Reversible Photocontrol of Deoxyribozyme-Catalyzed RNA Cleavage under Multiple-Turnover Conditions

Lights, camera, action! Photoswitchable nucleoside analogues containing o-, m-, or p-azobenzenes can be inserted in the catalytic core of RNA-cleaving 10-23 deoxyribozymes by replacing a nonconserved residue (see picture). Irradiation of the modified deoxyribozymes at 366 nm enhances RNA cleavage rates up to ninefold, thus achieving the rates observed for the unmodified deoxyribozyme.

Selection Power and Selection Labor for Information Retrieval

This study examines the relation between selection power and selection labor for information retrieval (IR). It is the first part of the development of a labor theoretic approach to IR. Existing models for evaluation of IR systems are reviewed and the distinction of operational from experimental systems partly dissolved. The often covert, but powerful, influence from technology on practice and theory is rendered explicit. Selection power is understood as the human ability to make informed choices between objects or representations of objects and is adopted as the primary value for IR. Selection power is conceived as a property of human consciousness, which can be assisted or frustrated by system design. The concept of selection power is further elucidated, and its value supported, by an example of the discrimination enabled by index descriptions, the discovery of analogous concepts in partly independent scholarly and wider public discourses, and its embodiment in the design and use of systems. Selection power is regarded as produced by selection labor, with the nature of that labor changing with different historical conditions and concurrent information technologies. Selection labor can itself be decomposed into description and search labor. Selection labor and its decomposition into description and search labor will be treated in a subsequent article, in a further development of a labor theoretic approach to information retrieval.

CD33 reponses are blocked by SOCS3 through accelerated proteasomal-mediated turnover

CD33 is a member of the sialic acid–binding immunoglobulin-like lectin (Siglec) family of inhibitory receptors and a therapeutic target for acute myeloid leukemia (AML). CD33 contains a cytoplasmic immunoreceptor tyrosine-based inhibitory motif (ITIM), which can recruit SHP-1 and SHP-2. How CD33 expression is regulated is unclear. Suppressor of cytokine signaling 3 (SOCS3) is expressed in response to cytokines, LPS, and other PAMPs, and competes with SHP-1/2 binding to ITIMs of cytokine receptors, thereby inhibiting signaling. In this study, using peptide pull-down experiments, we found that SOCS3 can specifically bind to the phosphorylated ITIM of CD33. Additionally, following cross-linking SOCS3 can recruit the ECS E3 ligase resulting in accelerated proteasomal degradation of both CD33 and SOCS3. Our data suggest that the tyrosine motifs in CD33 are not important for internalization, while they are required for degradation. Moreover, SOCS3 inhibited the CD33-induced block on cytokine-induced proliferation. This is the first receptor shown to be degraded by SOCS3 and where SOCS3 and its target protein are degraded concomitantly. Our findings clearly suggest that during an inflammatory response, the inhibitory receptor CD33 is lost by this mechanism. Moreover, this has important clinical implications as tumors expressing SOCS3 may be refractory to -CD33 therapy.

Neuropeptide Y Y(1) receptor regulates protein turnover and constitutive gene expression in hypertrophying cardiomyocytes.

Increased levels of neuropeptide Y correlate with severity of left ventricular hypertrophy in vivo. At cardiomyocyte level, hypertrophy is characterised by increased mass and altered phenotype. The aims were to determine the contributions of increased synthesis and reduced degradation of protein to neuropeptide Y-mediated increase in mass, assess effects on gene expression, and characterise neuropeptide Y Y receptor subtype involvement. Neuropeptide Y (10 nM) increased protein mass of adult rat ventricular cardiomyocytes maintained in culture (24 h) (16%>basal) and de novo protein synthesis (incorporation of [14C]phenylalanine) (18%>basal). Neuropeptide Y (100 nM) prevented degradation of existing protein at 8 h. Actinomycin D (5 µM) attenuated increases in protein mass to neuropeptide Y (=1 nM) but not to neuropeptide Y (10 nM). [Leu31, Pro34]neuropeptide Y (10 nM), an agonist at neuropeptide Y Y1 receptors, increased protein mass (25%>basal) but did not stimulate protein synthesis. Neuropeptide Y-(3–36) (10 nM), an agonist at neuropeptide Y Y2 receptors, increased protein mass (29%>basal) and increased protein synthesis (13%>basal), respectively. Actinomycin D (5 µM) abolished the increase in protein mass elicited by neuropeptide Y-(3–36) but not that by [Leu31, Pro34]neuropeptide Y. BIBP3226 [(R)-N2-(diphenylacetyl)-N-(4-hydroxyphenylmethyl)-d-arginine amide] (1 µM), a neuropeptide Y Y1 receptor subtype-selective antagonist, and T4 [neuropeptide Y-(33–36)]4, a neuropeptide Y Y2 receptor subtype-selective antagonist, attenuated the increase in protein mass to 100 nM neuropeptide Y by 68% and 59%, respectively. Neuropeptide Y increased expression of the constitutive gene, myosin light chain-2 (MLC-2), maximally at 12 h (4.7-fold>basal) but did not induce (t=36 h) expression of foetal genes (atrial natriuretic peptide (ANP), skeletal-a-actin and myosin heavy chain-ß). This increase was attenuated by 86% and 51%, respectively, by BIBP3226 (1 µM) and T4 [neuropeptide Y-(33–36)]4 (100 nM). [Leu31, Pro34]neuropeptide Y (100 nM) (2.4-fold>basal) and peptide YY-(3–36) (100 nM) (2.3 fold>basal) increased expression of MLC-2 mRNA at 12 h. In conclusion, initiation of cardiomyocyte hypertrophy by neuropeptide Y requires activation of both neuropeptide Y Y1 and neuropeptide Y Y2 receptors and is associated with enhanced synthesis and attenuated degradation of protein together with increased expression of constitutive genes but not reinduction of foetal genes.

Description and search labor for information retrieval

Selection power is taken as the fundamental value for information retrieval systems. Selection power is regarded as produced by selection labor, which itself separates historically into description and search labor. As forms of mental labor, description and search labor participate in the conditions for labor and for mental labor. Concepts and distinctions applicable to physical and mental labor are indicated, introducing the necessity of labor for survival, the idea of technology as a human construction, and the possibility of the transfer of human labor to technology. Distinctions specific to mental labor, particular between semantic and syntactic labor, are introduced. Description labor is exemplified by cataloging, classification, and database description, can be more formally understood as the labor involved in the transformation of objects for description into searchable descriptions, and is also understood to include interpretation. The costs of description labor are discussed. Search labor is conceived as the labor expended in searching systems. For both description and search labor, there has been a progressive reduction in direct human labor, with its syntactic aspects transferred to technology, effectively compelled by the high relative costs of direct human labor compared to machine processes.

A labor theoretic approach to information retrieval

This article synthesizes the labor theoretic approach to information retrieval. Selection power is taken as the fundamental value for information retrieval and is regarded as produced by selection labor. Selection power remains relatively constant while selection labor modulates across oral, written, and computational modes. A dynamic, stemming principally from the costs of direct human mental labor and effectively compelling the transfer of aspects of human labor to computational technology, is identified. The decision practices of major information system producers are shown to conform with the motivating forces identified in the dynamic. An enhancement of human capacities, from the increased scope of description processes, is revealed. Decision variation and decision considerations are identified. The value of the labor theoretic approach is considered in relation to pre-existing theories, real world practice, and future possibilities. Finally, the continuing intractability of information retrieval is suggested.

Labor and Place: The Contours of Freedpeoples' Mobilization in Reconstruction South Carolina

Important advances in scholarship on the post-emancipation South have made possible a new synthesis that moves beyond broad generalizations about African American agency to identify both the shared elements in black life across the region and the varying capacity of freedpeople to assert their interests in the face of white hostility. Building on a number of recent studies of Reconstruction this article seeks to demonstrate that the varying capacity of freedpeople in South Carolina to shape and defend the new society that would emerge after the end of slavery was rooted in their relative strength at work and in their communities. In Charleston and its lowcountry rural hinterland, demographic strength combined with deeply-rooted traditions of collective assertion to sustain a remarkably vibrant grassroots movement that persisted beyond the overthrow of Reconstruction. From very early on, by contrast, former slaves dispersed across the rural interior found their freedom severely circumscribed by a bellicose and heavily-armed white paramilitary campaign.