2,960 research outputs found
Temporal inabilities and decision-making capacity in depression
We report on an interview-based study of decision-making capacity in two classes of patients suffering from depression. Developing a method of second-person hermeneutic phenomenology, we articulate the distinctive combination of temporal agility and temporal inability characteristic of the experience of severely depressed patients. We argue that a cluster of decision-specific temporal abilities is a critical element of decision-making capacity, and we show that loss of these abilities is a risk factor distinguishing severely depressed patients from mildly/moderately depressed patients. We explore the legal and clinical consequences of this result
Genomic structure and alternative splicing of murine R2B receptor protein tyrosine phosphatases (PTPÎș, ÎŒ, Ï and PCP-2)
BACKGROUND: Four genes designated as PTPRK (PTPÎș), PTPRL/U (PCP-2), PTPRM (PTPÎŒ) and PTPRT (PTPÏ) code for a subfamily (type R2B) of receptor protein tyrosine phosphatases (RPTPs) uniquely characterized by the presence of an N-terminal MAM domain. These transmembrane molecules have been implicated in homophilic cell adhesion. In the human, the PTPRK gene is located on chromosome 6, PTPRL/U on 1, PTPRM on 18 and PTPRT on 20. In the mouse, the four genes ptprk, ptprl, ptprm and ptprt are located in syntenic regions of chromosomes 10, 4, 17 and 2, respectively. RESULTS: The genomic organization of murine R2B RPTP genes is described. The four genes varied greatly in size ranging from ~64 kb to ~1 Mb, primarily due to proportional differences in intron lengths. Although there were also minor variations in exon length, the number of exons and the phases of exon/intron junctions were highly conserved. In situ hybridization with digoxigenin-labeled cRNA probes was used to localize each of the four R2B transcripts to specific cell types within the murine central nervous system. Phylogenetic analysis of complete sequences indicated that PTPÏ and PTPÎŒ were most closely related, followed by PTPÎș. The most distant family member was PCP-2. Alignment of RPTP polypeptide sequences predicted putative alternatively spliced exons. PCR experiments revealed that five of these exons were alternatively spliced, and that each of the four phosphatases incorporated them differently. The greatest variability in genomic organization and the majority of alternatively spliced exons were observed in the juxtamembrane domain, a region critical for the regulation of signal transduction. CONCLUSIONS: Comparison of the four R2B RPTP genes revealed virtually identical principles of genomic organization, despite great disparities in gene size due to variations in intron length. Although subtle differences in exon length were also observed, it is likely that functional differences among these genes arise from the specific combinations of exons generated by alternative splicing
Application of COMPOCHIP Microarray to Investigate the Bacterial Communities of Different Composts
A microarray spotted with 369 different 16S rRNA gene probes specific to microorganisms involved in the degradation process of organic waste during composting was developed. The microarray was tested with pure cultures, and of the 30,258 individual probe-target hybridization reactions performed, there were only 188 false positive (0.62%) and 22 false negative signals (0.07%). Labeled target DNA was prepared by polymerase chain reaction amplification of 16S rRNA genes using a Cy5-labeled universal bacterial forward primer and a universal reverse primer. The COMPOCHIP microarray was applied to three different compost types (green compost, manure mix compost, and anaerobic digestate compost) of different maturity (2, 8, and 16 weeks), and differences in the microorganisms in the three compost types and maturity stages were observed. Multivariate analysis showed that the bacterial composition of the three composts was different at the beginning of the composting process and became more similar upon maturation. Certain probes (targeting Sphingobacterium, Actinomyces, Xylella/Xanthomonas/ Stenotrophomonas, Microbacterium, Verrucomicrobia, Planctomycetes, Low G + C and Alphaproteobacteria) were more influential in discriminating between different composts. Results from denaturing gradient gel electrophoresis supported those of microarray analysis. This study showed that the COMPOCHIP array is a suitable tool to study bacterial communities in composts
Passive movement therapy in patients with moderate to severe paratonia; study protocol of a randomised clinical trial (ISRCTN43069940)
Contains fulltext :
65492.pdf ( ) (Open Access
Poly-acetylated chromatin signatures are preferred epitopes for site-specific histone H4 acetyl antibodies
Antibodies specific for histone post-translational modifications (PTMs) have been central to our understanding of chromatin biology. Here, we describe an unexpected and novel property of histone H4 site-specific acetyl antibodies in that they prefer poly-acetylated histone substrates. By all current criteria, these antibodies have passed specificity standards. However, we find these site-specific histone antibodies preferentially recognize chromatin signatures containing two or more adjacent acetylated lysines. Significantly, we find that the poly-acetylated epitopes these antibodies prefer are evolutionarily conserved and are present at levels that compete for these antibodies over the intended individual acetylation sites. This alarming property of acetyl-specific antibodies has far-reaching implications for data interpretation and may present a challenge for the future study of acetylated histone and non-histone proteins
Towards a large-scale quantum simulator on diamond surface at room temperature
Strongly-correlated quantum many-body systems exhibits a variety of exotic
phases with long-range quantum correlations, such as spin liquids and
supersolids. Despite the rapid increase in computational power of modern
computers, the numerical simulation of these complex systems becomes
intractable even for a few dozens of particles. Feynman's idea of quantum
simulators offers an innovative way to bypass this computational barrier.
However, the proposed realizations of such devices either require very low
temperatures (ultracold gases in optical lattices, trapped ions,
superconducting devices) and considerable technological effort, or are
extremely hard to scale in practice (NMR, linear optics). In this work, we
propose a new architecture for a scalable quantum simulator that can operate at
room temperature. It consists of strongly-interacting nuclear spins attached to
the diamond surface by its direct chemical treatment, or by means of a
functionalized graphene sheet. The initialization, control and read-out of this
quantum simulator can be accomplished with nitrogen-vacancy centers implanted
in diamond. The system can be engineered to simulate a wide variety of
interesting strongly-correlated models with long-range dipole-dipole
interactions. Due to the superior coherence time of nuclear spins and
nitrogen-vacancy centers in diamond, our proposal offers new opportunities
towards large-scale quantum simulation at room temperatures
On the renormalization of multiparton webs
We consider the recently developed diagrammatic approach to soft-gluon
exponentiation in multiparton scattering amplitudes, where the exponent is
written as a sum of webs - closed sets of diagrams whose colour and kinematic
parts are entangled via mixing matrices. A complementary approach to
exponentiation is based on the multiplicative renormalizability of intersecting
Wilson lines, and their subsequent finite anomalous dimension. Relating this
framework to that of webs, we derive renormalization constraints expressing all
multiple poles of any given web in terms of lower-order webs. We examine these
constraints explicitly up to four loops, and find that they are realised
through the action of the web mixing matrices in conjunction with the fact that
multiple pole terms in each diagram reduce to sums of products of lower-loop
integrals. Relevant singularities of multi-eikonal amplitudes up to three loops
are calculated in dimensional regularization using an exponential infrared
regulator. Finally, we formulate a new conjecture for web mixing matrices,
involving a weighted sum over column entries. Our results form an important
step in understanding non-Abelian exponentiation in multiparton amplitudes, and
pave the way for higher-loop computations of the soft anomalous dimension.Comment: 60 pages, 15 figure
Truncated and Helix-Constrained Peptides with High Affinity and Specificity for the cFos Coiled-Coil of AP-1
Protein-based therapeutics feature large interacting surfaces. Protein folding endows structural stability to localised surface epitopes, imparting high affinity and target specificity upon interactions with binding partners. However, short synthetic peptides with sequences corresponding to such protein epitopes are unstructured in water and promiscuously bind to proteins with low affinity and specificity. Here we combine structural stability and target specificity of proteins, with low cost and rapid synthesis of small molecules, towards meeting the significant challenge of binding coiled coil proteins in transcriptional regulation. By iteratively truncating a Jun-based peptide from 37 to 22 residues, strategically incorporating i-->i+4 helix-inducing constraints, and positioning unnatural amino acids, we have produced short, water-stable, alpha-helical peptides that bind cFos. A three-dimensional NMR-derived structure for one peptide (24) confirmed a highly stable alpha-helix which was resistant to proteolytic degradation in serum. These short structured peptides are entropically pre-organized for binding with high affinity and specificity to cFos, a key component of the oncogenic transcriptional regulator Activator Protein-1 (AP-1). They competitively antagonized the cJunâcFos coiled-coil interaction. Truncating a Jun-based peptide from 37 to 22 residues decreased the binding enthalpy for cJun by ~9 kcal/mol, but this was compensated by increased conformational entropy (TDS †7.5 kcal/mol). This study demonstrates that rational design of short peptides constrained by alpha-helical cyclic pentapeptide modules is able to retain parental high helicity, as well as high affinity and specificity for cFos. These are important steps towards small antagonists of the cJun-cFos interaction that mediates gene transcription in cancer and inflammatory diseases
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