bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficacy and Pharmacology of the NLRP3 Inflammasome Inhibitor CP-456,773 (CRID3) in Murine Models of Dermal and Pulmonary Inflammation
Authors: Primiano Michael J. , Lefker Bruce A. , Bowman Michael R. , Bree Andrea G. , Hubeau Cedric , Bonin Paul D. , Mangan Matthew , Dower Ken , Monks Brian G. , Cushing Leah , Wang Stephen , Guzova Julia , Jiao Aiping , Lin Lih-Ling , Latz Eicke , Hepworth David , Hall J. Perry 
Published: August 2016

Abstract
A critical component of innate immune response to infection and tissue damage is the NACHT, LRR, and PYD domains–containing protein 3 (NLRP3) inflammasome, and this pathway and its activation products have been implicated in the pathophysiology of a variety of diseases. NLRP3 inflammasome activation leads to the cleavage of pro–IL-1β and pro–IL-18, as well as the subsequent release of biologically active IL-1β, IL-18, and other soluble mediators of inflammation. In this study, we further define the pharmacology of the previously reported NLRP3 inflammasome–selective, IL-1β processing inhibitor CP-456,773 (also known as MCC950), and we demonstrate its efficacy in two in vivo models of inflammation. Specifically, we show that in human and mouse innate immune cells CP-456,773 is an inhibitor of the cellular release of IL-1β, IL-1α, and IL-18, that CP-456,773 prevents inflammasome activation induced by disease-relevant soluble and crystalline NLRP3 stimuli, and that CP-456,773 inhibits R848- and imiquimod-induced IL-1β release. In mice, CP-456,773 demonstrates potent inhibition of the release of proinflammatory cytokines following acute i.p. challenge with LPS plus ATP in a manner that is proportional to the free/unbound concentrations of the drug, thereby establishing an in vivo pharmacokinetic/pharmacodynamic model for CP-456,773. Furthermore, CP-456,773 reduces ear swelling in an imiquimod cream–induced mouse model of skin inflammation, and it reduces airway inflammation in mice following acute challenge with house dust mite extract. These data implicate the NLRP3 inflammasome in the pathogenesis of dermal and airway inflammation, and they highlight the utility of CP-456,773 for interrogating the contribution of the NLRP3 inflammasome and its outputs in preclinical models of inflammation and disease.
New Murine Model of Early Onset Autoimmune Thyroid Disease/Hypothyroidism and Autoimmune Exocrinopathy of the Salivary Gland
Authors: Kayes Timothy Daniel , Weisman Gary A. , Camden Jean M. , Woods Lucas T. , Bredehoeft Cole , Downey Edward F. , Cole James , Braley-Mullen Helen 
Published: August 2016

Abstract
Sixty to seventy percent of IFN-γ−/− NOD.H-2h4 mice given sodium iodide (NaI)–supplemented water develop a slow onset autoimmune thyroid disease, characterized by thyrocyte epithelial cell (TEC) hyperplasia and proliferation (H/P). TEC H/P develops much earlier in CD28−/− mice and nearly 100% (both sexes) have severe TEC H/P at 4 mo of age. Without NaI supplementation, 50% of 5- to 6-mo-old CD28−/−IFN-γ−/− mice develop severe TEC H/P, and 2–3 wk of NaI is sufficient for optimal development of severe TEC H/P. Mice with severe TEC H/P are hypothyroid, and normalization of serum thyroxine levels does not reduce TEC H/P. Activated CD4+ T cells are sufficient to transfer TEC H/P to SCID recipients. Thyroids of mice with TEC H/P have infiltrating T cells and expanded numbers of proliferating thyrocytes that highly express CD40. CD40 facilitates, but is not required for, development of severe TEC H/P, as CD40−/−IFN-γ−/−CD28−/− mice develop severe TEC H/P. Accelerated development of TEC H/P in IFN-γ−/−CD28−/− mice is a result of reduced regulatory T cell (Treg) numbers, as CD28−/− mice have significantly fewer Tregs, and transfer of CD28+ Tregs inhibits TEC H/P. Essentially all female IFN-γ−/−CD28−/− NOD.H-2h4 mice have substantial lymphocytic infiltration of salivary glands and reduced salivary flow by 6 mo of age, thereby providing an excellent new model of autoimmune exocrinopathy of the salivary gland. This is one of very few models where autoimmune thyroid disease and hypothyroidism develop in most mice by 4 mo of age. This model will be useful for studying the effects of hypothyroidism on multiple organ systems.
Local Microenvironment Controls the Compartmentalization of NK Cell Responses during Systemic Inflammation in Mice
Authors: Rasid Orhan , Ciulean Ioana Sonya , Fitting Catherine , Doyen Noelle , Cavaillon Jean-Marc 
Published: August 2016

Abstract
Systemic inflammatory response syndrome is a whole-body reaction to a triggering insult that often results in life-threatening illness. Contributing to the development of this inflammatory cascade are numerous cellular partners, among which NK cells were shown to play a key role. Accumulating evidence points to organ-specific properties of systemic inflammation and NK cells. However, little is known about compartment-specific activation of NK cells during systemic inflammatory response syndrome or the relative contribution of NK cell–intrinsic properties and microenvironmental cues. In this study, we undertook a sequential characterization of NK responses in the spleen, lungs, bone marrow, peritoneum, and blood using a mouse model of endotoxemia. We report that, despite similar systemic dynamics of NK cell responses, expression of activation markers (CD69 and CD25) and effector molecules (IFN-γ, granzyme B, and IL-10) display organ-specific thresholds of maximum activation. Using adoptive transfers of spleen and lung NK cells, we found that these cells have the capacity to quickly adapt to a new environment and adjust their response levels to that of resident NK cells. This functional adaptation occurs without significant alterations in phenotype and independently of subpopulation-specific trafficking. Thus, using a dynamic in vivo–transfer system, to our knowledge our study is the first to report the compartmentalization of NK cells responses during systemic inflammation and to show that NK cell–intrinsic properties and microenvironmental cues are involved in this process, in a sequential manner.
NFIL3 Expression Distinguishes Tissue-Resident NK Cells and Conventional NK-like Cells in the Mouse Submandibular Glands
Authors: Erick Timothy K. , Anderson Courtney K. , Reilly Emma C. , Wands Jack R. , Brossay Laurent 
Published: August 2016

Abstract
The submandibular salivary gland (SMG), a major site of persistent infection for many viruses, contains a large NK cell population. Using NFIL3-deficient mice, PLZF reporter/fate mapping mice, and mixed bone marrow chimeras, we identified two distinct populations of NK cells in the SMG. Although phenotypically unique, the main population relies on NFIL3, but not PLZF, for development and, therefore, is developmentally similar to the conventional NK cell subset. In contrast, we found that approximately one quarter of the SMG NK cells develop independently of NFIL3. Interestingly, NFIL3-independent SMG tissue-resident NK (trNK) cells are developmentally distinct from liver trNK cells. We also demonstrated that the SMG NK cell hyporesponsive phenotype during murine CMV infection is tissue specific and not cell intrinsic. In contrast, NFIL3-independent SMG trNK cells are intrinsically hyporesponsive. Altogether, our data show that the SMG tissue environment shapes a unique repertoire of NK-like cells with distinct phenotypes.
A theology of sin related to poverty
Authors: Kakwata Frederick 
Published: August 2016

This article is a literature study and seeks to explore the correlation between sin and poverty. It is an important subject since it helps researchers and policy makers to understand what lies at the root of the persisting cycle of poverty within contemporary society globally, and particularly in Africa. The point of departure for this investigation is based on Myers’ (2007:88) assumption: ‘without a strong theology of sin, comprehensive explanations of poverty are hard to come by’. It is argued that sin entails the violation of God’s standard of loving Him and caring for others, which applies at a personal as well as societal level. It will be demonstrated that poverty as a situation of dire needs or a lack of means for survival is caused mainly by oppression and economic exploitation. These conditions express dysfunctional relationships, which portrays the lack of love. The virtue of love is therefore a key factor that provides correctives for the relationship between sin and poverty.
Progression and Issues in the Mesoamerican Geospatial Revolution
Authors: Chase Arlen F. , Reese-Taylor Kathryn , Fernandez-Diaz Juan C. , Chase Diane Z. 
Published: August 2016

AbstractThe use of airborne mapping lidar (Light Detection and Ranging), a.k.a airborne laser scanning (ALS), has had a major impact on archaeological research being carried out in Mesoamerica. Since being introduced in 2009, mapping lidar has revolutionized the spatial parameters of Mesoamerican, and especially Maya, archaeology by permitting the recovery of a complete landscape and settlement pattern for further analysis. However, like any new technology, there are learning curves to be overcome, resulting in a feedback relationship between the on-the-ground archaeologists, the virtually grounded computer analysts, and the instrument designers. Archaeologists have been able to identify problems and issues with data production and visualization for the determination of archaeological remains caused by vegetation, special terrain conditions, and modern disturbance. The identification of these concerns helps the technician to develop new techniques, especially when working in conjunction with the field researcher. As seen through the papers in this volume, this symbiotic relationship promises to yield both new breakthroughs in landscape and settlement analysis for Mesoamerican archaeology and enhanced analytic and visualization techniques for lidar with the potential for applicability in other contexts. In many regards, the development of lidar has parallels to the development of radiocarbon dating as a revolutionary technology.
Integrating Quantitative Lidar Analysis and Settlement Survey in the Belize River Valley
Authors: Ebert Claire E. , Hoggarth Julie A. , Awe Jaime J. 
Published: August 2016

AbstractAccurate and high-resolution airborne light detection and ranging (lidar) data have become increasingly important for the discovery and visualization of complete archaeological settlement systems in the Maya Lowlands. We present the results of systematic quantitative analysis of lidar data and ground verification for the major centers of Cahal Pech, Baking Pot, and Lower Dover in the Belize Valley. The Belize Valley is characterized by high density populations living in growing modern towns and villages, and by large-scale agricultural production. This urban environment presents a challenge to reconnaissance efforts since modern construction and agricultural activities have destroyed ancient ruins and created new vegetation patterns. Lidar data was analyzed within a GIS using the Topographic Position Index (TPI) to identify the location of possible archaeological remains. Small-scale, site-level TPI analysis helped identify more detailed archaeological features including small house mounds, terraces, and ditches. Results indicate that lidar data recorded for areas with dense vegetation (e.g., low brush and secondary regrowth) may be less reliable for identification of archaeological remains. The quantitative and qualitative differences between spatial analyses and pedestrian survey results among land cover types indicate that traditional settlement pattern study methods, including pedestrian survey, remain vital to ground-truthing all types of spatial data.
Locating and Dating Sites Using Lidar Survey in a Mosaic Landscape in Western Belize
Authors: Yaeger Jason , Brown M. Kathryn , Cap Bernadette 
Published: August 2016

AbstractWe use the results of a high-resolution lidar survey to assess the advantages and limitations of archaeological applications of lidar data and address some of its methodological challenges. Our data come from the Mopan and Macal River valleys in western Belize, a region that includes several ancient Maya political centers and their hinterlands. Visual inspection of the lidar data has revealed many new sites and new features at previously mapped sites, and these findings significantly enhance our understanding of the valley's cultural history and political dynamics. By comparing data from prior systematic pedestrian surveys, visual and TPI analysis of the lidar data, and analysis of other remotely sensed data, we assess the limits of mound visibility in the lidar data and examine how vegetation and topographic factors impact those limits. We also present slope analysis as a useful tool for predicting whether mounds were constructed in the Preclassic period (1000 B.C.–A.D. 250) or the Classic period (A.D. 250–900).
Using Lidar and GIS to Investigate Water and Soil Management in the Agricultural Terracing at Caracol, Belize
Authors: Chase Adrian S.Z. , Weishampel John 
Published: August 2016

AbstractIn April 2009, a lidar survey flown by the National Center for Airborne Laser Mapping recorded 200 square kilometers of terrain that comprised the Classic Period Maya city of Caracol, Belize. The data revealed a highly manipulated landscape of dense settlement, agricultural terraces, and residential reservoirs. Literature on Maya agriculture has discussed the benefits of terraces in controlling soil erosion, retaining water, and managing the gravitational flow of water; however, until now these benefits have not been quantified or demonstrated on the ground at scale. This research utilizes these lidar data and data derivatives in order to test the degree to which the ancient Maya manipulated their environment and were able to support large-scale populations through their landscape management practices. As such, the research provides evidence supporting the significance of agricultural terraces and their impact on limiting soil erosion, increasing water retention, and permitting flow control over rainfall runoff. This research also highlights the conscious effort by the ancient Maya to manage the hydrology of their terraced landscape.
Understanding Ancient Maya Agricultural Terrace Systems through Lidar and Hydrological Mapping
Authors: Macrae Scott , Iannone Gyles 
Published: August 2016

AbstractLidar has been revolutionary to the understanding of ancient Maya anthropogenic landscapes. This is no more apparent than in western Belize, where the scale and resolution of these images have identified vast networks of agricultural terrace systems, revealing their true extent and density. This paper moves beyond the initial identification of terrace distribution to use lidar imagery in combination with digital elevation models (DEM) and hydrological mapping programs (Arc Hydro) to explore the drainage catchments associated with agricultural terraces at the ancient Maya site Waybil, a minor center within the Minanha polity in the North Vaca Plateau. We specifically address how the builders of these relic agricultural features worked with the natural topography to manipulate and create more effective catchments and drainage routes. Results from hydrological modeling describe how terraces created smaller drainage catchments by increasing lower levels of flow accumulation and redirecting routes laterally across the topography. Over a decade of research within this sub-region provides the necessary survey, excavations, and chronological datasets to accurately assess the efficacy of the combined methods for relic terrace drainage analysis.
Lidar-Based Analyses of Anthropogenic Landscape Alterations as a Component of the Built Environment
Authors: Prufer Keith , Thompson Amy E. 
Published: August 2016

AbstractLidar has shown considerable utility for answering specific questions regarding anthropogenic landscape alteration in archaeological contexts. We document the extent and timing of these alterations in the construction of the public and political core architectural groups at Uxbenká, Belize, using combined data from Lidar and archaeological excavations. We detail how Lidar methods combined with archaeological excavations enhance the precision of our measurements of the broad range of impacts on the landscape from investment in the built environment. We conclude that the large social investment in landscape alteration to accommodate public architecture occurred early in the polity's history (prior to A.D. 400) and that later developments, including architectural reconfigurations, did not expand greatly on these initial investments.
Inherited Basaloid Neoplasms Associated With SUFU Pathogenic Variants
Authors: Abbott James J. , Jiang Angela J. , Godse Rama , Ahmed Sarah , Senft Stephen C. , Wilson Melissa A. , Cohen Justine V. , Mitchell Tara C. , Ogunleye Temitayo A. , Higgins H. William , Shin Thuzar M. , Miller Christopher J. , Roth Jacquelyn J. , Priore Salvatore F. , Castelo-Soccio Leslie , Elenitsas Rosalie , Seykora John T. , Nathanson Katherine L. , Chu Emily Y. 
Published: September 2024

ImportanceGermline SUFU pathogenic variants (PVs) have previously been associated with basal cell nevus syndrome (BCNS) and multiple infundibulocystic basal cell carcinoma syndrome; however, a broader spectrum of cutaneous findings in patients with SUFU PVs has not been well delineated.ObjectiveTo define the clinical and histopathologic spectrum of cutaneous findings in patients with germline SUFU PVs.Design, Setting, and ParticipantsThis case series was conducted in multiple US academic dermatology, medical genetics, and medical oncology clinics between July 2014 and July 2022. The study included patients with confirmed germline SUFU PVs who were evaluated by a dermatologist. The analysis took place from March to September 2023.Main Outcomes and MeasuresHistopathologic evaluation of skin biopsies with or without immunohistochemical staining, and targeted next-generation sequencing (NGS) on tumor specimens.ResultsAll 5 patients were women. The mean (range) age at presentation was 50.2 (31-68) years, with skin manifestations initially appearing in the fourth to sixth decades of life. None had keratocystic odontogenic tumors. A total of 29 skin pathology specimens from the 5 patients were reviewed; of these, 3 (10.3%) were diagnosed as basaloid follicular hamartomas (BFHs), 10 (34.5%) classified as infundibulocystic basal cell carcinomas (iBCCs), 6 (20.7%) classified as nodular basal cell carcinomas (nBCCs), and 1 (3.4%) as infiltrative basal cell carcinoma (BCC). Targeted NGS studies on tumor specimens suggest that an increased number of UV-signature variants is associated with basal cell carcinomas compared with more indolent basaloid follicular hamartomas.Conclusions and RelevancePatients with germline SUFU PVs may present with multiple indolent basaloid neoplasms in addition to conventional basal cell carcinomas, typically appearing in the fourth to sixth decades of life. Although there are overlapping clinical manifestations, these findings help to differentiate the clinical syndrome associated with SUFU PVs from PTCH1 BCNS. Awareness of the clinicopathologic spectrum of SUFU-associated basaloid neoplasms is important for dermatologists and dermatopathologists because many (although not all) of these lesions are indolent and do not require aggressive surgical treatment. Importantly, because SUFU lies downstream of the protein smoothened, vismodegib and other smoothened inhibitors are unlikely to be effective therapies in this subset of patients.
Impact of paramagnetic rim lesions on disability and race in multiple sclerosis: mediation analysis
Authors: Michaelson Nara M. , Rúa Sandra H. , Kaunzner Ulrike W. , Marcille Melanie , Pliska‐Bloch Iliana , Markowitz Kimberly , Nguyen Thanh D. , Gauthier Susan A. 
Published: September 2024

AbstractObjectiveBlack American (BA) multiple sclerosis (MS) patients experience greater disability compared to White American (WA) patients. Here, we investigated the role of paramagnetic rim lesions (PRLs), a subset of chronic active lesions, on race‐related disability in MS.MethodsWe conducted a retrospective observational study comparing BA and WA MS patients. PRLs were identified through Quantitative Susceptibility Mapping (QSM) MRI. A causal mediation analysis explored the impact of PRLs on the relationship between race and disability, as measured by the Expanded Disability Status Scale (EDSS).ResultsThe prevalence of PRLs in BA patients with MS was higher at 55% compared to WA patients at 39% (p = 0.022). A higher percentage of PRLs among all white matter lesions was observed with BA (8.01%) patients compared to WA (3.4%) patients (p = 0.003). In a regression analysis, controlling for significant patient‐level covariates and income‐level demographics, the percentage of PRLs was, on average, 4.61 points higher for BA patients than for WA patients (p = 0.003). In a separate regression analysis, accounting for covariates, BA patients exhibited significantly higher EDSS scores (p < 0.001). Further analysis demonstrated that the percentage of PRLs was a mediator in the association between BA patients and greater disability (p = 0.031). Higher proportion of PRLs in BA population accounted for 14% of the total effect of race on disability.InterpretationBA patients exhibit greater disability, in part, due to their higher proportion of PRLs. This study underscores the substantial impact of chronic active lesions on disability outcomes in this specific minority MS patient population.
Dodecagonal GaN Microrods: Chemical Stability of a‐, m‐, and c‐Plane Walls and Their Application to Water‐Splitting
Authors: Janicki Łukasz , Gorantla Sandeep , Piskorska‐Hommel Edyta , Hommel Detlef , Kudrawiec Robert 
Published: September 2024

AbstractPhotoelectrolysis of water is a sustainable option for the production of hydrogen fuel. GaN nano‐ or microstructures are considered for water‐splitting due to their general high chemical stability and high surface‐to‐volume ratio enhancing the process effectiveness. In this study GaN structures with dodecagonal microrods are used as a working electrode for the water‐splitting process. Microrods are grown using a plasma‐assisted molecular beam epitaxy process allowing tailoring of microrod height and density. Their unique property is the of presence twelve sidewalls with alternating a‐ and m‐plane orientations. This enables a simultaneous study of the chemical stability of c‐, a‐, and m‐plane walls of GaN. The water‐splitting process is performed using a 1 mol l−1 NaOH electrolyte solution. Non‐zero current measured at zero bias under illumination indicates that the process takes place. A degradation of the GaN structure is observed after a prolonged process time. In short‐term exposures, etching of microrod sidewalls is observed. Roughening of the a‐plane walls studied by transmission electron microscopy indicates that this orientation is etched with a fastest rate. The internal crystalline structure is not influenced by the etching and remains stable as shown by the X‐ray absorption spectroscopy study.