Miracle-dz/UniFAR-FTUs huggingface dataset:
Regulated interactions of the norepineprhine transporter by the actin and microtubule cytoskeletons

One role of the actin cytoskeleton is to maintain the structural morphology and activity of the pre‐synaptic terminal. We sought to determine if the actin cytoskeleton plays a role in regulating interactions between the norepinephrine transporter (NET) and alpha‐Synuclein (α‐Syn), two proteins expressed in the pre‐synaptic terminal. In cells transfected with either 0.5 μg/mL or 3 μg/mL of α‐Syn and 1 μg/mL of NET DNA, treatment with cytochalasin D, an actin depolymerizing agent, caused a dose‐dependent decrease and increase, respectively, in [3H]‐NE uptake. Protein interactions between NET, β‐actin, and α‐Syn were modified, along with levels of surface transporters. Treatment of primary brainstem neurons and frontal cortex synaptosomes with cytochalasin D caused a 115% and 28% increase, respectively, in NET activity. Depolymerization of both actin and microtubules did not alter NET activity in cells with 0.5 μg/mL α‐Syn, but caused an increase in [3H]‐NE uptake in cells transfected with 3 μg/mL of α‐Syn and primary neurons. This is the first direct demonstration of NET activity being regulated via actin and modulated by interactions with α‐Syn.
Clinico-pathological Evaluation of Ciliary Dyskinesia: Diagnostic Role of Electron Microscopy

From November 1995 to May 2002, the authors studied 59 children with suspected primary ciliary dyskinesia (PCD). Samples of ciliated respiratory epithelium were obtained by nasal brushing from 44 patients and by biopsy of bronchial mucosa from 15 patients. Thirty-four/Fifty-nine samples were suitable to obtain a quali-quantitative evaluation of ultrastructural ciliary abnormalities. Many ciliary and axoneme alterations were described. This study revealed that quantitative and qualitative ultrastructural assessment of respiratory epithelial cilia plays an important role in the differentiation between primary, secondary, and borderline ciliary abnormalities. Early diagnosis of PCD with appropriate clinical follow-up and treatment is important to prevent irreversible lung tissue damage, namely bronchiectasis.
Changes in the Level of Immunoglobulins and CD4/CD8 Ratio in Young and Aged Mice with Estradiol Deficiency

ABSTRACT Studies demonstrated that deficiency in 17β-estradiol (E2) in postmenopausal women influences their immune system. However, few studies have reported alterations in immunologic presentation during nonnatural menopause in young females. Here we compared the differences in immune response between young C57BL/6N mice with surgical or medical variectomy and aged C57BL/6N mice with the common feature of E2 deficiency following Con A stimulation. We observed inverted CD4/CD8 ratios in the aged group and apparent reduced production of serum immunoglobin (Ig)G, IgA, and IgM in the surgical group, whereas changes in immune parameters in the medical group were moderate. These data suggested that the immunological response to Con A stimulus differed among the three groups and that E2 deficiency was only partially responsible for the development of immune deficiency in aged mice.
Connexin43 PDZ2 Binding Domain Mutants Create Functional Gap Junctions and Exhibit Altered Phosphorylation

Connexin43 (Cx43) is the most abundantly expressed gap junction protein. The C-terminal tail of Cx43 is important for regulation of gap junctions via phosphorylation of specific tyrosine and serine residues and through interactions with cellular proteins. The C-terminus of Cx43 has been shown to interact with the PDZ2 domain of the tight and adherens junction associated zona occludens 1 (ZO-1) protein. Analysis of the PDZ2 binding domain of Cx43 indicated that positions −3 and −2, and the final hydrophobic amino acid at the C-terminus, are critical for ZO-1 binding. In addition, the C-termini of connexins 40 and 45, but not Cx32, interacted with ZO-1. To evaluate the functional significance of the Cx43-ZO-1 interaction, Cx43 wild type (Cx43wt) and mutants lacking either the C-terminal hydrophobic isoleucine (Cx43ΔI382) or the last five amino acids (Cx43Δ378–382), required for ZO-1 binding in vitro, were introduced into a Cx43-deficient MDCK cell line. In vitro binding studies and coimmunoprecipitation assays indicated that these Cx43 mutants failed to interact with ZO-1. Confocal and deconvolution microscopy revealed that a fraction of Cx43wt colocalized with ZO-1 at the plasma membrane. A similar colocalization pattern was observed for the Cx43ΔI382 and Cx43Δ378–382 mutants, which were translocated to the plasma membrane and formed functional gap junction channels. The wt and mutant Cx43 appeared to have similar turnover rates. However, the P2 and P3 phosphoisoforms of the Cx43 mutants were significantly reduced compared to Cx43wt. These studies indicated that the interaction of Cx43 with ZO-1 may contribute to the regulation of Cx43 phosphorylation.
Chm7 and Heh1 collaborate to link nuclear pore complex quality control with nuclear envelope sealing

The integrity of the nuclear envelope barrier relies on membrane remodeling by the ESCRTs, which seal nuclear envelope holes and contribute to the quality control of nuclear pore complexes (NPCs); whether these processes are mechanistically related remains poorly defined. Here, we show that the ESCRT‐II/III chimera, Chm7, is recruited to a nuclear envelope subdomain that expands upon inhibition of NPC assembly and is required for the formation of the storage of improperly assembled NPCs (SINC) compartment. Recruitment to sites of NPC assembly is mediated by its ESCRT‐II domain and the LAP2‐emerin‐MAN1 (LEM) family of integral inner nuclear membrane proteins, Heh1 and Heh2. We establish direct binding between Heh2 and the “open” forms of both Chm7 and the ESCRT‐III, Snf7, and between Chm7 and Snf7. Interestingly, Chm7 is required for the viability of yeast strains where double membrane seals have been observed over defective NPCs; deletion of CHM7 in these strains leads to a loss of nuclear compartmentalization suggesting that the sealing of defective NPCs and nuclear envelope ruptures could proceed through similar mechanisms.
The transverse field Richtmyer-Meshkov instability in magnetohydrodynamics

The magnetohydrodynamic Richtmyer-Meshkov instability is investigated for the case where the initial magnetic field is unperturbed and aligned with the mean interface location. For this initial condition, the magnetic field lines penetrate the perturbed density interface, forbidding a tangential velocity jump and therefore the presence of a vortex sheet. Through simulation, we find that the vorticity distribution present on the interface immediately after the shock acceleration breaks up into waves traveling parallel and anti-parallel to the magnetic field, which transport the vorticity. The interference of these waves as they propagate causes the perturbation amplitude of the interface to oscillate in time. This interface behavior is accurately predicted over a broad range of parameters by an incompressible linearized model derived presently by solving the corresponding impulse driven, linearized initial value problem. Our use of an equilibrium initial condition results in interface motion produced solely by the impulsive acceleration. Nonlinear compressible simulations are used to investigate the behavior of the transverse field magnetohydrodynamic Richtmyer-Meshkov instability, and the performance of the incompressible model, over a range of shock strengths, magnetic field strengths, perturbation amplitudes and Atwood numbers.
Iron Metabolism and Requirements in Early Childhood: Do We Know Enough?: A Commentary by the ESPGHAN Committee on Nutrition

*University of Lancashire, Lancashire, United Kingdom; †University of Milano, Milano, Italy; ‡University of Lund, Malmo, Sweden; §Hopital des Enfants Malades, Paris, France; Hopital Necker Enfants-Malades, Paris, France, ¶Umea University, Umea, Sweden; #University of Munich, Munich, Germany; **Free University of Amsterdam, Amsterdam, The Netherlands; ††Royal Veterinary and Agricultural University, Frederiksberg, Denmark; ‡‡CHUV University Hospital, Lausanne, Switzerland; §§University of Liege, Liege, Belgium; Medical University of Warsaw, Warsaw, Poland; and ¶¶University of Glasgow, Glasgow, United Kingdom
Effects of salicylic acid on post-ischaemic ventricular function and purine efflux in isolated mouse hearts

Abstract Acetyl salicylic acid (aspirin) is one of the most widely used drugs in the world. Various plasma concentrations of aspirin and its predominant metabolite, salicylic acid, are required for its antiarthritic (1.5–2.5 mM), anti-inflammatory (0.5–5.0 mM) or antiplatelet (0.18–0.36 mM) actions. A recent study demonstrated the inhibitory effects of both aspirin and salicylic acid on oxidative phosphorylation and ATP synthesis in isolated rat cardiac mitochondria in a dose-dependent manner (0–10 mM concentration range). In this context, the present study was conducted to determine the effects of salicylic acid on inosine efflux (a potential biomarker of acute cardiac ischaemia) as well as cardiac contractile function in the isolated mouse heart following 20 min of zero-flow global ischaemia. Inosine efflux was found at significantly higher concentrations in ischaemic hearts perfused with Krebs buffer fortified with 1.0 mM salicylic acid compared with those without salicylic acid (12575±3319 vs. 1437±348 ng ml−1 min−1, mean±SEM, n=6 per group, p<0.01). These results indicate that 1.0 mM salicylic acid potentiates 8.8-fold ATP nucleotide purine catabolism into its metabolites (e.g. inosine, hypoxanthine). Salicylic acid (0.1 or 1.0 mM) did not appreciably inhibit purine nucleoside phosphorylase (the enzyme converts inosine to hypoxanthine) suggesting the augmented inosine efflux was due to the salicylic acid effect on upstream elements of cellular respiration. Whereas post-ischaemic cardiac function was further depressed by 1.0 mM salicylic acid, perfusion with 0.1 mM salicylic acid led to a remarkable functional improvement despite moderately increased inosine efflux (2.7-fold). We conclude that inosine is a sensitive biomarker for detecting cardiac ischaemia and salicylic acid-induced effects on cellular respiration. However, the inosine efflux level appears to be a poor predictor of the individual post-ischaemic cardiac functional recovery in this ex vivo model.
Conformational analysis and NMR assignments of dibenzoxocins from Sappan Lignum

Dibenzoxocin derivatives are characteristic chemical constituents from Sappan Lignum, the dried heartwood of Caesalpinia sappan L. (Leguminosae), a traditional Chinese medicine. As major active constituents in Sappan Lignum, they have antioxidant and anti-inflammatory activities. In the structural skeleton of dibenzoxocin derivatives, there are two benzene rings and one octatomic ether ring. Less than ten compounds with this type of skeleton have been reported (Fig. 1). Compound 1, named as protosappanin B, was first reported in 1986; the structure was established as 3, 7, 10, 11-tetrahydroxy-7, 8-dihydro-7(6H)dibenz [b, d] oxocinemethanol. At the same time, S configuration was assigned to its biphenyl system by circular dichroism (CD) spectrum, and S configuration was tentatively assigned to C-7 of 1. But the NMR data were not assigned completely. While in 2008, 1 was reported as a mixture of protosappanin B and isoprotosappanin B again. In our study, we noticed that many dibenzoxocin derivatives, including 1, exhibit two sets of signals in H and C NMR spectra. To explain the phenomena, two different points of views have been proposed. Some think there are two interconvertible conformers in solution, but others explained phenomena as a mixture of two compounds. None of them had a strong NMR evidence to support their view because of the low resolution in NMR. We are in favor of the former one, and this paper is to verify this viewpoint. There are few literatures about the conformation of dibenzoxocins, but the structure of dibenzoxocin derivatives is similar to the 5, 6, 7, 8-tetrahydrodibenzo [a, c] cyclooctene (2), except for one oxygen atom in the ring. According to the literatures, 2 exist in two interconvertible conformers, a twist boat-chair (TBC) form and a twist boat (TB) (Fig. 2). At the same time, the two benzene rings may exist in two possible rotamers because of the hindered biaryl rotation. Similar to the dibenzocyclooctadiene type lignans, such as schizandrin, the axis of chirality is defined as aS or aR (shown in Figs. 1 and 2). [16] These forms interconvert via the process as follows:(1) TBC-S→ TB-S, (2) TB-S→ TB-R and (3) TB-R→ TBC-R. For the conformational analysis of dibenzoxocin derivatives, it can be divided into two problems which biphenyl rotamer, aS or aR is preferred and which form, TBC or TB, is predominant for a particular biphenyl rotamer. Herein, the conformation of dibenzoxocin derivatives is discussed based on NMR data and CD results. The present paper deals with the stereochemistry of dibenzoxocin derivatives by the NMR and CD experiments of variable temperature. The ideal 1D and 2D NMR spectra were obtained at low temperature, and the complete NMR assignments were successfully achieved. And the conformation was elucidated unambiguously.
Risk, Vulnerability, and Protective Processes of Parental Expressed Emotion for Children's Peer Relationships in Contexts of Parental Violence

This study examined risk, vulnerability, and protective processes of parental expressed emotion for children's peer relationships in families living in emergency shelters with high rates of exposure to parental violence (EPV). Parental criticism and negativity were hypothesized to exacerbate the association between EPV and poorer peer relations, whereas parental warmth was expected to buffer this association. Participants included 138 homeless parents (M = 30.77 years, SD = 6.33, range = 20.51–57.32 years; 64% African American, 12% Caucasian, 24% other) and their 4-to 6-year-old children (43.5% male; M = 4.83, SD = .58, range = 4.83–6.92 years; 67% African American, 2% Caucasian, 31% other). Families were assessed during the summer at three urban shelters, with parents completing the Five-Minute Speech Sample (FMSS), later scored for criticism, negativity, and warmth, and interview items about EPV. Teachers were subsequently contacted in the fall about children's classroom behavior, and they provided ratings of peer relations. Demographic factors, parental internalizing symptoms, and observed parental harshness were examined as covariates. Regression analyses indicated an interaction of EPV and warmth, consistent with a moderating effect of expressed emotion for EPV and peer relations, although no interactions were found for criticism or negativity. Observed harshness also directly predicted worse peer relations. Parental warmth may be protective for positive peer relations among impoverished families with high levels of EPV. The FMSS is discussed as an efficient tool with potential for both basic clinical research and preventative interventions designed to target or assess change in parental expressed emotion.
PREDICTIVE VALUE OF MONOCYTE HISTOCOMPATIBILITY LEUKOCYTE ANTIGEN‐DR EXPRESSION AND PLASMA INTERLEUKIN‐4 AND ‐10 LEVELS IN CRITICALLY ILL PATIENTS WITH SEPSIS

&NA; It has been suggested that excessive activation of the anti‐inflammatory pathways in sepsis may lead to poor outcome of patients with sepsis. The aim of this study was to test the value of histocompatibility leukocyte antigen (HLA)‐DR‐expression on blood monocytes and plasma levels of interleukin (IL)‐4 and ‐10 in prediction of hospital mortality in patients with sepsis. Sixty‐one critically ill patients with sepsis were prospectively enrolled to this study in two university hospital intensive care units. Survivors (n = 41) and nonsurvivors (n = 20) differed significantly in HLA‐DR expression at admission: survivors' median 84% (interquartile range 64%‐98%) versus nonsurvivors' median 62% (interquartile range 47%‐83%, P = 0.025 by Mann‐Whitney test). Similarly, the analysis revealed statistically significant differences between survivors and nonsurvivors in admission plasma IL‐10 levels and in admission Sequential Organ Failure Assessment (SOFA) and Acute Physiology and Chronic Health Evaluation (APACHE) II scores, but not in IL‐4 levels. The areas under receiver operating curves (AUC) showed that both monocyte HLA‐DR expression and plasma IL‐4 level showed poor discriminative power in prediction of hospital mortality (AUC < 0.70). Only IL‐10 levels on days 1 and 2 showed reasonable predictive power (AUCs 0.706 and 0.725, respectively). The highest AUC values were those of APACHE‐II (0.786) and admission SOFA score (0.763). In conclusion, APACHE II and SOFA scores on admission showed better discriminatory power than HLA‐DR expression and IL‐10 and IL‐4 levels in prediction of hospital mortality in critically ill patients with sepsis.
Wavelet Transform Based Protein Decoy Discrimination

A decoy discrimination method using wavelet analysis is presented in this paper. Through discrete wavelet decomposition and reconstruction, low frequencies of physicochemical properties from amino acid sequences and solvent accessibility area of residues from the protein three dimensioanl conformations are extracted and compared to find the profile similarity between the protein sequence and its three dimensional conformation. With the assumption that the protein native state conformation should have more profile similarity to its sequence than any other decoys, a scoring function evaluating the similarity is developed. This method was trained and tested by the first_decoys set in rosetta decoy set. The test results show that 73% protein native structure has the top 5 largest score. Considering the simplicity of our method, wavelet analysis is a promising way to deal with the decoy discrimination problem. Keywords-decoy discrimination; protein structure; wavelet analysis.
Agricultural expansion, forest products as safety nets, and deforestation

This paper aims to address the impact on deforestation of the use of forest products as safety nets by poor agricultural households. Two safety-net uses may be implemented: the diversification strategy and the coping strategy. With both strategies, crop risk reduction, lower risk aversion and larger population increase tropical deforestation. Forest profitability always tends to increase the forest cover in the diversification case. Conversely, considering the coping strategy, two opposite effects determine the impact of forest profitability on the forest cover: a portfolio effect and an insurance effect. Finally, the household is better off and deforests less when using the diversification strategy instead of the coping strategy.
Study of detection times for liver stiffness evaluation by shear wave elastography.

AIM To investigate enough valid measurements (VMs) to assess liver fibrosis in chronic hepatitis B patients (CHB). METHODS One hundred and twelve CHB patients (25 women, 87 men) with a mean age of 38.43 years received liver stiffness evaluations using real-time shear wave elastography for 10 VMs. All patients underwent liver biopsy. Based on the biopsy pathology, the liver stiffness data obtained from different VMs (1, 2, 3, 5 and 10 times) were compared for the evaluation of liver fibrosis. The correlation between the elastic modulus means of the liver obtained from different VMs of detection at each pathological stage was analysed. The receiver operating characteristic (ROC) curve was employed to determine the diagnostic performance of different VMs of detection, and the areas under the ROC curve of different groups were compared. RESULTS The liver stiffness values obtained from 1 VM, 2 VMs, 3 VMs, 5 VMs and all 10 VMs for stage F0 were 6.95 ± 2.01 kPa, 6.87 ± 1.83 kPa, 6.90 ± 1.88 kPa, 6.95 ± 1.93 kPa and 7.15 ± 1.89 kPa, respectively (F = 0.043, P = 0.996). For stage F1, these values were 7.12 ± 1.72 kPa, 7.24 ± 1.72 kPa, 7.21 ± 1.74 kPa, 7.10 ± 1.78 kPa and 7.04 ± 1.70 kPa, respectively (F = 0.075, P = 0.990). For stage F2, they were 9.37 ± 3.87 kPa, 9.18 ± 3.68 kPa, 9.19 ± 3.81 kPa, 9.18 ± 3.81 kPa and 9.19 ± 3.53 kPa, respectively (F = 0.012, P = 1.000). For stage F3, these were 11.91 ± 3.88 kPa, 11.78 ± 4.04 kPa, 11.83 ± 4.07 kPa, 11.94 ± 4.17 kPa and 12.00 ± 4.02 kPa, respectively (F = 0.010, P = 1.000). For stage F4, the readings were 19.30 ± 7.63 kPa, 19.40 ± 7.36 kPa, 19.54 ± 7.43 kPa, 19.73 ± 7.21 kPa and 20.25 ± 7.22 kPa, respectively (F = 0.054, P = 0.995). There were no significant differences between these groups. Intraclass correlation coefficients among different pathological stages (F0-F4) with different detection VMs were 0.995, 0.993, 0.996, 0.994 and 0.996, respectively. The mean elasticity values from 1 VM, 2 VMs, 3 VMs, 5 VMs and 10 VMs can accurately distinguish fibrosis stages (F0 vs F1234, F01 vs F234, F012 vs F34 and F0123 vs F4) with no significant differences in the five groups (P > 0.05 for all). CONCLUSION One VM may be sufficient to assess liver fibrosis by using SWE without any significant loss of accuracy in patients with CHB. However, future studies of larger patient samples are necessary for the validation of this method.
Risk Factors for Hospital Readmission in Patients with Chronic Obstructive Pulmonary Disease

Background: Hospital readmissions for acute exacerbation of chronic obstructive pulmonary disease (COPD) are one of the leading causes of healthcare expenditures worldwide. Objectives: To identify risk factors for hospital readmission in COPD patients. Methods:We prospectively evaluated 129 consecutive patients hospitalized for acute exacerbation of COPD. Clinical, spirometric and arterial blood gas variables were measured during hospitalization. Socioeconomic characteristics, comorbidity, dyspnea, functional dependence, depression, social support and quality of life were also analyzed. Readmission was defined as one or more hospitalizations in the following year. Results:During the follow-up period, 75 (58.5%) patients were readmitted. In bivariate analysis, readmission was associated with previous hospitalization for COPD in the past year, dyspnea scale, PaCO2 at discharge, depression, cor pulmonale, chronic domiciliary oxygen and quality of life measured by the St. George’s Respiratory Questionnaire. In multivariate analysis, the best predictor of readmission was the combination of hospitalization for COPD in the previous year (odds ratio, OR: 4.27; 95% confidence interval, CI: 1.5–12), the total score of the St. George’s Respiratory Questionnaire ≧50 points (OR: 2.36; 95% CI: 1.03–5.04) and PaCO2 at discharge ≧45 mm Hg (OR: 2.18; 95% CI: 0.84–5.06). With this model, the probability of readmission for patients without any of these variables was 7%, while it was 70% for the patients with all three variables present. Conclusion: The combination of quality of life, hospitalization for COPD in the previous year and hypercapnia at discharge are useful predictors of readmission at 1 year.
Blood Transfusion in Nocturnal Haemoglobinuria

The very short incubation period would, however, make this improbable unless the infection had been an ante-natal one. 4. The fact that infants seldom or never seem to have a recurrence of the infection after removal to the " septic " nursery has been referred to. On one occasion this did occur, and four infants cured and ready to go out showed a fresh infection simultaneously, two with conjunctivitis and two with a rash on the face. A nurse known to be a carrier of Staph. aureus and to suffer occasionally from folliculitis of the nares had been transferred three days previously to this ward. A comparison of her cultures with those of the strains isolated from the infants' lesions showed three of them to be closely similar, and it seems probable that the new infection was derived from her. The table below shows the similarity of the cultures of Nurse A to those from the two cases of conjunctivitis and one pustule.