Using Parahydrogen to Hyperpolarize Amines, Amides, Carboxylic Acids, Alcohols, Phosphates and Carbonates

Hyperpolarization turns weak NMR and MRI responses into strong signals so normally impractical measurements are possible. We use parahydrogen here to rapidly hyperpolarize appropriate 1H, 13C, 15N and 31P responses of analytes such as NH3 and important amines such as phenylethylamine, amides such as acetamide, urea and methacrylamide, alcohols spanning methanol through octanol and glucose, the sodium salts of carboxylic acids such as acetic acid and pyruvic acid, sodium phosphate, disodium adenosine 5’triphosphate and sodium hydrogen carbonate. The associated signal gains are used to demonstrate it is possible to collect informative single-shot NMR spectra of these analytes in seconds at the micromole level in a 9.4 T observation field. To achieve these wide ranging signal gains, we first employ the Signal Amplification By Reversible Exchange (SABRE) process to hyperpolarize an amine or ammonia and then employ their exchangeable NH protons to relay polarization into the analyte without changing its identity. We found the 1H signal gains reach as high as 650-fold per proton, while for 13C, the corresponding signal gains achieved in a 1H-13C refocused INEPT experiment exceed 570-fold and those in a direct detected 13C measurement 400-fold. Thirty one examples are described to demonstrate the applicability of this technique

Beyond isolated word recognition

In this commentary we concur with Frost’s view of the centrality of universal principles in models of word identification. However, we argue that other processes in sentence comprehension also fundamentally constrain the nature of written word identification. Furthermore, these processes appear to be universal. We, therefore, argue that universality in word identification should not be considered in isolation, but instead in the context of other linguistic processes that occur during normal reading

MiRPara: a SVM-based software tool for prediction of most probable microRNA coding regions in genome scale sequences

<p>Abstract</p> <p>Background</p> <p>MicroRNAs are a family of ~22 nt small RNAs that can regulate gene expression at the post-transcriptional level. Identification of these molecules and their targets can aid understanding of regulatory processes. Recently, HTS has become a common identification method but there are two major limitations associated with the technique. Firstly, the method has low efficiency, with typically less than 1 in 10,000 sequences representing miRNA reads and secondly the method preferentially targets highly expressed miRNAs. If sequences are available, computational methods can provide a screening step to investigate the value of an HTS study and aid interpretation of results. However, current methods can only predict miRNAs for short fragments and have usually been trained against small datasets which don't always reflect the diversity of these molecules.</p> <p>Results</p> <p>We have developed a software tool, miRPara, that predicts most probable mature miRNA coding regions from genome scale sequences in a species specific manner. We classified sequences from miRBase into animal, plant and overall categories and used a support vector machine to train three models based on an initial set of 77 parameters related to the physical properties of the pre-miRNA and its miRNAs. By applying parameter filtering we found a subset of ~25 parameters produced higher prediction ability compared to the full set. Our software achieves an accuracy of up to 80% against experimentally verified mature miRNAs, making it one of the most accurate methods available.</p> <p>Conclusions</p> <p>miRPara is an effective tool for locating miRNAs coding regions in genome sequences and can be used as a screening step prior to HTS experiments. It is available at <url>http://www.whiov.ac.cn/bioinformatics/mirpara</url></p

A Simple and Cost-efficient Technique to Generate Hyperpolarized Long-lived 15N-15N Nuclear Spin Order in a Diazine by Signal Amplification by Reversible Exchange

Signal Amplification by Reversible Exchange (SABRE) is an inexpensive and simple hyperpolarization technique and is capable of boosting Nuclear Magnetic Resonance (NMR) sensitivity by several orders of magnitude. It utilizes the reversible binding of para-hydrogen as hydride ligands and a substrate of interest to a metal catalyst to allow polarization transfer from para-hydrogen to the substrate nuclear spins. The nuclear spin lifetime of the created magnetization sets a strict upper limit on experimental timeframe. Short nuclear spin lifetimes are therefore a challenge for hyperpolarized metabolic imaging prospects. In this report we demonstrate how hyperpolarization and long nuclear spin lifetime can simultaneously be achieved in nitrogen-15 containing pyridazine and phthalazine derivatives by SABRE. These reflect two distinct classes of 15N2-coupled species with respect to their chemical symmetry and thus show different nuclear spin lifetime with the pyridazine derivative having a singlet state lifetime of ca. 2.5 minutes, produced with a signal enhancement of ca. 2,700. In contrast the phthalazine derivative yields a superior 15,000-fold enhancement at 11.7 T but has a much shorter singlet lifetime

Renal function, sodium and water homeostasis in patients with idiopathic extrahepatic portal vein thrombosis compared with normal healthy controls

Objectives. To determine whether portal hypertension in the absence of liver disease contributes to changes in renal function and renal sodium and water handling.Methods. Nine patients with extrahepatic portal vein thrombosis (PVT) with normal liver function and histology were compared with 9 matched healthy control subjects. All underwent standard measurements of glomerular filtration rate and effective renal blood flow using inulin and paraaminohippuric acid (PAH) clearances, respectively. Sodium excretion and renin and aldosterone levels were studied before, during and after an intravenous saline infusion,Results. At baseline there were no differences in inulin clearance, PAH clearance, fractional excretion of sodium and free water excretion. During and after the saline infusion both groups showed a significant increase in sodium excretion with a reduction in water excretion, while the PAH and inulin clearances remained unchanged. Although aldosterone and renin levels both fell after the infusion, aldosterone levels were significantly lower in the PVT group. There were no other significant differences between the PVT and control groups.Conclusion. Renal function and sodium and water handling were comparable in healthy controls and patients with PVT. It is unlikely that portal hypertension alone plays a significant role in the impaired ability to excrete sodium and water in patients with liver cirrhosi

Calling time: How to remove fossil fuel sponsorships from sports, arts & events

Sports, arts and major events are deeply embedded in the Australian way of life. Weekend matches, concerts and festivals bring us together - to cheer, to share pride and excitement, to feel connected to each other and to keep building our national story. When we barrack for our beloved teams, discover the work of a new local artist or laugh until our cheeks hurt at a comedy show, we are taking part in a ritual that has shaped social and cultural life in Australia for generations. Climate change – driven by burning coal, oil and gas – is putting all of this at risk. From flooded festivals, to concerts cancelled by bushfire threats and unsafe heat disrupting play at the tennis, footy and more, climate change is wreaking havoc on the activities and events we love..

Improved protection in guinea pigs after vaccination with a recombinant BCG expressing MPT64 on its surface

Abstract The lack of an efficient vaccine against tuberculosis is still one of the major problems threatening global human health. In previous work we showed that expression of the protective antigen MPT64 on the surface of Mycobacterium bovis BCG, the only approved vaccine against tuberculosis, strongly improved its immunogenicity and protective potential in mice. In this work we demonstrate that the same recombinant strain is able to induce better protection than wild type BCG also in guinea pigs preventing Mycobacterium tuberculosis dissemination and lung pathology, making this strain a strong candidate for further testing

Signal Amplification by Reversible Exchange (SABRE): : From Discovery to Diagnosis

Signal Amplification by Reversible Exchange (SABRE) turns typically weak magnetic resonance responses into strong signals making previously impractical measurements possible. This technique has gained significant popularity due to its speed and simplicity. This minireview tracks the development of SABRE from the initial hyperpolarization of pyridine in 2009, to the point where 50% 1H polarization levels have be achieved in a di-deuterio-nicotinate, a key step in the pathway to potential clinical use. Simple routes to highly efficient 15N hyperpolarization and the creation of hyperpolarized long-lived magnetic states are illustrated. It finishes by describing how the recently reported SABRE-RELAY approach offers a route for parahydrogen to hyperpolarize a much wider array of molecular scaffolds, such as amides, alcohols, carboxylic acids and phosphates, than was previously thought possible. We predict that collectively these developments ensure that SABRE will significantly impact on both chemical analysis and the diagnosis of disease in the future

Binocular coordination: reading stereoscopic sentences in depth

The present study employs a stereoscopic manipulation to present sentences in three dimensions to subjects as they read for comprehension. Subjects read sentences with (a) no depth cues, (b) a monocular depth cue that implied the sentence loomed out of the screen (i.e., increasing retinal size), (c) congruent monocular and binocular (retinal disparity) depth cues (i.e., both implied the sentence loomed out of the screen) and (d) incongruent monocular and binocular depth cues (i.e., the monocular cue implied the sentence loomed out of the screen and the binocular cue implied it receded behind the screen). Reading efficiency was mostly unaffected, suggesting that reading in three dimensions is similar to reading in two dimensions. Importantly, fixation disparity was driven by retinal disparity; fixations were significantly more crossed as readers progressed through the sentence in the congruent condition and significantly more uncrossed in the incongruent condition. We conclude that disparity depth cues are used on-line to drive binocular coordination during reading.<br/