'Your DNA, Your Say': global survey gathering attitudes toward genomics: design, delivery and methods.

Our international study, 'Your DNA, Your Say', uses film and an online cross-sectional survey to gather public attitudes toward the donation, access and sharing of DNA information. We describe the methodological approach used to create an engaging and bespoke survey, suitable for translation into many different languages. We address some of the particular challenges in designing a survey on the subject of genomics.

The Structural Basis of Calcium-Dependent Inactivation of the Transient Receptor Potential Vanilloid 5 Channel.

The transient receptor potential vanilloid channel subfamily member 5 (TRPV5) is a highly selective calcium ion channel predominately expressed in the kidney epithelium that plays an essential role in calcium reabsorption from renal infiltrate. In order to maintain Ca homeostasis, TRPV5 possesses a tightly regulated negative feedback mechanism, where the ubiquitous Ca binding protein calmodulin (CaM) directly binds to the intracellular TRPV5 C-terminus, thus regulating TRPV5. Here we report on the characterization of the TRPV5 C-terminal CaM binding site and its interaction with CaM at an atomistic level.

A FAIR guide for data providers to maximise sharing of human genomic data.

It is generally acknowledged that, for reproducibility and progress of human genomic research, data sharing is critical. For every sharing transaction, a successful data exchange is produced between a data consumer and a data provider. Providers of human genomic data (e.

DNAdigest and Repositive: Connecting the World of Genomic Data.

There is no unified place where genomics researchers can search through all available raw genomic data in a way similar to OMIM for genes or Uniprot for proteins. With the recent increase in the amount of genomic data that is being produced and the ever-growing promises of precision medicine, this is becoming more and more of a problem. DNAdigest is a charity working to promote efficient sharing of human genomic data to improve the outcome of genomic research and diagnostics for the benefit of patients.

The need to redefine genomic data sharing: A focus on data accessibility.

DNAdigest's mission is to investigate and address the issues hindering efficient and ethical genomic data sharing in the human genomics research community. We conducted contextual interviews with human genomics researchers in clinical, academic or industrial R&D settings about their experience with accessing and sharing human genomic data. The qualitative interviews were followed by an online survey which provided quantitative support for our findings.

Structural analysis of calmodulin binding to ion channels demonstrates the role of its plasticity in regulation.

The Ca²⁺-binding protein calmodulin (CaM) is a well-known regulator of ion-channel activity. Consequently, the Protein Data Bank contains many structures of CaM in complex with different fragments of ion channels that together display a variety of binding modes. In addition to the canonical interaction, in which CaM engages its target with both its domains, many of the ion-channel-CaM complexes demonstrate alternative non-canonical binding modes that depend on the target and experimental conditions.

Urinary plasmin inhibits TRPV5 in nephrotic-range proteinuria.

Urinary proteins that leak through the abnormal glomerulus in nephrotic syndrome may affect tubular transport by interacting with membrane transporters on the luminal side of tubular epithelial cells. Patients with nephrotic syndrome can develop nephrocalcinosis, which animal models suggest may develop from impaired transcellular Ca(2+) reabsorption via TRPV5 in the distal convoluted tubule (DCT). In nephrotic-range proteinuria, filtered plasminogen reaches the luminal side of DCT, where it is cleaved into active plasmin by urokinase.

The TRPV5/6 calcium channels contain multiple calmodulin binding sites with differential binding properties.

The epithelial Ca(2+) channels TRPV5/6 (transient receptor potential vanilloid 5/6) are thoroughly regulated in order to fine-tune the amount of Ca(2+) reabsorption. Calmodulin has been shown to be involved into calcium-dependent inactivation of TRPV5/6 channels by binding directly to the distal C-terminal fragment of the channels (de Groot et al. in Mol Cell Biol 31:2845-2853, 12).

Expression and purification of the C-terminal fragments of TRPV5/6 channels.

The transient receptor potential vanniloid 5 and 6 (TRPV5 and TRPV6) Ca(2+)-ion channels are crucial for the regulation of minute-to-minute whole body calcium homeostasis. They act as the gatekeepers of active Ca(2+) reabsorption in kidney and intestine, respectively. In spite of the great progress in the TRP channels characterization, very little is known at the atomic level about their structure and interactions with other proteins.

Molecular mechanisms of calmodulin action on TRPV5 and modulation by parathyroid hormone.

The epithelial Ca(2+) channel transient receptor potential vanilloid 5 (TRPV5) constitutes the apical entry gate for active Ca(2+) reabsorption in the kidney. Ca(2+) influx through TRPV5 induces rapid channel inactivation, preventing excessive Ca(2+) influx. This inactivation is mediated by the last ∼30 residues of the carboxy (C) terminus of the channel.

Overview on the use of NMR to examine protein structure.

Any protein structure determination process contains several steps, starting from obtaining a suitable sample, then moving on to acquiring data and spectral assignment, and lastly to the final steps of structure determination and validation. This unit describes all of these steps, starting with the basic physical principles behind NMR and some of the most commonly measured and observed phenomena such as chemical shift, scalar and residual coupling, and the nuclear Overhauser effect. Then, in somewhat more detail, the process of spectral assignment and structure elucidation is explained.

NMR structures of apo L. casei dihydrofolate reductase and its complexes with trimethoprim and NADPH: contributions to positive cooperative binding from ligand-induced refolding, conformational changes, and interligand hydrophobic interactions.

In order to examine the origins of the large positive cooperativity (ΔG(0)(coop) = -2.9 kcal mol(-1)) of trimethoprim (TMP) binding to a bacterial dihydrofolate reductase (DHFR) in the presence of NADPH, we have determined and compared NMR solution structures of L. casei apo DHFR and its binary and ternary complexes with TMP and NADPH and made complementary thermodynamic measurements.

Isolation and characterization of site-specific DNA-methyltransferases from Bacillus coagulans K.

Two site-specific DNA methyltransferases, M.BcoKIA and M.BcoKIB, were isolated from the thermophilic strain Bacillus coagulans K.

Environmental mapping based on spatial variability.

Environmental maps show the probable environmental states of different types of land use or development of landscape in a geographic context. Remotely sensed data are particularly efficient for environmental mapping in order to outline major environmental types. Multiple schemes of image classification used in environmental mapping are either traditionally statistical or heuristic.