C-5 modifications in N-acetyl-neuraminic acid: scope and limitations

Glycoconjugates containing sialic acid are involved in a large variety of biological phenomena, including cell-cell adhesion, recognition by viruses and bacteria, and oncogenesis. Therefore, they are important synthetic targets for the design of drugs and vaccines. In the last decades, different methodologies that improve yield and stereoselectivity in sialylation reactions have been investigated. This review summarizes the latest developments in the synthesis of C-5 modified sialic acid glycosyl donors and glycosyl acceptors and their application in the synthesis of alpha-sialosides.     

Structure based virtual screening of ligands to identify cysteinyl leukotriene receptor 1 antagonist

Montelukast and Zafirlukast are known leukotriene receptor antagonists prescribed in asthma treatment. However, these fall short as mono therapy and are frequently used in combination with inhaled glucocorticosteroids with or without long acting beta 2 agonists. Therefore, it is of interest to apply ligand and structure based virtual screening strategies to identify compounds akin to lead compounds Montelukast and Zafirlukast. Hence, compounds with structures having 95% similarity to these compounds were retrieved from NCBI׳s PubChem database. Compounds similar to lead were grouped and docked at the antagonist binding site of cysteinyl leukotriene receptor 1. This exercise identified compounds UNII 70RV86E50Q (Pub Cid 71587778) and Sure CN 9587085 (Pub Cid 19793614) with higher predicted binding compared to Montelukast and Zafirlukast. It is shown that the compound Sure CN 9587085 showed appreciable ligand receptor interaction compared to UNII 70RV86E50Q. Thus, the compound Sure CN 9587085 is selected as a potent antagonist to cysteinyl leukotriene receptor 1 for further consideration in vitro and in vivo validation.     

Automated birdsong recognition in complex acoustic environments: a review

Conservationists are increasingly using autonomous acoustic recorders to determine the presence/absence and the abundance of bird species. Unlike humans, these recorders can be left in the field for extensive periods of time in any habitat. Although data acquisition is automated, manual processing of recordings is labour intensive, tedious, and prone to bias due to observer variations. Hence automated birdsong recognition is an efficient alternative. However, only few ecologists and conservationists utilise the existing birdsong recognisers to process unattended field recordings because the software calibration time is exceptionally high and requires considerable knowledge in signal processing and underlying systems, making the tools less user‐friendly. Even allowing for these difficulties, getting accurate results is exceedingly hard. In this review we examine the state‐of‐the‐art, summarising and discussing the methods currently available for each of the essential parts of a birdsong recogniser, and also available software. The key reasons behind poor automated recognition are that field recordings are very noisy, calls from birds that are a long way from the recorder can be faint or corrupted, and there are overlapping calls from many different birds. In addition, there can be large numbers of different species calling in one recording, and therefore the method has to scale to large numbers of species, or at least avoid misclassifying another species as one of particular interest. We found that these areas of importance, particularly the question of noise reduction, are amongst the least researched. In cases where accurate recognition of individual species is essential, such as in conservation work, we suggest that specialised (species‐specific) methods of passive acoustic monitoring are required. We also believe that it is important that comparable measures, and datasets, are used to enable methods to be compared.     

The impact of environmental factors in birdsong acquisition using automated recorders

The use of automatic acoustic recorders is becoming a principal method to survey birds in their natural habitats, as it is relatively noninvasive while still being informative. As with any other sound, birdsong degrades in amplitude, frequency, and temporal structure as it propagates to the recorder through the environment. Knowing how different birdsongs attenuate under different conditions is useful to, for example, develop protocols for deploying acoustic recorders and improve automated detection methods, an essential part of the research field that is becoming known as ecoacoustics. This article presents playback and recapture (record) experiments carried out under different environmental conditions using twenty bird calls from eleven New Zealand bird species in a native forest and an open area, answering five research questions: (1) How does birdsong attenuation differ between forest and open space? (2) What is the relationship between transmission height and birdsong attenuation? (3) How does frequency of birdsong impact the degradation of sound with distance? (4) Is birdsong attenuation different during the night compared to the day? and (5) what is the impact of wind on attenuation? Bird calls are complex sounds; therefore, we have chosen to use them rather than simple tones to ensure that this complexity is not missed in the analysis. The results demonstrate that birdsong transmission was significantly better in the forest than in the open site. During the night, the attenuation was at a minimum in both experimental sites. Transmission height affected the propagation of the songs of many species, particularly the flightless ones. The effect of wind was severe in the open site and attenuated lower frequencies. The reverberations due to reflective surfaces masked higher frequencies (8 kHz) in the forest even at moderate distances. The findings presented here can be applied to develop protocols for passive acoustic monitoring. Even though the attenuation can be generalized to frequency bands, the structure of the birdsong is also important. Selecting a reasonable sampling frequency avoids unnecessary data accumulation because higher frequencies attenuate more in the forest. Even at moderate distances, recorders capture significantly attenuated birdsong, and hence, automated analysis methods for field recordings need to be able to detect and recognize faint birdsong.     

Who Has Used Internal Company Documents for Biomedical and Public Health Research and Where Did They Find Them?

Objective

To describe the sources of internal company documents used in public health and healthcare research.

Methods

We searched PubMed and Embase for articles using internal company documents to address a research question about a health-related topic. Our primary interest was where authors obtained internal company documents for their research. We also extracted information on type of company, type of research question, type of internal documents, and funding source.

Results

Our searches identified 9,305 citations of which 357 were eligible. Scanning of reference lists and consultation with colleagues identified 4 additional articles, resulting in 361 included articles. Most articles examined internal tobacco company documents (325/361; 90%). Articles using documents from pharmaceutical companies (20/361; 6%) were the next most common. Tobacco articles used documents from repositories; pharmaceutical documents were from a range of sources. Most included articles relied upon internal company documents obtained through litigation (350/361; 97%). The research questions posed were primarily about company strategies to promote or position the company and its products (326/361; 90%). Most articles (346/361; 96%) used information from miscellaneous documents such as memos or letters, or from unspecified types of documents. When explicit information about study funding was provided (290/361 articles), the most common source was the US-based National Cancer Institute. We developed an alternative and more sensitive search targeted at identifying additional research articles using internal pharmaceutical company documents, but the search retrieved an impractical number of citations for review.

Conclusions

Internal company documents provide an excellent source of information on health topics (e.g., corporate behavior, study data) exemplified by articles based on tobacco industry documents. Pharmaceutical and other industry documents appear to have been less used for research, indicating a need for funding for this type of research and well-indexed and curated repositories to provide researchers with ready access to the documents.     

Genetic variants in the cytochrome P450 2D6 gene in the Sri Lankan population

INTRODUCTION:

Cytochrome P450 2D6 (CYP2D6) enzymes are involved in the metabolism of a large number of commonly prescribed drugs such as antidepressants and cardiovascular drugs. The CYP2D6 *3, *4 and *14 variants associated with the loss of enzyme function; CYP2D6 *10 and *17 variants with reduced enzyme function; and CYP2D6 *2 variant with no effect on enzyme function. Establishing the frequency of these variant alleles in Sri Lankan population would be useful for optimizing pharmacotherapy with CYP2D6-substrate drugs.

OBJECTIVE:

The objective of this study was to determine the prevalence of CYP2D6 *2, *3, *4, *10, *14 and *17 variants in the main ethnic groups in the Sri Lankan population.

MATERIALS AND METHODS:

A total of 90 deoxyribonucleic acid (DNA) samples (30 each from Sinhalese, Tamils and Moors) were selected from a DNA resource at the Human Genetic Unit, Faculty of Medicine, University of Colombo. This collection had been made for population genetic studies from a random population based volunteers. Genotyping was performed using published polymerase chain reaction/restriction fragment length polymorphism methods.

RESULTS:

The prevalence of the CYP2D6 variants in Sinhalese, Sri Lankan Tamils and Moors respectively were CYP2D6 *2: 37%, 41.6% and 37.9%; CYP2D6 *3: 60.3%, 45% and 30%; CYP2D6 *4: 21.6%, 6.6% and 8.3%; CYP2D6 *10: 40%, 35% and 44%. CYP2D6 *14 and *17 variants were not identified.

CONCLUSION:

CYP2D6*3, *4 and *10 variants, which are associated with reduced or loss of CYP2D6 enzyme function were found in our population in significant frequencies. CYP2D6*4, which is reported to be a Caucasian variant was also found in all three ethnic groups.     

Characterization of a novel weak interaction between MUC1 and Src-SH3 using nuclear magnetic resonance spectroscopy

Breast cancer causes death through cancer cell migration and subsequent metastasis to distant organs. In vitro, the MUC1 mucin can mediate breast cancer cell migration by binding to intercellular adhesion molecule-1 (ICAM-1). This migration is dependent on MUC1 cytoplasmic domain (MUC1-CD) activation of the non-receptor tyrosine kinase, Src, possibly through competitive displacement of an inhibitory Src intramolecular SH3 binding. Therefore, we characterized the binding site and affinity of the MUC1-CD for Src-SH3 using multidimensional nuclear magnetic resonance (NMR) spectroscopy to monitor the titration of the (15)N labeled Src-SH3 domain with synthetic native and mutant peptides of MUC1-CD. The results revealed that the dissociation constant (K(d)) for the interaction of the native MUC1-CD peptides and Src-SH3 domain was weak with a K(d) of 2-3 mM. Notably, the SH3 residues most perturbed upon peptide binding were located outside the usual hydrophobic binding cleft in a previously described alternate binding site on the Src-SH3, suggesting that MUC1-CD binds to a non-canonical site. The binding characteristics outlined here suggest that the interaction between Src-SH3 and MUC1-CD represents a novel weak electrostatic interaction of the type which is increasingly recognized as important in transient and dynamic protein complexes required for cell migration and signal transduction. As such, this study forms the foundation for the design of specific inhibitors of this interaction which may target breast cancer metastases with exquisite specificity.     

Temporally-Patterned Magnetic Fields Induce Complete Fragmentation in Planaria

A tandem sequence composed of weak temporally-patterned magnetic fields was discovered that produced 100% dissolution of planarian in their home environment. After five consecutive days of 6.5 hr exposure to a frequency-modulated magnetic field (0.1 to 2 µT), immediately followed by an additional 6.5 hr exposure on the fifth day, to another complex field (0.5 to 5 µT) with exponentially increasing spectral power 100% of planarian dissolved within 24 hr. Reversal of the sequence of the fields or presentation of only one pattern for the same duration did not produce this effect. Direct video evidence showed expansion (by visual estimation ∼twice normal volume) of the planarian following the first field pattern followed by size reduction (estimated ∼1/2 of normal volume) and death upon activation of the second pattern. The contortions displayed by the planarian during the last field exposure suggest effects on contractile proteins and alterations in the cell membrane’s permeability to water.     

Birdsong Denoising Using Wavelets

Automatic recording of birdsong is becoming the preferred way to monitor and quantify bird populations worldwide. Programmable recorders allow recordings to be obtained at all times of day and year for extended periods of time. Consequently, there is a critical need for robust automated birdsong recognition. One prominent obstacle to achieving this is low signal to noise ratio in unattended recordings. Field recordings are often very noisy: birdsong is only one component in a recording, which also includes noise from the environment (such as wind and rain), other animals (including insects), and human-related activities, as well as noise from the recorder itself. We describe a method of denoising using a combination of the wavelet packet decomposition and band-pass or low-pass filtering, and present experiments that demonstrate an order of magnitude improvement in noise reduction over natural noisy bird recordings.