Pathogen Response Genes Mediate Caenorhabditis elegans Innate Immunity

Innate immunity is crucial in the response and defense against pathogens for invertebrates and vertebrates alike. The soil nematode Caenorhabditis elegans is a useful model to study the eukaryotic innate immune response to microbial pathogenesis. Prior research indicates that the protein receptor FSHR-1 plays an important role in the innate recognition of intestinal infection due to pathogen consumption. Determining what genes are controlled by FSHR-1 may uncover an unknown pathway that could increase not only the comprehension of the C. elegans immune system but also innate immunity generally. To characterize the function of FSHR-1, four candidate pathogen response genes that appear to be regulated by FSHR-1 were evaluated in worms infected with Pseudomonas aeruginosa. Although intestine specific RNA interference of these four genes did not show immunity phenotypes, quantitative PCR suggests that FSHR-1 regulates the basal and/or infection-induced expression of three of the four genes. To explore this FSHR-1-dependent transcriptional induction, fluorescent transgenic reporters were constructed for the three candidate FSHR-1 target genes. The spatial expression of one putative pathogen response gene was characterized in transgenic worms under both control and pathogenic conditions. RNA interference was performed to assess the FSHR-1 dependency of this expression pattern

Determining the Territorial Scope of State Law in Interstate and International Conflicts: Comments on the Draft Restatement (Third) and on the Role of Party Autonomy

Analyzing a conflict of laws requires thinking both about the scope of potentially applicable law and about priority, or choice, among potentially applicable laws. The Restatement (Second) of Conflict of Laws, published in 1971, contains little guidance on how, or in what order, courts are to address these two inquiries. The draft Restatement (Third), in contrast, differentiates clearly the respective roles of the two analytical elements. It characterizes the resolution of a choice-of-law question as a two-step process. First, the scope of the relevant states’ internal laws must be determined, in order to ascertain which states’ laws might be used as a rule of decision. Second, if more than one state’s law might be used as a rule of decision, and those laws conflict, it must be decided which law is given priority. The draft defines “internal law” to include restrictions on the geographic scope of the law. However, there are two questions the draft does not answer clearly. First, is the definition of internal law meant to include only express restrictions on scope? Second, absent explicit indications of legislative intent, how is the scope of a law to be determined? In particular, should courts employ a presumption against the extraterritorial application of state law? This article begins by analyzing the role of the presumption against extraterritoriality in supplying implied restrictions on the scope of law. It considers the role of the presumption in both international and interstate conflicts of laws, and argues that the Restatement (Third) should differentiate clearly between those two contexts. It then turns to the question whether geographic scope restrictions should properly be considered part of a state’s internal law. The paper analyzes that question through the lens of a common problem: a contract dispute involving a transaction or event that falls outside the scope of the law chosen by the parties to govern their agreement. On the basis of that analysis, it concludes that forthcoming sections will need to address the implications of the draft’s categorical treatment of legislative scope

A Review of Ankylosing Spondylitis

Ankylosing spondylitis (AS) is a systemic autoimmune disorder that induces ankylosis of the spine (fusion of the vertebrae at their various joints) and inflammatory arthritis of peripheral joints among other symptoms. Overexpression of cytokines, the presence of genetic mutations not exclusive to the human leucocyte antigen (HLA)-B27 region, and environmental factors all have large roles in the progressive development of AS. Although a definitive pathology continues to be sought after, researchers believe the adaptive immune system in AS patients attacks fibrocartilaginous entheses (supportive connective tissue between bone and attached structures like tendon, ligament, and fascia). AS markedly reduces proper systemic functioning in several areas of human physiology, including the musculoskeletal, cardiovascular, neurological, psychiatric, and reproductive systems in both genders. A diagnosis for this disease requires the presentation of several qualifying symptoms, namely chronic inflammatory back pain, peripheral joint arthritis, enthesitis (inflammation of the enthesis not associated with a joint), uveitis (inflammation of the uvea or inner eye layer), and positive response to non-steroidal anti-inflammatory drugs (NSAIDs), with radiological support through x-ray or magnetic resonance imaging (MRI). Upon an AS diagnosis, patients should engage in healthy lifestyle changes, non-impact exercise, and taking NSAIDs as the first pharmacological treatment. Symptoms unresolved by NSAIDs are then treated with disease modifying antirheumatic drugs (DMARDs) and/or biologic medications like a monoclonal TNFα antibody to prevent further disease progression. Continued research to understand the association between AS and interleukin (IL)-17/IL-23 is needed for development of additional biologic treatments

The Association Between Advanced Maternal Age and Short Interpregnancy Intervals on Preterm Labor

Background: Preterm birth is the leading cause of neonatal and infant mortality and has become a major health concern due to the increasing rates of infant deaths in the United States (WHO, 2017). Studying maternal risk factors for preterm labor provides insight to this obscure condition and can assist in the identification of high risk women, as well as facilitate appropriate pregnancy planning. Purpose: Although research can be found on interpregnancy intervals and maternal age as independent risk factors for premature labor, gaps exist within the relation of these variables. This study was done to investigate whether there is a significant risk association between advanced maternal age (35 years and older) and short interpregnancy intervals on premature labor, that deems transferring out of a low risk birthing center to a more advanced hospitalized setting. Methodology: De-identified data regarding obstetric history, medical history, and pregnancy morbidity was abstracted from women who delivered at Baby + Co., a birthing center in Nashville, Tennessee, between the years of 2015 and 2018. The population set included 1001 women, 5 of which delivered preterm. Means and standard deviations for the two groups were calculated, and two sided t-tests and corresponding p-values were calculated. Result: There was no statistical significance regarding maternal age and preterm transfers (p-value of 0.762). However, there was a positive correlation between short interpregnancy intervals and preterm birth (p-value .007). Discussion: Due to the low risk population included in this study, there is a need for additional research conducted within a higher risk population set to determine the significance and interaction between advanced maternal age and short interpregnancy intervals on preterm labor

Planet Shadows in Protoplanetary Disks. I: Temperature Perturbations

Planets embedded in optically thick passive accretion disks are expected to produce perturbations in the density and temperature structure of the disk. We calculate the magnitudes of these perturbations for a range of planet masses and distances. The model predicts the formation of a shadow at the position of the planet paired with a brightening just beyond the shadow. We improve on previous work on the subject by self-consistently calculating the temperature and density structures under the assumption of hydrostatic equilibrium and taking the full three-dimensional shape of the disk into account rather than assuming a plane-parallel disk. While the excursion in temperatures is less than in previous models, the spatial size of the perturbation is larger. We demonstrate that a self-consistent calculation of the density and temperature structure of the disk has a large effect on the disk model. In addition, the temperature structure in the disk is highly sensitive to the angle of incidence of stellar irradition at the surface, so accurately calculating the shape of the disk surface is crucial for modeling the thermal structure of the disk.Comment: 14 pages, 14 figures. To appear in Ap

Emergent Landscape: Urban Shadow Space, Illuminated

This study defines a new approach to the transformation of unmaintained land within cities, or urban shadow space. Although urban shadow space can offer a place of free expression for the community and spontaneous vegetative growth within a city, it is often dismissed as blighted land by public authority. This study maximizes existing opportunities of these spaces, illuminating a realm of the city that is currently dark to the public eye. A proposed set of guidelines is utilized in the creation of three alternative designs that illustrate the emergent landscape, a sensitively designed, evolving landscape that encourages user interaction with the site. These guidelines and the results of their application are intended to assist design professionals who wish to move beyond the typical “clean and green” strategy currently employed by many municipalities to embrace a site’s existing characteristics

RAGE Signaling in Skeletal Biology

PURPOSE OF REVIEW: The receptor for advanced glycation end products (RAGE) and several of its ligands have been implicated in the onset and progression of pathologies associated with aging, chronic inflammation, and cellular stress. In particular, the role of RAGE and its ligands in bone tissue during both physiological and pathological conditions has been investigated. However, the extent to which RAGE signaling regulates bone homeostasis and disease onset remains unclear. Further, RAGE effects in the different bone cells and whether these effects are cell-type specific is unknown. The objective of the current review is to describe the literature over RAGE signaling in skeletal biology as well as discuss the clinical potential of RAGE as a diagnostic and/or therapeutic target in bone disease. RECENT FINDINGS: The role of RAGE and its ligands during skeletal homeostasis, tissue repair, and disease onset/progression is beginning to be uncovered. For example, detrimental effects of the RAGE ligands, advanced glycation end products (AGEs), have been identified for osteoblast viability/activity, while others have observed that low level AGE exposure stimulates osteoblast autophagy, which subsequently promotes viability and function. Similar findings have been reported with HMGB1, another RAGE ligand, in which high levels of the ligand are associated with osteoblast/osteocyte apoptosis, whereas low level/short-term administration stimulates osteoblast differentiation/bone formation and promotes fracture healing. Additionally, elevated levels of several RAGE ligands (AGEs, HMGB1, S100 proteins) induce osteoblast/osteocyte apoptosis and stimulate cytokine production, which is associated with increased osteoclast differentiation/activity. Conversely, direct RAGE-ligand exposure in osteoclasts may have inhibitory effects. These observations support a conclusion that elevated bone resorption observed in conditions of high circulating ligands and RAGE expression are due to actions on osteoblasts/osteocytes rather than direct actions on osteoclasts, although additional work is required to substantiate the observations. Recent studies have demonstrated that RAGE and its ligands play an important physiological role in the regulation of skeletal development, homeostasis, and repair/regeneration. Conversely, elevated levels of RAGE and its ligands are clearly related with various diseases associated with increased bone loss and fragility. However, despite the recent advancements in the field, many questions regarding RAGE and its ligands in skeletal biology remain unanswered