Precision medicine

Although the microbiome is established as an important regulator of health and disease, the role of viruses that inhabit asymptomatic humans (collectively, the virome) is less defined. While we are still characterizing what constitutes a healthy or diseased virome, an exciting next step is to move beyond correlations and toward identification of specific viruses and their precise mechanisms of beneficial or harmful immunomodulation.

3p vibransone 28-03-2024 3 2   Download

Microsatellite instability (MSI) is a key marker for predicting the response of immune checkpoint inhibitors (ICIs) and for screening Lynch syndrome (LS). Aim: This study aimed to see the characteristics of cancers with high level of MSI (MSI-H) in genetic medicine and precision medicine.

12p vielonmusk 21-01-2022 10 0   Download

Precision medicine promises to improve both the efficacy and safety of therapeutic products by better informing why some patients respond well to a drug, and some experience adverse reactions, while others do not. Pharmacogenomics is a key component of precision medicine and can be utilized to select optimal doses for patients, more precisely identify individuals who will respond to a treatment and avoid serious drug-related toxicities.

5p caothientrangnguyen 09-05-2020 11 2   Download

Aralar1 and citrin are members of the subfamily of calciumbinding mitochondrial carriers and correspond to two isoforms of the mitochondrial aspartate/glutamate carrier (AGC). These proteins are activated by Ca2+ acting on the external side of the inner mitochondrial membrane. Although it is known that aralar1 is expressed mainly in skeletal muscle, heart and brain, whereas citrin is present in liver, kidney and heart, the precise tissue distribution of the two proteins in embryonic and adult tissues is largely unknown....

8p system191 01-06-2013 34 4   Download

The solution structure of the growth factor chimera mEGF/ TGFa44250 has been determined using an extended version of the DYANA procedure for calculating structures from NMR data. The backbone fold and preferred orientation of the domains of the chimera are similar to those found in previous studies of EGF structures, and several H-bonds used as input constraints in those studies were found independently in the chimera. This shows that the modified activity of the chimera does not result from a major structural change.

9p system191 01-06-2013 45 4   Download

During the development of multicellular organisms, both transient and stable gene expression patterns have to be established in a precisely orchestrated sequence. Evidence from diverse model organisms indicates that this epigenetic program involves not only transcription factors, but also the local structure, composition, and modification of chromatin, which define and maintain the accessibility and transcriptional competence of the nucleosomal DNA template.

6p research12 01-06-2013 33 4   Download

Conventional and saturation transfer electron paramagnetic resonance spectroscopy (EPR and ST EPR) was used to study the orientation of probe molecules in muscle fibers in different intermediate states of the ATP hydrolysis cycle. A separate procedure was used to obtain ST EPR spectra with precise phase settings even in the case of samples with low spectral intensity. Fibers prepared from rabbit psoas muscle were labeled with isothiocyanate spin labels at the reactive thiol sites of the catalytic domain of myosin....

10p research12 01-06-2013 38 6   Download

The mitogen activated protein (MAP) kinase module: (Raf fiMEKfiERKs) is central to the control of cell growth, cell differentiation and cell survival. The fidelity of signalling and the spatio-temporal activation are key deter-minants in generating precise biological responses. The fidelity is ensured by scaffold proteins – protein kinase
insulators – andby specific docking sites. The duration and the intensity of the response are in part controlled by the compartmentalization of the signalling molecules. ...

9p tumor12 20-04-2013 30 2   Download

High-resolution crystal structures of large ribosomal subunits from Deinococcus radioduranscomplexed with tRNA-mimics indicate that precise substrate positioning, mandatory for efficient protein biosynthesis with no further conformational rearrangements, is governed by remote interactions of the tRNA helical features.

14p fptmusic 16-04-2013 41 3   Download

Ca 2+ and cAMP are ubiquitous second messengers in euk-aryotes and control numerous physiological responses ran-ging fromfertilization to cell death induction 1 . Todistinguish between these different responses, their subtle regulation in time, space and amplitude is needed. Therefore, the char-acterization of the signalling process requires measurement of secondmessengers with tools of precise localization, high dynamic range and as little disturbance of cell physiology as possible.

10p fptmusic 16-04-2013 41 4   Download

Serpins are the largest family of protease inhibitors and are fundamental for the control of proteolysis in multicellular eukaryotes. Most eukaryote serpins inhibit serine or cysteine proteases, however, noninhibitory mem-bers have been identified that perform diverse functions in processes such as hormone delivery and tumour metastasis. More recently inhibitory ser-pins have been identified in prokaryotes and unicellular eukaryotes, never-theless, the precise molecular targets of these molecules remains to be identified....

6p fptmusic 12-04-2013 36 2   Download

In humans, eight types of histone H1 exist (H1.1–H1.5, H1
, H1t and H1oo), all consisting of a highly conserved globular domain and less con-served N- and C-terminal tails. Although the precise functions of these iso-forms are not yet understood, and H1 subtypes have been found to be dispensable for mammalian development, it is now clear that specific func-tions may be assigned to certain individual H1 subtypes.

11p fptmusic 11-04-2013 25 1   Download

External quality assessment schemes are evaluated by method-dependent consensus values or by method independent target values, determined with reference measurement procedures. The reference measurement procedures yield values having a high trueness and precision with a defined uncertainty of measure-ment. The great advantage of the reference measurement proce-dure is that the comparability of results in the different medical laboratories is promoted and improved intending in the same ref-erence interval for an analyte in all laboratories. ...

31p fptmusic 11-04-2013 47 3   Download

The male seahorse incubates its young in a manner resembling that of a mammalian pregnancy. After the female deposits her eggs into the male’s brood pouch they are fertilized and the embryos develop and grow for several weeks until they are able to withstand the external environmental conditions independently, at which point they are irreversibly released. Although the precise function of the brood pouch is not clear, it is probably related to pro-viding a suitable protective and osmotic environment for the young. ...

15p awards 06-04-2013 28 3   Download

The AAA-peroxins Pex1p and Pex6p play a critical role in peroxisome bio-genesis but their precise function remains to be established. These two peroxins consist of three distinct regions (N, D1, D2), two of which (D1, D2) contain a conserved
230 amino acid cassette, which is common to all ATPases associated with various cellular activities (AAA). Here we show that Pex1p and Pex6p from Saccharomyces cerevisiaedo interact in vivo. We assigned their corresponding binding sites and elucidated the importance of ATP-binding and -hydrolysis of Pex1p and Pex6p for their interaction. ...

12p awards 05-04-2013 43 3   Download

Phospholipase D (PLD) plays amajor role in the activation of the neutrophil respiratory burst. However, the repertoire of PLD isoforms present in these primary cells, the precise mechanism of activation, andthe impact of cell priming on PLD activity and localization remain poorly defined. RT-PCR analysis showedthat both PLD1 andPLD2 iso-forms are expressedin human neutrophils, with PLD1 expressedat a higher level. Endogenous PLD1 was detected by immunoprecipitation andWestern blotting, andwas predominantly membrane-associated under control and primed/stimulated conditions....

10p dell39 03-04-2013 37 3   Download

During DNA replication, transcription and DNA repair in eukaryotes, the cellular machineries performing these tasks need to gain access to the DNA that is packaged into chromatin in the nucleus.Chromatin is a dynamic structure thatmodulates the access of regulatory factors to the genetic material.A precise coordination and organization of events in opening and closing of the chromatin is crucial to ensure that the correct spatial and temporal epigenetic code is maintained within the eukaryotic genome....

15p dell39 03-04-2013 42 4   Download

Why do proteins adopt the conformations that they do, and what determines their stabilities? While we have come to some understandingof the forces that underlie protein architecture, a precise, predictive, physicochemical explanation is still elusive. Two obstacles to addressing these questions are the unfathomable vastness of protein sequence space, and the difficulty in makingdirect phy-sical measurements on large numbers of protein variants. Here, we review combinatorial methods that have been applied to problems in protein biophysics over the last 15 years.

14p dell39 03-04-2013 58 3   Download

A role for the nuclear receptor peroxisome proliferator-activated recep-tor-b(PPARb) in oncogenesis has been suggested by a number of obser-vations but its precise role remains elusive. Prostaglandin I2 (PGI2 , prostacyclin), a major arachidonic acid (AA) derived cyclooxygenase (Cox) product, has been proposed as a PPARbagonist.

10p dell39 27-03-2013 40 3   Download

High-quality quantitative data generated under standardized conditions is critical for understanding dynamic cellular processes. We report strategies for error reduction, and algorithms for automated data processing and for establishing the widely used techniques of immunoprecipitation and immu-noblotting as highly precise methods for the quantification of protein levels and modifications.

12p dell39 27-03-2013 53 3   Download