Integrins (version 2019.4) in the IUPHAR/BPS Guide to Pharmacology Database

Integrins are unusual signalling proteins that function to signal both from the extracellular environment into the cell, but also from the cytoplasm to the external of the cell. The intracellular signalling cascades associated with integrin activation focus on protein kinase activities, such as focal adhesion kinase and Src. Based on this association between extracellular signals and intracellular protein kinase activity, we have chosen to include integrins in the 'Catalytic receptors' section of the database until more stringent criteria from NC-IUPHAR allows precise definition of their classification.Integrins are heterodimeric entities, composed of α and β subunits, each 1TM proteins, which bind components of the extracellular matrix or counter-receptors expressed on other cells. One class of integrin contains an inserted domain (I) in its α subunit, and if present (in α1, α2, α10, α11, αD, αE, αL, αM and αX), this I domain contains the ligand binding site. All β subunits possess a similar I-like domain, which has the capacity to bind ligand, often recognising the RGD motif. The presence of an α subunit I domain precludes ligand binding through the β subunit. Integrins provide a link between ligand and the actin cytoskeleton (through typically short intracellular domains). Integrins bind several divalent cations, including a Mg2+ ion in the I or I-like domain that is essential for ligand binding. Other cation binding sites may regulate integrin activity or stabilise the 3D structure. Integrins regulate the activity of particular protein kinases, including focal adhesion kinase and integrin-linked kinase. Cellular activation regulates integrin ligand affinity via inside-out signalling and ligand binding to integrins can regulate cellular activity via outside-in signalling.Several drugs that target integrins are in clinical use including: (1) abciximab (αIIbβ3) for short term prevention of coronary thrombosis, (2) vedolizumab (α4β7) to reduce gastrointestinal inflammation, and (3) natalizumab (α4β1) in some cases of severe multiple sclerosis

Integrins in GtoPdb v.2023.1

Integrins are unusual signalling proteins that function to signal both from the extracellular environment into the cell, but also from the cytoplasm to the external of the cell. The intracellular signalling cascades associated with integrin activation focus on protein kinase activities, such as focal adhesion kinase and Src. Based on this association between extracellular signals and intracellular protein kinase activity, we have chosen to include integrins in the 'Catalytic receptors' section of the database until more stringent criteria from NC-IUPHAR allows precise definition of their classification.Integrins are heterodimeric entities, composed of α and β subunits, each 1TM proteins, which bind components of the extracellular matrix or counter-receptors expressed on other cells. One class of integrin contains an inserted domain (I) in its α subunit, and if present (in α1, α2, α10, α11, αD, αE, αL, αM and αX), this I domain contains the ligand binding site. All β subunits possess a similar I-like domain, which has the capacity to bind ligand, often recognising the RGD motif. The presence of an α subunit I domain precludes ligand binding through the β subunit. Integrins provide a link between ligand and the actin cytoskeleton (through typically short intracellular domains). Integrins bind several divalent cations, including a Mg2+ ion in the I or I-like domain that is essential for ligand binding. Other cation binding sites may regulate integrin activity or stabilise the 3D structure. Integrins regulate the activity of particular protein kinases, including focal adhesion kinase and integrin-linked kinase. Cellular activation regulates integrin ligand affinity via inside-out signalling and ligand binding to integrins can regulate cellular activity via outside-in signalling.Several drugs that target integrins are in clinical use including: (1) abciximab (αIIbβ3) for short term prevention of coronary thrombosis, (2) vedolizumab (α4β7) to reduce gastrointestinal inflammation, and (3) natalizumab (α4β1) in some cases of severe multiple sclerosis

Method of joining two or more substrates with a seam

A method for joining two or more substrates with a seam is provided. The seam is formed with a thermoplastic tape that is capable of forming an adhesive bond and a physical bond with a substrate. For instance, in one embodiment, the thermoplastic tape is formed from a polyurethane film. In addition, the seam can be utilized in a flat configuration or folded into a variety of different shapes, such as in a z-shaped configuration. As a result of the present invention, it has been discovered that a seam can be formed to have improved strength without substantially sacrificing the desired functional properties of the substrate materials

The value of routine histopathological examination of appendicectomy specimens

<p>Abstract</p> <p>Background</p> <p>Appendicectomy specimens removed from patients with suspected acute appendicitis often appear macroscopically normal but histopathological analysis of these cases may reveal a more sinister underlying pathology. We evaluated histopathological reports of 1225 appendicectomy specimens at the Norfolk and Norwich University Hospital (NNUH) over the past three years.</p> <p>Methods</p> <p>Histopathology reports for all appendices analysed at the NNUH between March 2003 and March 2006 were reviewed by examination of the case notes. The analysis focussed on the confirmation of acute appendicitis, incidental unexpected incidental findings other than inflammation, whether these abnormalities were suspected on gross examination at the time of surgery, and the effect on patient management and prognosis.</p> <p>Results</p> <p>The histopathology reports disclosed a variety of abnormal incidental lesions. Of the 1225 specimens, 46 (3.75%) revealed abnormal diagnoses other than inflammatory changes. Twenty-four (1.96%) of these were clinically significant and affected further patient management. Only two of these (0.16%) were suspected on macroscopic examination intra-operatively.</p> <p>Conclusion</p> <p>Twenty-four of the 1225 specimens (1.96%) had an impact on patient management or outcome and were not suspected on macroscopic examination at the time of surgery. These would have been missed had the specimens not been examined microscopically. The intra-operative diagnosis of the surgeon is therefore unreliable in detecting abnormalities of the appendix. This study supports the sending of all appendicectomy specimens for routine histopathological examination.</p

Polynomial super-gl(n) algebras

We introduce a class of finite dimensional nonlinear superalgebras $L = L_{\bar{0}} + L_{\bar{1}}$ providing gradings of $L_{\bar{0}} = gl(n) \simeq sl(n) + gl(1)$. Odd generators close by anticommutation on polynomials (of degree $>1$) in the $gl(n)$ generators. Specifically, we investigate `type I' super-$gl(n)$ algebras, having odd generators transforming in a single irreducible representation of $gl(n)$ together with its contragredient. Admissible structure constants are discussed in terms of available $gl(n)$ couplings, and various special cases and candidate superalgebras are identified and exemplified via concrete oscillator constructions. For the case of the $n$-dimensional defining representation, with odd generators $Q_{a}, \bar{Q}{}^{b}$, and even generators ${E^{a}}_{b}$, $a,b = 1,...,n$, a three parameter family of quadratic super-$gl(n)$ algebras (deformations of $sl(n/1)$) is defined. In general, additional covariant Serre-type conditions are imposed, in order that the Jacobi identities be fulfilled. For these quadratic super-$gl(n)$ algebras, the construction of Kac modules, and conditions for atypicality, are briefly considered. Applications in quantum field theory, including Hamiltonian lattice QCD and space-time supersymmetry, are discussed.Comment: 31 pages, LaTeX, including minor corrections to equation (3) and reference [60

Marketing Aspects of Range Sheep Production in Texas.

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Molecular Gas in Candidate Double Barred Galaxies III. A Lack of Molecular Gas?

Most models of double-barred galaxies suggest that a molecular gas component is crucial for maintaining long-lived nuclear bars. We have undertaken a CO survey in an attempt to determine the gas content of these systems and to locate double barred galaxies with strong CO emission that could be candidates for high resolution mapping. We observed 10 galaxies in CO J=2-1 and J=3-2 and did not detect any galaxies that had not already been detected in previous CO surveys. We preferentially detect emission from galaxies containing some form of nuclear activity. Simulations of these galaxies require that they contain 2% to 10% gas by mass in order to maintain long-lived nuclear bars. The fluxes for the galaxies for which we have detections suggest that the gas mass fraction is in agreement with these models requirements. The lack of emission in the other galaxies suggests that they contain as little as 7 x 10^6 solar masses of molecular material which corresponds to < 0.1% gas by mass. This result combined with the wide variety of CO distributions observed in double barred galaxies suggests the need for models of double-barred galaxies that do not require a large, well ordered molecular gas component.Comment: 17 pages (3 figures embedded on pg 17). To appear in the March 10 issue of the Astrophysical Journa

Frequent grazing by sheep reduced caucasian clover cover and rhizome mass in ryegrass pasture

The responses of hexaploid caucasian clover (Trifolium ambiguum) to four contrasting grazing regimes were compared with those of white clover (T. repens) in an endophytic (Neotyphodium lolii) hybrid ryegrass pasture on a fertile lowland site. After 2 years, frequent grazing (set stocking) by sheep reduced caucasian clover cover to 10% compared with 25.5% in infrequent grazing (rotational grazing) treatments (mean spelling time 25 days). Similarly, frequent grazing reduced caucasian clover rhizome plus root dry weight (780 kg DM/ha when sampled to 100 mm depth in frequently grazed plots, compared with 3220 kg DM/ha for infrequent). Under frequent grazing treatments, mean white clover cover was 21%, under infrequent hard grazing it was 26% and under lax infrequent grazing it was 14%. The reduction in ryegrass tiller population from 5720/m² in the infrequently and laxly grazed treatments to 4150/ m² in the frequently hard grazed pastures indicated the severity of that hard grazed treatment. These results show that in lowland ryegrass pastures on high fertility sites, the stoloniferous growth form of white clover may be superior to the rhizomatous strategy of caucasian clover when grazing by sheep is frequent throughout spring, summer and autumn