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Over the course of evolution, many proteins have undergone adaptive structural changes to meet the increasing homeostatic regulatory demands of multicellularity. Aminoacyl tRNA synthetases (aaRS), enzymes that catalyze the attachment of each amino acid to its cognate tRNA, are such proteins that have acquired new domains and motifs that enable non-canonical functions. Through these new domains and motifs, aaRS can assemble into large, multi-subunit complexes that enhance the efficiency of many biological functions. Moreover, because the complexity of multi-aminoacyl tRNA synthetase (mARS) complexes increases with the corresponding complexity of higher eukaryotes, a contribution to regulation of homeostatic functions in multicellular organisms is hypothesized. While mARS complexes in lower eukaryotes may enhance efficiency of aminoacylation, little evidence exists to support a similar role in chordates or other higher eukaryotes. Rather, mARS complexes are reported to regulate multiple and variegated cellular processes that include angiogenesis, apoptosis, inflammation, anaphylaxis, and metabolism. Because all such processes are critical components of immune homeostasis, it is important to understand the role of mARS complexes in immune regulation. Here we provide a conceptual analysis of the current understanding of mARS complex dynamics and emerging mARS complex roles in immune regulation, the increased understanding of which should reveal therapeutic targets in immunity and immune-mediated disease.

IntroductionHookworms are parasitic helminths that secrete a variety of proteins that induce anti-inflammatory immune responses, stimulating increased CD4+Foxp3+ regulatory T cells and IL-10 production. Hookworm-derived recombinant proteins AIP-1 and AIP-2 have been shown to reduce inflammation in mouse models of inflammatory bowel disease and inflammatory airway disease by inducing CD4+Foxp3+ cells and IL-10 production. In contrast, chronic infection with the protozoal parasite Trypanosoma cruzi, the causative agent of Chagas disease, leads to chronic inflammation in tissues. Persistence of the parasites in tissues drives chronic low-grade inflammation, with increased infiltration of inflammatory cells into the heart, accompanied by increased production of inflammatory cytokines. There are no current antiparasitic drugs that effectively reduce or prevent chronic myocarditis caused by the onset of Chagas disease, thus new therapies are urgently needed. Therefore, the impact of AIP-1 and AIP-2 on myocarditis was investigated in a mouse model of chronic T. cruzi infection. MethodsFemale BALB/c mice infected with bioluminescent T. cruzi H1 strain trypomastigotes for 70 days were treated once daily for 7 days with 1mg/kg AIP-1 or AIP-2 protein by intraperitoneal injection. Control mice were left untreated or treated once daily for 14 days with 25mg/kg aspirin in drinking water. At 84 days of infection, splenocytes, cardiac tissue and serum were collected for evaluation. ResultsTreatment with both AIP-1 and AIP-2 proteins significantly reduced cardiac cellular infiltration, and reduced cardiac levels of IFNγ, IL-6 and IL-2. AIP-2 treatment reduced cardiac expression of COX-2. Further, while incubation with AIP-1 and AIP-2 proteins did not induce a significant upregulation of an immunoregulatory phenotype in dendritic cells (DC), there was a modest upregulation of CD11c+CD11b+MHCII+SIRPα+ expression, suggesting a regulatory phenotype. Ex-vivo stimulation of splenocytes from the treatment groups with AIP-1 loaded DC induced reduced levels of cytotoxic and pro-inflammatory T cells, stimulation with AIP-2 loaded DC specifically induced enhanced levels of CD4+CD25+Foxp3+ regulatory T cells among treatment groups. DiscussionAll in vivo and in vitro results demonstrate that hookworm-derived AIP-1 and AIP-2 proteins reduce T. cruzi induced cardiac inflammation, possibly through multiple anti-inflammatory mechanisms.

Background Interactions between immune and tumor cells are critical to determining cancer progression and response. In addition, preclinical prediction of immune-related drug efficacy is limited by interspecies differences between human and mouse, as well as inter-person germline and somatic variation. To address these gaps, we developed an autologous system that models the tumor microenvironment (TME) from individual patients with solid tumors.Method With patient-derived bone marrow hematopoietic stem and progenitor cells (HSPCs), we engrafted a patient’s hematopoietic system in MISTRG6 mice, followed by transfer of patient-derived xenograft (PDX) tissue, providing a fully genetically matched model to recapitulate the individual’s TME. We used this system to prospectively study tumor-immune interactions in patients with solid tumor.Results Autologous PDX mice generated innate and adaptive immune populations; these cells populated the TME; and tumors from autologously engrafted mice grew larger than tumors from non-engrafted littermate controls. Single-cell transcriptomics revealed a prominent vascular endothelial growth factor A (VEGFA) signature in TME myeloid cells, and inhibition of human VEGF-A abrogated enhanced growth.Conclusions Humanization of the interleukin 6 locus in MISTRG6 mice enhances HSPC engraftment, making it feasible to model tumor-immune interactions in an autologous manner from a bedside bone marrow aspirate. The TME from these autologous tumors display hallmarks of the human TME including innate and adaptive immune activation and provide a platform for preclinical drug testing.

Abstract Background Omental cysts are rare, predominantly occur in children, and often initially present with symptoms masquerading as other more common intra-abdominal pathologies. In this case report, we present the case of a child with an omental cyst that originated from the lesser sac. Due to the location of this cyst, resection presented unique technical challenges that have not been described in existing literature. Case presentation A 4-year-old male patient presented with symptoms initially concerning for appendicitis. Ultrasound showed a normal appendix but a large volume of complex intraperitoneal fluid. Computed tomography subsequently demonstrated a large cystic structure spanning from the stomach to the bladder. The patient was taken to the operating room where a large omental cyst was found to originate from the lesser sac. The resection was difficult due to the thin wall of the cyst and the intimate association of the superior-most aspect of the cyst with the tail of the pancreas, but was ultimately successful. Conclusions Omental cysts are rarely suspected before detection on abdominal imaging. Surgical resection is the treatment of choice, and complete resection can result in a recurrence-free postoperative course. Laparoscopic resection has been reported, but laparotomy is reasonable when a minimally invasive approach may not allow for a safe resection without rupture of the cyst. Anatomical characteristics of the cyst, as demonstrated in our case, can present challenges in the treatment of this otherwise benign entity.

Introduction Pituitary adenomas are a common intracranial pathology with an incidence of 15 to 20% in the population while cerebral aneurysms are less common with a prevalence of 1:50 patients. The incidence of aneurysms in patients with pituitary adenoma has been estimated at 2.3 to 5.4% of patients; however, this remains unclear. Equally, the management of concomitant lesions lacks significant understanding. Methods A case report is presented of a concomitant cerebral aneurysm and pituitary adenoma managed by minimally invasive endovascular and endoscopic methods, respectively. A systematic review of the literature for terms “pituitary adenoma” and “aneurysm” yielded 494 studies that were narrowed to 19 relevant articles. Results We report a case of a 67-year-old patient with an enlarging pituitary macroadenoma, cavernous carotid aneurysm, and unilateral carotid occlusion. After successful treatment of the aneurysm by a pipeline flow diverter, the pituitary adenoma was surgically resected by an endoscopic transsphenoidal approach. Conclusion The use of a pipeline flow diverter and endonasal approach was feasible in the treatment of our patient. This is the first report to our knowledge of the use of pipeline flow diversion in the management of a cavernous carotid aneurysm prior to pituitary adenoma treatment.

We report the case of a 69-year-old female who presented with a chronic nasal skin rash, new onset focal seizure, and a cerebral ring-enhancing lesion after a year of improper nasal irrigation. Despite aggressive and novel anti-amoebic treatment, she died as a result of a Balamuthia mandrillaris brain infection. Keywords: Amoeba, Balamuthia mandrillaris, Infectious encephalitis, Amoebic encephalitis, Nasal lavage

Carbon dots (C-dots) were facilely fabricated via a hydrothermal method and fully characterized. Our study shows that the as-synthesized C-dots are nontoxic, negatively charged spherical particles (average diameter 4.7 nm) with excellent water dispersion ability. Furthermore, the C-dots have a rich presence of surface functionalities such as hydroxyls and carboxyls as well as amines. The significance of the C-dots as highly efficient photocatalysts for rhodamine B (RhB) and methylene blue (MB) degradation was explored. The C-dots demonstrate excellent photocatalytic activity, achieving 100% of RhB and MB degradation within 170 min. The degradation rate constants for RhB and MB were 1.8 × 10−2 and 2.4 × 10−2 min−1, respectively. The photocatalytic degradation performances of the C-dots are comparable to those metal-based photocatalysts and generally better than previously reported C-dots photocatalysts. Collectively considering the excellent photocatalytic activity toward organic dye degradation, as well as the fact that they are facilely synthesized with no need of further doping, compositing, and tedious purification and separation, the C-dots fabricated in this work are demonstrated to be a promising alternative for pollutant degradation and environment protection.

AbstractModeling individual TRi-structural ISOtropic (TRISO) particles is possible using constructive solid geometry in Monte Carlo neutron transport codes (such as MCNP); however, the billions of surfaces required incurs considerable computational expense. Depletion simulations, in conjunction with Monte Carlo transport, are also inherently slow, requiring many individual criticality calculations to approximate time-dependent behavior. Additionally, choosing acceptable time step sizes, spatial zoning, and other depletion parameters involves prior knowledge and/or iteration by the user. The slow and complex nature of depletion calculations greatly increases the cost and duration of the design iteration process.The importance of tracked isotopes, spatial zones, and time stepping during depletion simulations is evaluated globally using neutron multiplication factor, total isotope inventory, and burnup. Different depletion schemes are compared using the TRISO-fueled Snowflake microreactor. Woodcock Delta Tracking and a Reactivity-equivalent Physical Transformation (RPT) are investigated as potential approaches to increase the speed of Monte Carlo neutron transport calculations involving TRISO fuel. The Monte Carlo N-Particle® Code (MCNP®) Version 6.3 is used to obtain the transport solution, and depletion calculations are performed using its internally coupled version of CINDER90. A prototype MCNP delta tracking module under development at Los Alamos National Laboratory is also used.Although a single spatial depletion region is sometimes acceptable, large errors in core lifetime and total 238Pu, 241Pu, and 242Pu mass are possible. The prototype delta tracking module significantly speeds up criticality calculations; however, depletion calculations are not always faster than those performed with surface tracking. The RPT method is effective at reducing CPU times in both criticality and depletion calculations, without significantly impacting neutron multiplication factor and total isotope inventory. The necessary number of time steps to converge total isotope inventory was also explored; the required number and spacing varied greatly depending on the objective of the depletion simulation. [ABSTRACT FROM AUTHOR]

The Black Hills State University Underground Campus (BHUC) houses a low background counting facility on the 4850' level of the Sanford Underground Research Facility. There are currently four ultra-low background, high-purity germanium detectors installed in the BHUC and it is anticipated four more detectors will be installed within a year. In total, the BHUC will be able to accommodate up to twelve detectors with space inside a class 1000 cleanroom, an automated liquid nitrogen fill system, on-site personnel assistance and other required utilities.

Over the course of evolution, many proteins have undergone adaptive structural changes to meet the increasing homeostatic regulatory demands of multicellularity. Aminoacyl tRNA synthetases (aaRS), enzymes that catalyze the attachment of each amino acid to its cognate tRNA, are such proteins that have acquired new domains and motifs that enable non-canonical functions. Through these new domains and motifs, aaRS can assemble into large, multi-subunit complexes that enhance the efficiency of many biological functions. Moreover, because the complexity of multi-aminoacyl tRNA synthetase (mARS) complexes increases with the corresponding complexity of higher eukaryotes, a contribution to regulation of homeostatic functions in multicellular organisms is hypothesized. While mARS complexes in lower eukaryotes may enhance efficiency of aminoacylation, little evidence exists to support a similar role in chordates or other higher eukaryotes. Rather, mARS complexes are reported to regulate multiple and variegated cellular processes that include angiogenesis, apoptosis, inflammation, anaphylaxis, and metabolism. Because all such processes are critical components of immune homeostasis, it is important to understand the role of mARS complexes in immune regulation. Here we provide a conceptual analysis of the current understanding of mARS complex dynamics and emerging mARS complex roles in immune regulation, the increased understanding of which should reveal therapeutic targets in immunity and immune-mediated disease. [ABSTRACT FROM AUTHOR]