Pathfinder cells provide a novel therapeutic intervention for acute kidney injury

Pathfinder cells (PCs) are a novel class of adult-derived cells that facilitate functional repair of host tissue. We used rat PCs to demonstrate that they enable the functional mitigation of ischemia reperfusion (I/R) injury in a mouse model of renal damage. Female C57BL/6 mice were subjected to 30 min of renal ischemia and treated with intravenous (i.v.) injection of saline (control) or male rat pancreas-derived PCs in blinded experimentation. Kidney function was assessed 14 days after treatment by measuring serum creatinine (SC) levels. Kidney tissue was assessed by immunohistochemistry (IHC) for markers of cellular damage, proliferation, and senescence (TUNEL, Ki67, p16ink4a, p21). Fluorescence in situ hybridization (FISH) was performed to determine the presence of any rat (i.e., pathfinder) cells in the mouse tissue. PC-treated animals demonstrated superior renal function at day 14 post-I/R, in comparison to saline-treated controls, as measured by SC levels (0.13 mg/dL vs. 0.23 mg/dL, p<0.001). PC-treated kidney tissue expressed significantly lower levels of p16ink4a in comparison to the control group (p=0.009). FISH analysis demonstrated that the overwhelming majority of repaired kidney tissue was mouse in origin. Rat PCs were only detected at a frequency of 0.02%. These data confirm that PCs have the ability to mitigate functional damage to kidney tissue following I/R injury. Kidneys of PC-treated animals showed evidence of improved function and reduced expression of damage markers. The PCs appear to act in a paracrine fashion, stimulating the host tissue to recover functionally, rather than by differentiating into renal cells. This study demonstrates that pancreatic-derived PCs from the adult rat can enable functional repair of renal damage in mice. It validates the use of PCs to regenerate damaged tissues and also offers a novel therapeutic intervention for repair of solid organ damage in situ

Plasma Wave Properties of the Schwarzschild Magnetosphere in a Veselago Medium

We re-formulate the 3+1 GRMHD equations for the Schwarzschild black hole in a Veselago medium. Linear perturbation in rotating (non-magnetized and magnetized) plasma is introduced and their Fourier analysis is considered. We discuss wave properties with the help of wave vector, refractive index and change in refractive index in the form of graphs. It is concluded that some waves move away from the event horizon in this unusual medium. We conclude that for the rotating non-magnetized plasma, our results confirm the presence of Veselago medium while the rotating magnetized plasma does not provide any evidence for this medium.Comment: 20 pages, 15 figures, accepted for publication in Astrophys. Space Sc

An RB-EZH2 Complex Mediates Silencing of Repetitive DNA Sequences

Repetitive genomic regions include tandem sequence repeats and interspersed repeats, such as endogenous retroviruses and LINE-1 elements. Repressive heterochromatin domains silence expression of these sequences through mechanisms that remain poorly understood. Here, we present evidence that the retinoblastoma protein (pRB) utilizes a cell-cycle-independent interaction with E2F1 to recruit enhancer of zeste homolog 2 (EZH2) to diverse repeat sequences. These include simple repeats, satellites, LINEs, and endogenous retroviruses as well as transposon fragments. We generated a mutant mouse strain carrying an F832A mutation in Rb1 that is defective for recruitment to repetitive sequences. Loss of pRB-EZH2 complexes from repeats disperses H3K27me3 from these genomic locations and permits repeat expression. Consistent with maintenance of H3K27me3 at the Hox clusters, these mice are developmentally normal. However, susceptibility to lymphoma suggests that pRB-EZH2 recruitment to repetitive elements may be cancer relevant

Living for the weekend: youth identities in northeast England

Consumption and consumerism are now accepted as key contexts for the construction of youth identities in de-industrialized Britain. This article uses empirical evidence from interviews with young people to suggest that claims of `new community' are overstated, traditional forms of friendship are receding, and increasingly atomized and instrumental youth identities are now being culturally constituted and reproduced by the pressures and anxieties created by enforced adaptation to consumer capitalism. Analysis of the data opens up the possibility of a critical rather than a celebratory exploration of the wider theoretical implications of this process

Isothermal Plasma Wave Properties of the Schwarzschild de-Sitter Black Hole in a Veselago Medium

In this paper, we study wave properties of isothermal plasma for the Schwarzschild de-Sitter black hole in a Veselago medium. We use ADM 3+1 formalism to formulate general relativistic magnetohydrodynamical (GRMHD) equations for the Schwarzschild de-Sitter spacetime in Rindler coordinates. Further, Fourier analysis of the linearly perturbed GRMHD equations for the rotating (non-magnetized and magnetized) background is taken whose determinant leads to a dispersion relation. We investigate wave properties by using graphical representation of the wave vector, the refractive index, change in refractive index, phase and group velocities. Also, the modes of wave dispersion are explored. The results indicate the existence of the Veselago medium.Comment: 24 pages, 12 figures, accepted for publication in Astrophys. Space Sci. arXiv admin note: text overlap with arXiv:1101.0884 and arxiv:1007.285

Predictors of Medical Serious Adverse Events in Hip Fracture Patients Treated With Arthroplasty

AIM: Patients with hip fractures are often frail with multiple comorbidities and at risk of medical serious adverse events (SAEs). We investigated the HEALTH trial patient population to ascertain predictors of SAEs. METHODS: We performed a multivariable Cox regression analysis. Occurrence of SAEs was included as the dependent variable with 31 potential prognostic factors being included as independent variables. RESULTS: One thousand four hundred forty-one patients were included in this analysis. Three hundred seventy (25.6%) patients suffered from an SAE. The most common events were cardiac (38.4%, n = 105), respiratory (20.8%, n = 77), and neurological (14.1%, n = 77). The majority of SAEs (50.8%, n = 188) occurred in the first 90 days after hip fracture with 35.4% occurring in the first 30 days (n = 131). Body mass index (BMI) between 18.5 and 24.9 compared with BMI between 25 and 29.9 [hazard ratio (HR) 1.32, P = 0.03] and receiving a total hip arthroplasty compared with a bipolar hemiarthroplasty (HR 1.36, P = 0.03) were associated with a higher risk of a medical SAE within 24 months of femoral neck fracture. Age (P = 0.09), use of femoral cement (P = 0.59), and use of canal pressurization (P = 0.37) were not associated with a medical SAE. CONCLUSION: Total hip arthroplasty is associated with more SAEs in the immediate postoperative period, and care should be taken in selecting patients for this treatment compared with a hemiarthroplasty. A higher BMI may be protective in hip fracture patients while age alone does not predict SAEs and neither does the use of femoral cement and/or pressurization. LEVEL OF EVIDENCE: Prognostic Level II. See Instructions for Authors for a complete description of levels of evidence

Enlightened or Delusional?: Differentiating Religious, Spiritual, and Transpersonal Experiences from Psychopathology

Psychological diagnosis faces unique challenges when used to differentiate nonpsychopathological religious/spiritual/transpersonal (R/S/T) experiences from those that might evidence psychopathology, particularly considering the diversity of such experiences and the value-laden assumptions inherent in most diagnostic practices. Theoretical and pragmatic problems related to the diagnostic category, Religious and Spiritual Problem, as contained in the Diagnostic and Statistical Manual of Mental Disorders are discussed. Attention is paid to identifying potential biases and errors in using, or failing to use, this diagnostic category, particularly as related to developing culturally sensitive diagnoses. Specific methods, including psychometric approaches, for evaluating R/S/T experiences that may range from healthy to psychopathological are reviewed and recommendations are presented for improving current diagnostic practices and furthering needed research.Yeshttps://us.sagepub.com/en-us/nam/manuscript-submission-guideline

Outsourcing Governance: States and the Politics of a ‘Global Value Chain World’

Politics, and by extension states, are marginal in debates about the genesis, evolution and functioning of the GVC-based global economy. We contend here that the core complexity of state agency and state power needs to be much more carefully understood in GVC and related debates, as a basis on which the governance of the evolving GVC world can be properly theorised as revolving around the inseparability of economic and political power. We advance a framework for understanding the role of politics and states in the construction and maintenance of a GVC world, using a three-fold typology of facilitative, regulatory and distributive forms of governance, and propose a notion of ‘outsourcing governance’ as an attempt to capture the ways in which states purposefully, through active political agency, have engaged in a process of delegating a variety of governance functions and authority to private actors. Our overarching argument is normative: ‘outsourced governance’ of the form we currently observe is associated with regressive distributional outcomes, and is antithetical to an inclusive and sustainable global economy

Multifunctional metal matrix composites with embedded printed electrical materials fabricated by Ultrasonic Additive Manufacturing

This work proposes a new method for the fabrication of Multifunctional Metal Matrix Composite (MMC) structures featuring embedded printed electrical materials through Ultrasonic Additive Manufacturing (UAM). Printed electrical circuitries combining conductive and insulating materials were directly embedded within the interlaminar region of UAM aluminium matrices to realise previously unachievable multifunctional composites. A specific surface flattening process was developed to eliminate the risk of short circuiting between the metal matrices and printed conductors, and simultaneously reduce the total thickness of the printed circuitry. This acted to improve the integrity of the UAM MMC’s and their resultant mechanical strength. The functionality of embedded printed circuitries was examined via four-point probe measurement. DualBeam Scanning Electron Microscopy (SEM) and Focused Ion Beam (FIB) milling were used to investigate the microstructures of conductive materials to characterize the effect of UAM embedding energy whilst peel testing was used to quantify mechanical strength of MMC structures in combination with optical microscopy. Through this process, fully functioning MMC structures featuring embedded insulating and conductive materials were realised whilst still maintaining high peel resistances of ca. 70 N and linear weld densities of ca. 90%