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At least 685 records · Page 38Linked to original sources
PubMed2003

Identification of HLA-B27-restricted peptides in reactive arthritis and other spondyloarthropathies: computer algorithms and fluorescent activated cell sorting analysis as tools for hunting of HLA-B27-restricted chlamydial and autologous crossreactive peptides involved in reactive arthritis and ankylosing spondylitis.

The illustrated clinical and experimental results demonstrate the strong relationship between the MHC class I antigen HLA-B27 and synovial CD8+ T cells with specificity for bacterial and possible self-antigen in SpA. These new aspects obtained in recent experimental and clinical studies might also provide clues to the pathomechanisms of joint inflammation in SpA. In particular, the newly developed techniques will be of great relevance in the near future. New and more precise bioalgorithms reflecting new insights in the biology and biochemistry of proteins as recently presented [98, 99] can be helpful (e.g., a program with an improved prediction of the features of immunoproteasomes). Intracellular and secreted cytokine staining by FACScan allows examination of a great number of cells expressing certain antigens in response to certain stimuli. The analysis of T-cell responses with tetramer/peptide complexes can be useful to screen tissue sections for TCR, recognizing foreign or self-derived epitopes on those complexes loaded with selected (e.g., bacterial) peptides. Identification of arthritogenic peptides and a further understanding of the immunology of the pathomechanisms in SpA might open ways to design new peptide vaccines to prevent inflammation, autoimmunity, and other diseases by early intervention [100].

Algorithms↗
PubMed2002

Hunting for excitement: NMDA receptors in Huntington's disease.

Excitotoxic cell death stimulated by quinolinic acid injection into the striatum has a long history of "mimicking" many aspects of motor, behavioral, and neurochemical changes observed in Huntington's disease patients. In this issue of Neuron, provide insight into the role of NMDA receptors in the cell-specific excitotoxic death observed in Huntington's disease (HD) using a HD mouse model expressing full-length mutant huntingtin (htt).

Animals↗
PubMed2003

Intracellular Ca2+ signaling and human disease: the hunt begins with Huntington's.

Huntingtin, a protein altered by polyglutamine expansion in Huntington's disease (Httexp), forms a signaling complex with the InsP3R, an intracellular calcium channel, and Htt-associated protein 1A (HAP1A). The addition of Httexp increases the InsP3R sensitivity to InsP3, which subsequently makes neurons hyperresponsive to stimulation and presumably more prone to neurodegenerative processes.

Animals↗
PubMed2002

Genomic scale mutant hunt identifies cell size homeostasis genes in S. cerevisiae.

BACKGROUND: In most eukaryotic cells, there is a relationship between cell size and proliferative capacity. For example, in order to commit to cell division, the yeast Saccharomyces cerevisiae must attain a "critical cell size." This mechanism coordinates growth with cell division to maintain cell size homeostasis. Because very few cell size control genes are known, the genetic pathways responsible for cell size homeostasis remain obscure. Furthermore, elucidation of the mechanism of cell size homeostasis has been recalcitrant to genetic analysis primarily due to the difficulty in cloning cell size control genes. RESULTS: To identify new size control genes, the effect of 5958 single gene deletions (4792 homozygous and 1166 heterozygous gene deletions) on cell size in yeast grown to saturation was systematically determined. From these data, 49 genes were identified that dramatically altered cell size. Of these, 34 are involved in transcription, signal transduction, or cell cycle control; 88% of these genes have putative human homologs. Sixteen genes regulate cell size in a dosage-dependent manner, and the majority of mutants identified fail to correctly exit the cell cycle. Many of these genes are components of Ccr4-Not transcriptional complexes or function in the PKC-MAP kinase pathway. These genes may modulate cell size by altering the expression or activity of G1-phase cyclins. CONCLUSIONS: These results illustrate how systematic genetic screens can be used to dissect intricate biological processes that are refractory to classic genetic approaches. This genomic-wide genetic screen yielded 46 new cell size mutants and systematically assessed the effect of 5958 single gene deletions on cell size as cells exited the cell cycle.

Cell Cycle↗
PubMed2003

The hunt for huntingtin function: interaction partners tell many different stories.

Huntington's disease (HD) is a neurodegenerative disorder caused by an abnormally elongated polyglutamine (polyQ) tract in the large protein huntingtin (htt). Currently, both the normal function of htt in neurons and the molecular mechanism by which the expanded polyQ sequence in htt causes selective neurodegeneration remain elusive. Research in past years has identified several htt-interacting proteins such as htt-interacting protein 1, Src homology region 3-containing Grb2-like protein 3, protein kinase C and casein kinase substrate in neurons 1, htt-associated protein 1, postsynaptic density-95, FIP-2 (for 14.7K-interacting protein), specificity protein 1 and nuclear receptor co-repressor. These proteins play roles in clathrin-mediated endocytosis, apoptosis, vesicle transport, cell signalling, morphogenesis and transcriptional regulation, suggesting that htt is also involved in these processes.

Amino Acid Sequence↗
PubMed1999

Hunting for sacred cows.

"Sacred cows" are behavioral patterns that we continue to use even though they may no longer be effective. Their continued use tramples creativity, reduces innovative thought, limits the ability to respond quickly to change, and ultimately becomes costly to individuals and organizations. In less turbulent times, sacred cows were a source of irritation that managers worked around. There is no longer time available for managers to "work around" sacred cows. They must be rounded up and dealt with. It is only by confronting their own sacred cows that nurse managers will find the energy to maintain a caring environment for patients' families and staff.

Attitude of Health Personnel↗
PubMed2004

Horse injuries and racing practices in National Hunt racehorses in the UK: the results of a prospective cohort study.

A prospective cohort study was conducted on horses starting in hurdle and steeplechase races on six UK racecourses in 2000 and 2001. Trainers or carers were questioned on the horses' pre-race routine and observational data were collected in the stables and parade ring. Some practices were common to many starters, such as withholding food and water before racing whereas other practices, such as schooling frequency, were more variable. There was a total of 2879 starts and a total of 83 injuries or medical events (28.8/1000 starts). The commonest types of injury were tendon/suspensory injuries and lacerations/wounds. Multivariable logistic regression models were used to identify the relationship between predictor variables and the risk of injury. Risk of injury or medical event was associated with distance of the race and weight carried. The risk of injury, excluding medical events, was associated with the speed of the race and foot conformation.

Animal Husbandry↗
PubMed2003

Environmental tolerances of an invasive terrestrial amphipod, Arcitalitrus dorrieni (Hunt) in Britain.

We investigated key physiological tolerances of the invasive euterrestrial talitrid amphipod (or landhopper) Arcitalitrus dorrieni; desiccation, salt, high and low temperatures. The critical relative humidity below which, A. dorrieni experiences desiccation stress is very high (95-100%), making it completely reliant on the leaflitter/soil microhabitat. It is tolerant of a wide range of (sea) salt concentrations (5-750 mOsmol l(-1)) but is extremely vulnerable below 5 mOsmol l(-1). A. dorrieni does not tolerate low temperatures with a mean lower limit of 1.4 degrees C, but with no individual surviving <0 degrees C. The range of upper thermal tolerance (30-37.3 degrees C) was similar to that found for other landhopper and beachflea species. Based on its tolerance to these environmental factors it is suggested that A. dorrieni has a limited potential to invade further into Britain, being restricted to areas with sufficiently high ion concentrations and mild winters.

Acclimatization↗
PubMed2006

The Sir David Cuthbertson Medal Lecture. Hunting for new pieces to the complex puzzle of obesity.

Disentangling the neuroendocrine systems that regulate energy homeostasis and adiposity has been a long-standing challenge in pathophysiology, with obesity being an increasingly important public health problem. Adipose tissue is no longer considered a passive bystander in body-weight regulation. It actively secretes a large number of hormones, growth factors, enzymes, cytokines, complement factors and matrix proteins, at the same time as expressing receptors for most of these elements, which influence fuel storage, mobilisation and utilisation at both central and peripheral sites. Thus, an extensive cross talk at a local and systemic level in response to specific external stimuli or metabolic changes underpins the multifunctional characteristics of adipose tissue. In addition to the already-known adipokines, such as IL, TNFalpha, leptin, resistin and adiponectin, more recently attention has been devoted to 'newcomers' to the 'adipose tissue arena', which include aquaporin, caveolin, visfatin, serum amyloid A and vascular endothelial growth factor. While in vitro and in vivo experiments have provided extremely valuable information, the advances in genomics, proteomics and metabolomics are offering a level of information not previously attainable to help unlock the molecular basis of obesity. The potential and power of combining pathophysiological observations with the wealth of information provided by the human genome, knock-out models, transgenesis, DNA microarrays, RNA silencing and other emerging technologies offer a new and unprecedented view of a complex disease, conferring novel insights into old questions by identifying new pieces to the unfinished jigsaw puzzle of obesity.

Adipocytes↗