurements. Six out of 13 patients belonging to group A (5.2% of the whole aPHPT cohort) fulfilled surgical criteria based only on a forearm T-score. CONCLUSIONS DXA at 3 sites revealed OP at the forearm, but not at the other sites, in 11.2% of aPHPT patients. Half of these cases met surgical criteria based on this one factor alone. These patients did not show any clinical (except age) or biochemical differences from the other patients. The implementation of forearm DXA increases the rate of patients with aPHPT meeting surgical criteria.
Carbon Balance of Sorghum Plants during Osmotic Adjustment to Water Stress.

The daily (24-hour) carbon balances of whole sorghum plants (Sorghum bicolor L. Moench cv BTX616) were continuously measured throughout 15 days of water stress, followed by rewatering and 4 more days of measurements. The plants were grown under controlled environment conditions typical of warm, humid, sunny days. During the first 12 days, osmotic potentials decreased in parallel with decreased water potentials to maintain pressure potentials near 0.5 kilojoules per kilogram (5 bars). Immediately before rewatering on day 15, the water potential was -3.0 kilojoules per kilogram. Osmotic adjustment at this point was 1.0 kilojoules per kilogram, as measured by the decrease in the water potential at zero turgor from its initial value of -1.4 kilojoules per kilogram.Gross input of carbon was less but the fraction retained was greater because a smaller fraction was lost through respiration in stressed plants than in unstressed plants. This was attributed to a lower rate of biomass synthesis, and conversely a higher rate of storage of photosynthate, due to inhibition of leaf expansion. The reduction in the cost associated with biomass synthesis more than balanced any metabolic cost of osmotic adjustment. The net daily gain of carbon was always positive in the stressed plants.There was a large burst of respiration on rewatering, due to renewed synthesis of biomass from stored photosynthate. Over the next 3 days, osmotic adjustment was lost and the daily carbon balance returned to that typical of nonstressed plants. Thus, osmotic adjustment allowed the stressed plants to accumulate biomass carbon throughout the cycle, with little additional metabolic cost. Carbon stored during stress was immediately available for biomass synthesis on rewatering.