Alanyl-glutamine has no effect on epidural fibrosis in a post-laminectomy rat model

Epidural fibrosis following spinal surgery is common, and subsequent reoperations are more technically challenging with higher complication rates. A safe and effective therapeutic solution to this difficult clinical problem has yet to be realized. Previous research has demonstrated the effectiveness of alanyl-glutamine in reduction of peritoneal adhesions in a rat abdominal sepsis model. I hypothesized that alanyl-glutamine may be similarly efficacious in minimizing epidural fibrosis in a rat laminectomy model. Rats were randomized into three groups: no surgery, laminectomy/normal saline and laminectomy/alanyl-glutamine (1g/kg). The surgical groups underwent a lumbar laminectomy with instillation of either normal saline or alanyl-glutamine into the peridural space. Thirty days after surgery, the rats were euthanized and the spinal columns prepared for histological evaluation. A blinded veterinary pathologist and a less experienced student independently graded the extent and maturity of epidural fibrosis. The laminectomy model was an effective model for epidural fibrosis formation. Rats that underwent laminectomy demonstrated significant fibrosis compared to control animals (p<0.001). However, there was no significant difference in histological grade of fibrosis between normal saline and alanyl-glutamine treatment groups (p=0.83). Based on this study, alanyl-glutamine does not appear to have an effect in reducing epidural fibrosis at a histological level. It is possible that alanyl-glutamine may have an effect that is not detectable using this model, in which case further studies with a more sensitive model may be indicated. Resources may be better used elucidating the mechanism by which glutamine acts to reduce adhesions in the peritoneal model and further studies exploiting those mechanisms can be designed

Beviskrav og bevistema ved ilegging av tilleggsskatt

Hovudspørsmålet i oppgåva er kva som er beviskravet og bevistemaet ved ilegging av tilleggsskatt. Eg skal drøfta utvalde spørsmål knytt til problemstillinga, som utspelar ei rolle i det praktiske rettsliv.MasteroppgåveJUS399MAJUR-2MAJU

Autonomy of Nations and Indigenous Peoples and the Environmental Release of Genetically Engineered Animals with Gene Drives

This article contends that the environmental release of genetically engineered (GE) animals with heritable traits that are patented will present a challenge to the efforts of nations and indigenous peoples to engage in self‐determination. The environmental release of such animals has been proposed on the grounds that they could function as public health tools or as solutions to the problem of agricultural insect pests. This article brings into focus two political‐economic‐legal problems that would arise with the environmental release of such organisms. To address those challenges, it is proposed that nations considering the environmental release of GE animals must take into account the underlying circumstances and policy failures that motivate arguments for the use of the modified animals. Moreover, countries must recognize that the UN International Covenant on Civil and Political Rights and the UN International Covenant on Economic, Social and Cultural Rights place on them an obligation to ensure that GE animals with patented heritable traits are not released without the substantive consent of the nations or indigenous peoples that could be affected

A new approach to evaluate forest structure restoration needs across Oregon and Washington, USA

Widespread habitat degradation and uncharacteristic fire, insect, and disease outbreaks in forests across the western United States have led to highly publicized calls to increase the pace and scale of forest restoration. Despite these calls, we frequently lack a comprehensive understanding of forest restoration needs. In this study we demonstrate a new approach for evaluating where, how much, and what types of restoration are needed to move present day landscape scale forest structure towards a Natural Range of Variability (NRV) across eastern Washington, eastern Oregon, and southwestern Oregon. Our approach builds on the conceptual framework of the LANDFIRE and Fire Regime Condition Class programs. Washington–Oregon specific datasets are used to assess the need for changes to current forest structure resulting from disturbance and/or succession at watershed and regional scales. Across our analysis region we found that changes in current structure would be needed on an estimated 4.7 million+ ha (40% of all coniferous forests) in order to restore forest structure approximating NRV at the landscape scale. Both the overall level and the type of restoration need varied greatly between forested biophysical settings. Regional restoration needs were dominated by the estimated 3.8+ million ha in need of thinning and/or low severity fire in forests that were historically maintained by frequent low or mixed severity fire (historical Fire Regime Group I and III biophysical settings). However, disturbance alone cannot restore NRV forest structure. We found that time to transition into later development structural classes through successional processes was required on approximately 3.2 million ha (over 25% of all coniferous forests). On an estimated 2.3 million ha we identified that disturbance followed by succession was required to restore NRV forest structure. The results of this study are intended to facilitate the ability of local land managers to incorporate regional scale, multi-ownership context into local forest management and restoration. Meeting the region-wide restoration needs identified in this study will require a substantial increase in the pace and scale of restoration treatments and coordination amongst governments, agencies, and landowners.Keywords: Landfire, Fire Regime Condition Class, Gradient nearest neighbor, Natural range of variation, Ecological restoration, Pacific Northwes

The Pyrimidine Nucleotide Biosynthetic Pathway Modulates Production of Biofilm Determinants in Escherichia coli

Bacteria are often found in multicellular communities known as biofilms, which constitute a resistance form against environmental stresses. Extracellular adhesion and cell aggregation factors, responsible for bacterial biofilm formation and maintenance, are tightly regulated in response to physiological and environmental cues. We show that, in Escherichia coli, inactivation of genes belonging to the de novo uridine monophosphate (UMP) biosynthetic pathway impairs production of curli fibers and cellulose, important components of the bacterial biofilm matrix, by inhibiting transcription of the csgDEFG operon, thus preventing production of the biofilm master regulator CsgD protein. Supplementing growth media with exogenous uracil, which can be converted to UMP through the pyrimidine nucleotide salvage pathway, restores csgDEFG transcription and curli production. In addition, however, exogenous uracil triggers cellulose production, particularly in strains defective in either carB or pyrB genes, which encode enzymes catalyzing the first steps of de novo UMP biosynthesis. Our results indicate the existence of tight and complex links between pyrimidine metabolism and curli/cellulose production: transcription of the csgDEFG operon responds to pyrimidine nucleotide availability, while cellulose production is triggered by exogenous uracil in the absence of active de novo UMP biosynthesis. We speculate that perturbations in the UMP biosynthetic pathways allow the bacterial cell to sense signals such as starvation, nucleic acids degradation, and availability of exogenous pyrimidines, and to adapt the production of the extracellular matrix to the changing environmental conditions

A Communal Bacterial Adhesin Anchors Biofilm and Bystander Cells to Surfaces

While the exopolysaccharide component of the biofilm matrix has been intensively studied, much less is known about matrix-associated proteins. To better understand the role of these proteins, we undertook a proteomic analysis of the V. cholerae biofilm matrix. Here we show that the two matrix-associated proteins, Bap1 and RbmA, perform distinct roles in the biofilm matrix. RbmA strengthens intercellular attachments. In contrast, Bap1 is concentrated on surfaces where it serves to anchor the biofilm and recruit cells not yet committed to the sessile lifestyle. This is the first example of a biofilm-derived, communally synthesized conditioning film that stabilizes the association of multilayer biofilms with a surface and facilitates recruitment of planktonic bystanders to the substratum. These studies define a novel paradigm for spatial and functional differentiation of proteins in the biofilm matrix and provide evidence for bacterial cooperation in maintenance and expansion of the multilayer biofilm

Reduced fire severity offers near-term buffer to climate-driven declines in conifer resilience across the western United States

Increasing fire severity and warmer, drier postfire conditions are making forests in the western United States (West) vulnerable to ecological transformation. Yet, the relative importance of and interactions between these drivers of forest change remain unresolved, particularly over upcoming decades. Here, we assess how the interactive impacts of changing climate and wildfire activity influenced conifer regeneration after 334 wildfires, using a dataset of postfire conifer regeneration from 10,230 field plots. Our findings highlight declining regeneration capacity across the West over the past four decades for the eight dominant conifer species studied. Postfire regeneration is sensitive to high-severity fire, which limits seed availability, and postfire climate, which influences seedling establishment. In the near-term, projected differences in recruitment probability between low- and high-severity fire scenarios were larger than projected climate change impacts for most species, suggesting that reductions in fire severity, and resultant impacts on seed availability, could partially offset expected climate-driven declines in postfire regeneration. Across 40 to 42% of the study area, we project postfire conifer regeneration to be likely following low-severity but not high-severity fire under future climate scenarios (2031 to 2050). However, increasingly warm, dry climate conditions are projected to eventually outweigh the influence of fire severity and seed availability. The percent of the study area considered unlikely to experience conifer regeneration, regardless of fire severity, increased from 5% in 1981 to 2000 to 26 to 31% by mid-century, highlighting a limited time window over which management actions that reduce fire severity may effectively support postfire conifer regeneration. © 2023 the Author(s)