Nonsupersymmetric multibrane solutions

Gravity coupled to an arbitrary number of antisymmetric tensors and scalar fields in arbitrary space-time dimensions is studied in a context of general, static, spherically symmetric solutions with many orthogonally intersecting branes. Neither supersymmetry nor harmonic gauge is assumed. It is shown that the system reduces to a Toda-like system after an adequate redefinition of transverse radial coordinate $r$. Duality $r \to 1/r$ in the set of solutions is observed

A Leptin-regulated Circuit Controls Glucose Mobilization During Noxious Stimuli

Adipocytes secrete the hormone leptin to signal the sufficiency of energy stores. Reductions in circulating leptin concentrations reflect a negative energy balance, which augments sympathetic nervous system (SNS) activation in response to metabolically demanding emergencies. This process ensures adequate glucose mobilization despite low energy stores. We report that leptin receptor–expressing neurons (LepRb neurons) in the periaqueductal gray (PAG), the largest population of LepRb neurons in the brain stem, mediate this process. Application of noxious stimuli, which often signal the need to mobilize glucose to support an appropriate response, activated PAG LepRb neurons, which project to and activate parabrachial nucleus (PBN) neurons that control SNS activation and glucose mobilization. Furthermore, activating PAG LepRb neurons increased SNS activity and blood glucose concentrations, while ablating LepRb in PAG neurons augmented glucose mobilization in response to noxious stimuli. Thus, decreased leptin action on PAG LepRb neurons augments the autonomic response to noxious stimuli, ensuring sufficient glucose mobilization during periods of acute demand in the face of diminished energy stores

p21 promotes oncolytic adenoviral activity in ovarian cancer and is a potential biomarker

The oncolytic adenovirus dl922-947 replicates selectively within and lyses cells with a dysregulated Rb pathway, a finding seen in &gt; 90% human cancers. dl922-947 is more potent than wild type adenovirus and the E1B-deletion mutant dl1520 (Onyx-015). We wished to determine which host cell factors influence cytotoxicity. SV40 large T-transformed MRC5-VA cells are 3-logs more sensitive to dl922-947 than isogenic parental MRC5 cells, confirming that an abnormal G1/S checkpoint increases viral efficacy. The sensitivity of ovarian cancer cells to dl922-947 varied widely: IC50 values ranged from 51 (SKOV3ip1) to 0.03 pfu/cell (TOV21G). Cells sensitive to dl922-947 had higher S phase populations and supported earlier E1A expression. Cytotoxicity correlated poorly with both infectivity and replication, but well with expression of p21 by microarray and western blot analyses. Matched p21+/+ and -/- Hct116 cells confirmed that p21 influences dl922-947 activity in vitro and in vivo. siRNA-mediated p21 knockdown in sensitive TOV21G cells decreases E1A expression and viral cytotoxicity, whilst expression of p21 in resistant A2780CP cells increases virus activity in vitro and in intraperitoneal xenografts. These results highlight that host cell factors beyond simple infectivity can influence the efficacy of oncolytic adenoviruses. p21 expression may be an important biomarker of response in clinical trials.</p

Evaluation of Single-Chip, Real-Time Tomographic Data Processing on FPGA - SoC Devices

A novel approach to tomographic data processing has been developed and evaluated using the Jagiellonian PET (J-PET) scanner as an example. We propose a system in which there is no need for powerful, local to the scanner processing facility, capable to reconstruct images on the fly. Instead we introduce a Field Programmable Gate Array (FPGA) System-on-Chip (SoC) platform connected directly to data streams coming from the scanner, which can perform event building, filtering, coincidence search and Region-Of-Response (ROR) reconstruction by the programmable logic and visualization by the integrated processors. The platform significantly reduces data volume converting raw data to a list-mode representation, while generating visualization on the fly.Comment: IEEE Transactions on Medical Imaging, 17 May 201

ER stress transcription factor Xbp1 suppresses intestinal tumorigenesis and directs intestinal stem cells

Unresolved endoplasmic reticulum (ER) stress in the epithelium can provoke intestinal inflammation. Hypomorphic variants of ER stress response mediators, such as X-box–binding protein 1 (XBP1), confer genetic risk for inflammatory bowel disease. We report here that hypomorphic Xbp1 function instructs a multilayered regenerative response in the intestinal epithelium. This is characterized by intestinal stem cell (ISC) expansion as shown by an inositol-requiring enzyme 1α (Ire1α)–mediated increase in Lgr5+ and Olfm4+ ISCs and a Stat3-dependent increase in the proliferative output of transit-amplifying cells. These consequences of hypomorphic Xbp1 function are associated with an increased propensity to develop colitis-associated and spontaneous adenomatous polyposis coli (APC)–related tumors of the intestinal epithelium, which in the latter case is shown to be dependent on Ire1α. This study reveals an unexpected role for Xbp1 in suppressing tumor formation through restraint of a pathway that involves an Ire1α- and Stat3-mediated regenerative response of the epithelium as a consequence of ER stress. As such, Xbp1 in the intestinal epithelium not only regulates local inflammation but at the same time also determines the propensity of the epithelium to develop tumors

Identification of Degraded Land in the Canary Islands; Tests and Reviews

Degraded Land is an area that either by natural causes (fires, floods, storms or volcanic eruptions) or more by direct or indirect causes of human action, has been altered or modified from its natural state. Restoration is an activity that initiates or accelerates the recovery of an ecosystem. It can be defined as the set of actions taken in order to reverse or reduce the damage caused in the territory. In the case of the Canary Islands there is a high possibility for the territory to suffer processes that degrade the environment, given that the islands are very fragile ecosystems. Added to this they are territories isolated from the continent, which complicates the process of restoring them. In this paper, the different types of common degraded areas in the Canary Islands are identified, as well as the proposed solutions for remediation, such as afforestation of agricultural land or landfill closure and restoration

Aspirin activates resolution pathways to reprogram T cell and macrophage responses in colitis-associated colorectal cancer.

[EN]Inflammation is linked with carcinogenesis in many types of cancer including colorectal cancer (CRC). Aspirin is recommended for the prevention of CRC, although the mechanism(s) mediating its immunomodulatory actions remain incompletely understood. Here, we demonstrate that aspirin increased concentrations of the immune-regulatory aspirin-triggered specialized proresolving mediators (AT-SPMs), including AT-lipoxin A4 and AT-resolvin D1, in colonic tissues during inflammation-associated CRC (I-CRC). Aspirin also down-regulated the expression of the checkpoint protein programmed cell death protein-1 in macrophages and CD8+ T cells from the colonic mucosa. Inhibition of AT-SPM biosynthesis or knockout of the AT-SPM receptor Alx/Fpr2 reversed the immunomodulatory actions of aspirin on macrophages and CD8+ T cells and abrogated its protective effects during I-CRC. Furthermore, treatment of mice with AT-SPM recapitulated the immune-directed actions of aspirin during I-CRC. Together, these findings elucidate a central role for AT-SPM in mediating the immune-directed actions of aspirin in regulating I-CRC progression

Intestinal epithelial cell endoplasmic reticulum stress promotes MULT1 up-regulation and NKG2D-mediated inflammation

Endoplasmic reticulum (ER) stress is commonly observed in intestinal epithelial cells (IECs) and can, if excessive, cause spontaneous intestinal inflammation as shown by mice with IEC-specific deletion of X-box-binding protein 1 (Xbp1), an unfolded protein response-related transcription factor. In this study, Xbp1 deletion in the epithelium (Xbp1ΔIEC ) is shown to cause increased expression of natural killer group 2 member D (NKG2D) ligand (NKG2DL) mouse UL16-binding protein (ULBP)-like transcript 1 and its human orthologue cytomegalovirus ULBP via ER stress-related transcription factor C/EBP homology protein. Increased NKG2DL expression on mouse IECs is associated with increased numbers of intraepithelial NKG2D-expressing group 1 innate lymphoid cells (ILCs; NK cells or ILC1). Blockade of NKG2D suppresses cytolysis against ER-stressed epithelial cells in vitro and spontaneous enteritis in vivo. Pharmacological depletion of NK1.1+ cells also significantly improved enteritis, whereas enteritis was not ameliorated in Recombinase activating gene 1-/-;Xbp1ΔIEC mice. These experiments reveal innate immune sensing of ER stress in IECs as an important mechanism of intestinal inflammation

Osseous erosion by herniated nucleus pulposus mimicking intraspinal tumor: a case report

Erosion of spinal osseous structure, so-called scalloping, has been rarely reported associated with herniated nucleus pulposus (HNP). We report a rare case of HNP causing erosion of the spinal osseous structure (including lamina). The patient was an 81-year-old woman with 3-year history of low-back pain and left leg radiating pain. Muscle weakness of the left leg was also apparent. Computed tomography following myelography showed severe compression of the dural sac at the level of L3–L4; furthermore, erosion of the lamina, pedicle, and vertebral body was noted, indicating that the space-occupying mass was most probably a tumorous lesion. The mass also showed calcification inside. During the surgery, the mass was confirmed to be an HNP with calcification. Following resection, the pain disappeared. Surgeons should be aware of the possibility of scalloping of the vertebrae caused by HNP mimicking a tumorous lesion

The design, evaluation, and reporting on non- pharmacological, cognition- oriented treatments for older adults: Results of a survey of experts

IntroductionCognitive decline and dementia significantly affect independence and quality of life in older adults; therefore, it is critical to identify effective cognition- oriented treatments (COTs; eg, cognitive training, rehabilitation) that can help maintain or enhance cognitive functioning in older adults, as well as reduce dementia risk or alleviate symptoms associated with pathological processes.MethodsThe Cognitive Intervention Design Evaluation and Reporting (CIDER), a working group from the Non- Pharmacological Interventions Professional Interest Area (NPI- PIA) of the Alzheimer’s Association conducted as survey in 2017 with experts in COTs worldwide. The survey’s aims were three- fold: (1) determine the common attitudes, beliefs, and practices of experts involved in the COTs research targeting older people; (2) identify areas of relative agreement and disagreement among experts in the field; and (3) offer a critical review of the literature, including recommendations for future research.ResultsThe survey identified several areas of agreements among experts on critical features of COTs, and on study design and outcome measures. Nevertheless, there were some areas with relative disagreement. Critically, expert opinions were not always supported by scientific evidence, suggesting that methodologic improvements are needed regarding design, implementation, and reporting of COTs. There was a clear consensus that COTs provide benefits and should be offered to cognitively unimpaired older adults, mild cognitive impairment (MCI), and mild dementia, but opinions differed for moderate and severe dementia. In addition, there is no consensus on the potential role of COTs in dementia prevention, indicating that future research should prioritize this aspect.DiscussionEvidence of COTs in older adults is encouraging, but additional evidence is needed to enhance dementia prevention. Consensus building and guidelines in the field are critical to improve and accelerate the development of high- quality evidence for COTs in cognitively unimpaired older adults, and those with MCI and dementia.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/155935/1/trc212024_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/155935/2/trc212024.pd