Normal newt limb regeneration requires matrix metalloproteinase function

AbstractNewts regenerate lost limbs through a complex process involving dedifferentiation, migration, proliferation, and redifferentiation of cells proximal to the amputation plane. To identify the genes controlling these cellular events, we performed a differential display analysis between regenerating and nonregenerating limbs from the newt Notophthalmus viridescens. This analysis, coupled with a direct cloning approach, identified a previously unknown Notophthalmus collagenase gene (nCol) and three known matrix metalloproteinase (MMP) genes, MMP3/10a, MMP3/10b, and MMP9, all of which are upregulated within hours of limb amputation. MMP3/10b exhibits the highest and most ubiquitous expression and appears to account for the majority of the proteolytic activity in the limb as measured by gel zymography. By testing purified recombinant MMP proteins against potential substrates, we show that nCol is a true collagenase, MMP9 is a gelatinase, MMP3/10a is a stromelysin, and MMP3/10b has an unusually broad substrate profile, acting both as a stromelysin and noncanonical collagenase. Exposure of regenerating limbs to the synthetic MMP inhibitor GM6001 produces either dwarfed, malformed limb regenerates or limb stumps with distal scars. These data suggest that MMPs are required for normal newt limb regeneration and that MMPs function, in part, to prevent scar formation during the regenerative process

Method and Apparatus for Transferring a Person

A method and vehicle preferably a wheelchair (10) for transporting and transferring an invalid person is described. The wheelchair has first and second frames (12 and 48) with drive wheels (18) between which is provided a chair (82) or support (83). The first frame has top and bottom sliding mechanisms (34 and 36) which are mounted by I-beam extensions (38 and 40) to the bars (24 and 26) of the first frame. The second frame has top and bottom rails (54 and 56) which are slidably connected to the sliding mechanisms of the first frame. The rails have slots (78) through which extend the center portions (38C and 40C) of the extensions which allow the first frame to move along the length of the rails. The bottom rails have front wheels (60), intermediate wheels (68) and stabilizing wheels (70). The chair is connected to the second frame by belts (84) and ratchets (86) and has a lifting system (90). In use, the wheelchair is moved adjacent the open doorway (104) of the automotive vehicle (100) and the second frame with the chair and person are slid over the seat (102). As the second frame moves, the second frame tilts such that the intermediate wheels touch the ground surface (72). The seat is lowered using the ratchets and removed from the wheelchair

Cellular electroporation induces dedifferentiation in intact newt limbs

AbstractNewts have the remarkable ability to regenerate lost appendages including their forelimbs, hindlimbs, and tails. Following amputation of an appendage, the wound is rapidly closed by the migration of epithelial cells from the proximal epidermis. Internal cells just proximal to the amputation plane begin to dedifferentiate to form a pool of proliferating progenitor cells known as the regeneration blastema. We show that dedifferentiation of internal appendage cells can be initiated in the absence of amputation by applying an electric field sufficient to induce cellular electroporation, but not necrosis or apoptosis. The time course for dedifferentiation following electroporation is similar to that observed following amputation with evidence of dedifferentiation beginning at about 5 days postelectroporation and continuing for 2 to 3 weeks. Microarray analyses, real-time RT-PCR, and in situ hybridization show that changes in early gene expression are similar following amputation or electroporation. We conclude that the application of an electric field sufficient to induce transient electroporation of cell membranes induces a dedifferentiation response that is virtually indistinguishable from the response that occurs following amputation of newt appendages. This discovery allows dedifferentiation to be studied in the absence of wound healing and may aid in identifying genes required for cellular plasticity

LIM-kinase1 Hemizygosity Implicated in Impaired Visuospatial Constructive Cognition

AbstractTo identify genes important for human cognitive development, we studied Williams syndrome (WS), a developmental disorder that includes poor visuospatial constructive cognition. Here we describe two families with a partial WS phenotype; affected members have the specific WS cognitive profile and vascular disease, but lack other WS features. Submicroscopic chromosome 7q11.23 deletions cosegregate with this phenotype in both families. DNA sequence analyses of the region affected by the smallest deletion (83.6 kb) revealed two genes, elastin (ELN ) and LIM-kinase1 (LIMK1). The latter encodes a novel protein kinase with LIM domains and is strongly expressed in the brain. Because ELN mutations cause vascular disease but not cognitive abnormalities, these data implicate LIMK1 hemizygosity in impaired visuospatial constructive cognition

Understanding and assessing the impact of treatment in diabetes: the Treatment-Related Impact Measures for Diabetes and Devices (TRIM-Diabetes and TRIM-Diabetes Device)

<p>Abstract</p> <p>Purpose</p> <p>Diabetes is a debilitating illness requiring lifelong management. Treatments can be varied in terms of mode of administration as well as type of agent. Unfortunately, most patient reported outcome measures currently available to assess the impact of treatment are specific to diabetes type, treatment modality or delivery systems and are designed to be either a HRQoL or treatment satisfaction measure. To address these gaps, the Treatment Related Impact Measure-Diabetes and Device measures were developed. This paper presents the item development and validation of the TRIM Diabetes/Device.</p> <p>Methods</p> <p>Patient interviews were conducted to collect the patient perspective and ensure high content validity. Interviews were hand coded and qualitatively analyzed to identify common themes. A conceptual model of the impact of diabetes medication was developed and preliminary items for the TRIM-Diabetes/Device were generated and cognitively debriefed. Validation data was collected via an on-line survey and analyzed according to an a priori statistical analysis plan to validate the overall score as well as each domain. Item level criteria were used to reduce the preliminary item pool. Next, factor analysis to identify structural domains was performed. Reliability and validity testing was then performed.</p> <p>Results</p> <p>One hundred and five patients were interviewed in focus groups, individual interviews and for cognitive debriefing. Five hundred seven patients participated in the validation study. Factor analysis identified seven domains: Treatment Burden, Daily Life; Diabetes Management; Psychological Health; Compliance and Device Function and Bother. Internal consistency reliability coefficients of the TRIM-Diabetes/Device ranged from 0.80 and 0.94. Test-retest reliability of the TRIM-Diabetes/Device ranged from 0.71 to 0.89. All convergent and known groups validity hypotheses were met for the TRIM-Diabetes/Device total scores and sub-scales.</p> <p>Conclusion</p> <p>Validation is an ongoing and iterative process. These findings are the first step in that process and have shown that both the TRIM-Diabetes and the TRIM-Diabetes Device have acceptable psychometric properties. Future research is needed to continue the validation process and examine responsiveness and the validity of the TRIM-Diabetes/Device in a clinical trial population.</p

The Pattern of the Mineralization of Enamel

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/68291/2/10.1177_00220345610400050101.pd

The tyranny of the male preserve

Within this paper I draw on short vignettes and quotes taken from a two-year ethnographic study of boxing to think through the continuing academic merit of the notion of the male preserve. This is an important task due to evidence of shifts in social patterns of gender that have developed since the idea was first proposed in the 1970s. In aligning theoretical contributions from Lefebvre and Butler to discussions of the male preserve, we are able to add nuance to our understanding of how such social spaces are engrained with and produced by the lingering grasp of patriarchal narratives. In particular, by situating the male preserve within shifting social processes, whereby certain men’s power is increasingly undermined, I highlight the production of space within which narratives connecting men to violence, aggression and physical power can be consumed, performed and reified in a relatively unrestricted form. This specific case study contributes to gender theory as an illustration of a way in which we might explore and understand social enclaves where certain people are able to lay claim to space and power. As such, I argue that the notion of the male preserve is still a useful conceptual, theoretical and political device especially when considered as produced by the tyranny of gender power through the dramatic representation and reification of behaviours symbolically linked to patriarchal narrations of manhood

Measurement of the flavour composition of dijet events in pp collisions at root s=7 TeV with the ATLAS detector

This paper describes a measurement of the flavour composition of dijet events produced in pp collisions at &#8730;s=7 TeV using the ATLAS detector. The measurement uses the full 2010 data sample, corresponding to an integrated luminosity of 39 pb−1. Six possible combinations of light, charm and bottom jets are identified in the dijet events, where the jet flavour is defined by the presence of bottom, charm or solely light flavour hadrons in the jet. Kinematic variables, based on the properties of displaced decay vertices and optimised for jet flavour identification, are used in a multidimensional template fit to measure the fractions of these dijet flavour states as functions of the leading jet transverse momentum in the range 40 GeV to 500 GeV and jet rapidity |y|&#60;2.1. The fit results agree with the predictions of leading- and next-to-leading-order calculations, with the exception of the dijet fraction composed of bottom and light flavour jets, which is underestimated by all models at large transverse jet momenta. The ability to identify jets containing two b-hadrons, originating from e.g. gluon splitting, is demonstrated. The difference between bottom jet production rates in leading and subleading jets is consistent with the next-to-leading-order predictions

Observation of associated near-side and away-side long-range correlations in √sNN=5.02 TeV proton-lead collisions with the ATLAS detector

Two-particle correlations in relative azimuthal angle (Δϕ) and pseudorapidity (Δη) are measured in √sNN=5.02  TeV p+Pb collisions using the ATLAS detector at the LHC. The measurements are performed using approximately 1  μb-1 of data as a function of transverse momentum (pT) and the transverse energy (ΣETPb) summed over 3.1<η<4.9 in the direction of the Pb beam. The correlation function, constructed from charged particles, exhibits a long-range (2<|Δη|<5) “near-side” (Δϕ∼0) correlation that grows rapidly with increasing ΣETPb. A long-range “away-side” (Δϕ∼π) correlation, obtained by subtracting the expected contributions from recoiling dijets and other sources estimated using events with small ΣETPb, is found to match the near-side correlation in magnitude, shape (in Δη and Δϕ) and ΣETPb dependence. The resultant Δϕ correlation is approximately symmetric about π/2, and is consistent with a dominant cos⁡2Δϕ modulation for all ΣETPb ranges and particle pT

Search for R-parity-violating supersymmetry in events with four or more leptons in sqrt(s) =7 TeV pp collisions with the ATLAS detector

A search for new phenomena in final states with four or more leptons (electrons or muons) is presented. The analysis is based on 4.7 fb−1 of $\sqrt{s}=7\;\mathrm{TeV}$ proton-proton collisions delivered by the Large Hadron Collider and recorded with the ATLAS detector. Observations are consistent with Standard Model expectations in two signal regions: one that requires moderate values of missing transverse momentum and another that requires large effective mass. The results are interpreted in a simplified model of R-parity-violating supersymmetry in which a 95% CL exclusion region is set for charged wino masses up to 540 GeV. In an R-parity-violating MSUGRA/CMSSM model, values of m 1/2 up to 820 GeV are excluded for 10 < tan β < 40