Enrichment of Two Isomeric Heparin Oligosaccharides Exhibiting Different Affinities toward Monocyte Chemoattractant Protein-1

Chemokine-GAG interactions are crucial to facilitate chemokine immobilization, resulting in the formation of chemokine gradients that guide cell migration. Here we demonstrate chromatographic isolation and purification of two heparin hexasaccharide isomers that interact with the oligomeric chemokine Monocyte Chemoattractant Protein-1 (MCP-1)/CCL2 with different binding affinities. The sequences of these two hexasaccharides were deduced from unique MS/MS product ions and HPLC compositional analysis. Ion mobility mass spectrometry (IM-MS) showed that the two isolated oligosaccharides have different conformations and both displayed preferential binding for one of the two distinct conformations known for MCP-1 dimers. A significant shift in arrival time distribution of close to 70 Å2 was observed, indicating a more compact protein:hexasaccharide conformation. Clear differences in the MS spectra between bound and unbound protein allowed calculation of Kd values from the resulting data. The structural difference between the two hexasaccharides was defined as the differential location of a single sulfate at either C-6 of glucosamine or C-2 of uronic acid in the reducing disaccharide, resulting in a 200-fold difference in binding affinity for MCP-1. These data indicate sequence specificity for high affinity binding, supporting the view that sulfate position, and not simply the number of sulfates, is important for heparan sulfate protein binding

PediDraw: A web-based tool for drawing a pedigree in genetic counseling

<p>Abstract</p> <p>Background</p> <p>Drawing a pedigree is a prerequisite in genetic counseling. In medical records, a pedigree is useful to document the family history of the patient. Drawing a pedigree is also necessary in collecting genetic resources for medical research such as positional cloning. Currently, most pedigrees are drawn by hand or by drawing software. Due to the special requirements in a standardized pedigree, generating a pedigree by these methods is usually time-consuming and requires professionals. This limits the usage of a pedigree as demanded in remote diagnosis or online counseling from the counselees to send an electronic pedigree.</p> <p>Results</p> <p>We developed an online pedigree drawing tool, PediDraw, which enables users to generate pedigrees after inputting the family information step-by-step on web. It outputs a pedigree or table to present a family history to the counselors.</p> <p>Conclusion</p> <p>PediDraw is a user-friendly web-based drawing tool. It is accessible via Internet.</p

An assessment of pulse transit time for detecting heavy blood loss during surgical operation

Copyright @ Wang et al.; Licensee Bentham Open. This is an open access article licensed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted, non-commercial use, distribution and reproduction in any medium, provided the work is properly cited.The main contribution of this paper is the use of non-invasive measurements such as electrocardiogram (ECG) and photoplethysmographic (PPG) pulse oximetry waveforms to develop a new physiological signal analysis technique for detecting blood loss during surgical operation. Urological surgery cases were considered as the control group due to its generality, and cardiac surgery as experimental group since it involves blood loss and water supply. Results show that the control group has the tendency of a reduction of the pulse transient time (PTT), and this indicates an increment in the blood flow velocity changes from slow to fast. While for the experimental group, the PTT indicates high values during blood loss, and low values during water supply. Statistical analysis shows considerable differences (i.e., P <0.05) between both groups leading to the conclusion that PTT could be a good indicator for monitoring patients' blood loss during a surgical operation.The National Science Council (NSC) of Taiwan and the Centre for Dynamical Biomarkers and Translational Medicine, National Central University, Taiwan

Properties of plasmoids observed in Saturn’s dayside and nightside magnetodisc

Plasmoid is a key structure for transferring magnetic flux and plasma in planetary magnetospheres. At Earth, plasmoids are key media which transfer energy and mass in the "Dungey Cycle". For giant planets, plasmoids are primarily generated by the dynamic processes associated with “Vasyliunas Cycle”. It is generally believed that planetary magnetotails are favorable for producing plasmoids. Nevertheless, recent studies reveal that magnetic field lines could be sufficiently stretched to allow magnetic reconnection in Saturn’s dayside magnetodisc. In the study, we report direct observations of plasmoids in Saturn’s dayside magnetodisc for the first time. Moreover, we perform a statistical investigation on the global plasmoid electron density distribution. The results show an inverse correlation between the nightside plasmoid electron density and local time, and the maximum plasmoid electron density around prenoon local time on the dayside. These results are consistent with the magnetospheric circulation picture associated with the "Vasyliunas Cycle"

Dirac Equation with Spin Symmetry for the Modified P\"oschl-Teller Potential in DD-dimensions

We present solutions of the Dirac equation with spin symmetry for vector and scalar modified P\"oschl-Teller potential within framework of an approximation of the centrifugal term. The relativistic energy spectrum is obtained using the Nikiforov-Uvarov method and the two-component spinor wavefunctions are obtain are in terms of the Jacobi polynomials. It is found that there exist only positive-energy states for bound states under spin symmetry, and the energy levels increase with the dimension and the potential range parameter $\alpha$.Comment: 9 pages and 1tabl

Risk factors for exacerbations and pneumonia in patients with chronic obstructive pulmonary disease: a pooled analysis.

BACKGROUND: Patients with chronic obstructive pulmonary disease (COPD) are at risk of exacerbations and pneumonia; how the risk factors interact is unclear. METHODS: This post-hoc, pooled analysis included studies of COPD patients treated with inhaled corticosteroid (ICS)/long-acting β2 agonist (LABA) combinations and comparator arms of ICS, LABA, and/or placebo. Backward elimination via Cox's proportional hazards regression modelling evaluated which combination of risk factors best predicts time to first (a) pneumonia, and (b) moderate/severe COPD exacerbation. RESULTS: Five studies contributed: NCT01009463, NCT01017952, NCT00144911, NCT00115492, and NCT00268216. Low body mass index (BMI), exacerbation history, worsening lung function (Global Initiative for Chronic Obstructive Lung Disease [GOLD] stage), and ICS treatment were identified as factors increasing pneumonia risk. BMI was the only pneumonia risk factor influenced by ICS treatment, with ICS further increasing risk for those with BMI <25 kg/m2. The modelled probability of pneumonia varied between 3 and 12% during the first year. Higher exacerbation risk was associated with a history of exacerbations, poorer lung function (GOLD stage), female sex and absence of ICS treatment. The influence of the other exacerbation risk factors was not modified by ICS treatment. Modelled probabilities of an exacerbation varied between 31 and 82% during the first year. CONCLUSIONS: The probability of an exacerbation was considerably higher than for pneumonia. ICS reduced exacerbations but did not influence the effect of risks associated with prior exacerbation history, GOLD stage, or female sex. The only identified risk factor for ICS-induced pneumonia was BMI <25 kg/m2. Analyses of this type may help the development of COPD risk equations

The Quantized Hall Insulator: A New Insulator in Two-Dimensions

Quite generally, an insulator is theoretically defined by a vanishing conductivity tensor at the absolute zero of temperature. In classical insulators, such as band insulators, vanishing conductivities lead to diverging resistivities. In other insulators, in particular when a high magnetic field (B) is added, it is possible that while the magneto-resistance diverges, the Hall resistance remains finite, which is known as a Hall insulator. In this letter we demonstrate experimentally the existence of another, more exotic, insulator. This insulator, which terminates the quantum Hall effect series in a two-dimensional electron system, is characterized by a Hall resistance which is approximately quantized in the quantum unit of resistance h/e^2. This insulator is termed a quantized Hall insulator. In addition we show that for the same sample, the insulating state preceding the QHE series, at low-B, is of the HI kind.Comment: 4 page

Can intravenous oxytocin infusion counteract hyperinflammation in COVID-19 infected patients?

Objectives Based on its well-documented anti-inflammatory and restorative properties we propose trials with the natural hormone oxytocin for treatment of hospitalised Covid-19 patients. Methods We searched for, retrieved, and commented on specific literature regarding multiple functions of oxytocin with a special focus on its modulation of inflammatory, immune, and restorative functions. Results Available data gathered in animals and humans support the anti-inflammatory properties of oxytocin. The multiple anti-inflammatory effects of oxytocin have been demonstrated in vitro and in vivo in various animal models and also in humans in response to intravenous infusion of oxytocin. Furthermore, oxytocin has been documented to activate several types of protective and restorative mechanisms and to exert positive effects on the immune system. Conclusions In addition, to being anti-inflammatory, it may be hypothesised, that oxytocin may be less suppressive on adaptive immune systems, as compared with glucocorticoids. Finally, by its restorative effects coupled with its anti-stress and healing properties, oxytocin may shorten the recovery period of the Covid-19 patients

Empirical study of correlated survival times for recurrent events with proportional hazards margins and the effect of correlation and censoring.

Background: In longitudinal studies where subjects experience recurrent incidents over a period of time, such as respiratory infections, fever or diarrhea, statistical methods are required to take into account the within-subject correlation. Methods: For repeated events data with censored failure, the independent increment (AG), marginal (WLW) and conditional (PWP) models are three multiple failure models that generalize Cox"s proportional hazard model. In this paper, we revise the efficiency, accuracy and robustness of all three models under simulated scenarios with varying degrees of within-subject correlation, censoring levels, maximum number of possible recurrences and sample size. We also study the methods performance on a real dataset from a cohort study with bronchial obstruction. Results: We find substantial differences between methods and there is not an optimal method. AG and PWP seem to be preferable to WLW for low correlation levels but the situation reverts for high correlations. Conclusions: All methods are stable in front of censoring, worsen with increasing recurrence levels and share a bias problem which, among other consequences, makes asymptotic normal confidence intervals not fully reliable, although they are well developed theoretically

Gene expression profiling and silencing reveal that monolignol biosynthesis plays a critical role in penetration defence in wheat against powdery mildew invasion

Cell wall apposition (CWA) formation is one of the first lines of defence used by plants to halt invading fungi such as powdery mildew. Lignin is a complex polymer of hydroxylated and methoxylated phenylpropane units (monolignols) and lignification renders the cell wall more resistant to pathogen attack. The role of monolignol biosynthesis in CWA-mediated defence against powdery mildew penetration into cereals is demonstrated here using RNA interference (RNAi)-mediated gene silencing and enzyme-specific inhibitors. Thirteen cDNAs representing eight genes involved in monolignol biosynthesis were cloned from an expression sequence tag (EST) library derived from the epidermis of diploid wheat (Triticum monococcum) infected with Blumeria graminis f. sp. tritici (Bgt). Differential expression patterns were found for these genes in susceptible and resistant plants after infection. Transcripts of phenylalanine ammonia lyase (PAL), caffeic acid O-methyltransferase (CAOMT), ferulic acid hydroxylase (FAH), caffeoyl-CoA O-methyltransferase (CCoAMT), and cinnamyl alcohol dehydrogenase (CAD) were accumulated, particularly in the epidermis. RNAi-mediated transient gene silencing in the epidermis led to a higher penetration efficiency of Bgt than in the controls. Gene silencing also compromised penetration resistance to varying degrees with different genes against an inappropriate pathogen, B. graminis f. sp. hordei (Bgh). Co-silencing led to greater penetration of Bgt or Bgh than when the genes were silenced separately. Fluorescence emission spectra analyses revealed that gene silencing hampered host autofluorescence response at fungal contact sites. These results illustrate that monolignol biosynthesis is critically important for host defence against both appropriate and inappropriate pathogen invasion in wheat